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700 | 27,698,560 | CONCLUSION The effectiveness of domiciliary NIV remains uncertain ; however , some patients may benefit . | INTRODUCTION Noninvasive ventilation ( NIV ) improves survival among patients with hypercapnic respiratory failure in hospital , but evidence for its use in domiciliary setting s is limited .
A patient 's underlying risk of having an exacerbation may affect any potential benefit that can be gained from domiciliary NIV .
This is the first comprehensive systematic review to stratify patients based on a proxy for exacerbation risk : patients in a stable state and those immediately post-exacerbation hospitalization . | Background Chronic obstructive pulmonary disease ( COPD ) remains a significant public health burden . Non-invasive ventilation ( NIV ) is a method of supported breathing used as st and ard care for acutely unwell patients in hospital with COPD , but there is uncertainty around the potential benefits of using NIV in the treatment of stable patients in a non-hospital setting . This is a protocol for systematic review s of the clinical and cost-effectiveness of NIV in this context , being undertaken in support of a model based economic evaluation . Methods / Design St and ard systematic review methods aim ed at minimising bias will be employed for study identification , selection and data extraction for both the clinical and economic systematic review s. Bibliographic data bases ( for example MEDLINE , EMBASE ) and ongoing trials registers will be search ed from 1980 onwards . The search strategy will combine terms for the population with those for the intervention . Studies will be selected for review if the population includes adult patients with COPD and hypercapnic respiratory failure , however defined . Systematic review s , r and omised controlled trials and observational studies ( with n > 1 ) will be included , and quality assessment will be tailored to the different study design s. The primary outcome measures of interest are survival , quality of life , and healthcare utilisations ( hospitalisation and Accident and Emergency attendances ) . Meta-analyses will be undertaken where clinical and method ological homogeneity exists , supported by predefined subgroup analyses where appropriate . A systematic review of the evidence on the cost-effectiveness of non-hospital NIV will be completed , and a model-based cost-utility analysis undertaken to determine the cost-effectiveness of non-hospital-based NIV compared with st and ard care . Discussion These review s will attempt to clarify the clinical effectiveness of non-hospital NIV in COPD patients as well as the cost-effectiveness . The findings may indicate whether NIV in a non-hospital setting should be considered more routinely in this patient group , and what the likely cost implication s will be . PROSPERO registration 2012:CRD42012003286 Background Exacerbations of chronic obstructive pulmonary disease ( COPD ) are sporadic , acute worsening of symptoms . Identifying predictors of exacerbation frequency may facilitate medical interventions that reduce exacerbation frequency and severity . The objective of this study was to determine predictors of exacerbation frequency and mortality . Methods A total of 227 COPD patients were enrolled in a prospect i ve clinical study between January 2000 and December 2011 . Reported exacerbations were recorded for the year preceding enrollment and annually thereafter , and patients were grouped by median annual exacerbation frequency into those experiencing infrequent exacerbations ( less than one exacerbation annually ) and frequent exacerbations ( one or more exacerbation annually ) . Patients experiencing frequent exacerbations were further divided into those experiencing moderately frequent exacerbations ( fewer than two exacerbations per year ) and severely frequent exacerbations ( two or more exacerbations per year ) . The rate of clinical relapse and survival was recorded over a 10-year period . The mean of follow-up time was 5.15 years per patient . Results For patients experiencing infrequent , moderately frequent , and severely frequent exacerbations , median exacerbations in the year preceding enrollment were 0.0 , 0.5 , 1.0 , respectively , and more frequent exacerbations correlated with lower baseline forced expiratory volume in one second ( FEV1 ) ( 0.81 L , 0.75 L , and 0.66 L , respectively ) , higher comorbidity ( 70.7 % , 75.0 % , and 89.4 % , respectively ) , and greater NPPV use during hospitalization ( 16.4 % , 35.9 % and 51.1 % , respectively ) . FEV1 declined and mortality increased with increasing exacerbation frequency . Conclusions Exacerbation frequency can be used to generate discreet patient sub population s , supporting the hypothesis that multiple COPD phenotypes exist and can be used in patient risk stratification Background : Long-term non-invasive positive pressure ventilation ( NIPPV ) might improve the outcomes of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease ( COPD ) with chronic respiratory failure . A study was undertaken to investigate whether nocturnal NIPPV in addition to pulmonary rehabilitation improves health-related quality of life , functional status and gas exchange compared with pulmonary rehabilitation alone in patients with COPD with chronic hypercapnic respiratory failure . Methods : 72 patients with COPD were r and omly assigned to nocturnal NIPPV in addition to rehabilitation ( n = 37 ) or rehabilitation alone ( n = 35 ) . Outcome measures were assessed before and after the 3-month intervention period . Results : The Chronic Respiratory Question naire total score improved 15.1 points with NIPPV + rehabilitation compared with 8.7 points with rehabilitation alone . The difference of 7.5 points was not significant ( p = 0.08 ) . However , compared with rehabilitation alone , the difference in the fatigue domain was greater with NIPPV + rehabilitation ( mean difference 3.3 points , p<0.01 ) , as was the improvement in the Maugeri Respiratory Failure question naire total score ( mean difference −10 % , p<0.03 ) and its cognition domain ( mean difference −22 % , p<0.01 ) . Furthermore , the addition of NIPPV improved daytime arterial carbon dioxide pressure ( mean difference −0.3 kPa ; p<0.01 ) and daily step count ( mean difference 1269 steps/day , p<0.01 ) . This was accompanied by an increased daytime minute ventilation ( mean difference 1.4 l ; p<0.001 ) . Conclusion : Non-invasive ventilation augments the benefits of pulmonary rehabilitation in patients with COPD with chronic hypercapnic respiratory failure as it improves several measures of health-related quality of life , functional status and gas exchange . Trial registration number : NCT00135538 Introduction Noninvasive ventilation ( NIV ) is a well-established treatment for acute-on- chronic respiratory failure in hypercapnic COPD patients . Less is known about the effects of a long-term treatment with NIV in hypercapnic COPD patients and about the factors that may predict response in terms of improved oxygenation and lowered CO2 retention . Methods In this study , we r and omized 15 patients to a routine pharmacological treatment ( n = 5 , age 66 [ st and ard deviation ± 6 ] years , FEV1 30.5 [ ±5.1 ] % pred , PaO2 65 [ ±6 ] mmHg , PaCO2 52.4 [ ±6.0 ] mmHg ) or to a routine treatment and NIV ( using the Synchrony BiPAP device [ Respironics , Inc , Murrsville , PA ] ) ( n = 10 , age 65 [ ±7 ] years , FEV1 29.5 [ ±9.0 ] % pred , PaO2 59 [ ±13 ] mmHg , PaCO2 55.4 [ ±7.7 ] mmHg ) for 6 months . We looked at arterial blood gasses , lung function parameters and performed a low-dose computed tomography of the thorax , which was later used for segmentation ( providing lobe and airway volumes , iVlobe and iVaw ) and post-processing with computer methods ( providing airway resistance , iRaw ) giving overall a functional image of the separate airways and lobes . Results In both groups there was a nonsignificant change in FEV1 ( NIV group 29.5 [ 9.0 ] to 38.5 [ 14.6 ] % pred , control group 30.5 [ 5.1 ] to 36.8 [ 8.7 ] mmHg ) . PaCO2 dropped significantly only in the NIV group ( NIV : 55.4 [ 7.7 ] → 44.5 [ 4.70 ] , P = 0.0076 ; control : 52.4 [ 6.0 ] → 47.6 [ 8.2 ] , NS ) . Patients actively treated with NIV developed a more inhomogeneous redistribution of mass flow than control patients . Subsequent analysis indicated that in NIV-treated patients that improve their blood gases , mass flow was also redistributed towards areas with higher vessel density and less emphysema , indicating that flow was redistributed towards areas with better perfusion . There was a highly significant correlation between the % increase in mass flow towards lobes with a blood vessel density of > 9 % and the increase in PaO2 . Improved ventilation – perfusion match and recruitment of previously occluded small airways can explain the improvement in blood gases . Conclusion We can conclude that in hypercapnic COPD patients treated with long-term NIV over 6 months , a mass flow redistribution occurs , providing a better ventilation – perfusion match and hence better blood gases and lung function . Control patients improve homogeneously in iVaw and iRaw , without improvement in gas exchange since there is no improved ventilation/perfusion ratio or increased alveolar ventilation . These differences in response can be detected through functional imaging , which gives a more detailed report on regional lung volumes and resistances than classical lung function tests do . Possibly only patients with localized small airway disease are good c and i date s for long-term NIV treatment . To confirm this and to see if better arterial blood gases also lead to better health related quality of life and longer survival , we have to study a larger population Background : Sleep hypoventilation has been proposed as a cause of progressive hypercapnic respiratory failure and death in patients with severe chronic obstructive pulmonary disease ( COPD ) . A study was undertaken to determine the effects of nocturnal non-invasive bi-level pressure support ventilation ( NIV ) on survival , lung function and quality of life in patients with severe hypercapnic COPD . Method : A multicentre , open-label , r and omised controlled trial of NIV plus long-term oxygen therapy ( LTOT ) versus LTOT alone was performed in four Australian University Hospital sleep/respiratory medicine departments in patients with severe stable smoking-related COPD ( forced expiratory volume in 1 s ( FEV1.0 ) < 1.5 litres or < 50 % predicted and ratio of FEV1.0 to forced vital capacity ( FVC ) < 60 % with awake arterial carbon dioxide tension ( Paco2 ) > 46 mm Hg and on LTOT for at least 3 months ) and age < 80 years . Patients with sleep apnoea ( apnoea-hypopnoea index > 20/h ) or morbid obesity ( body mass index > 40 ) were excluded . Outcome measures were survival , spirometry , arterial blood gases , polysomnography , general and disease-specific quality of life and mood . Results : 144 patients were r and omised ( 72 to NIV + LTOT and 72 to LTOT alone ) . NIV improved sleep quality and sleep-related hypercapnia acutely , and patients complied well with therapy ( mean ( SD ) nightly use 4.5 ( 3.2 ) h ) . Compared with LTOT alone , NIV ( mean follow-up 2.21 years , range 0.01–5.59 ) showed an improvement in survival with the adjusted but not the unadjusted Cox model ( adjusted hazard ratio ( HR ) 0.63 , 95 % CI 0.40 to 0.99 , p = 0.045 ; unadjusted HR 0.82 , 95 % CI 0.53 to 1.25 , p = NS ) . FEV1.0 and Paco2 measured at 6 and 12 months were not different between groups . Patients assigned to NIV + LTOT had reduced general and mental health and vigour . Conclusions : Nocturnal NIV in stable oxygen-dependent patients with hypercapnic COPD may improve survival , but this appears to be at the cost of worsening quality of life . Trial registration number : The role of non-invasive nocturnal domiciliary ventilation ( NNV ) in chronic obstructive pulmonary disease ( COPD ) patients with chronic hypercapnia is still discussed . The aims of this study were to evaluate the long-term survival , the clinical effectiveness and side-effects of NNV in these patients . Forty-nine stable hypercapnic COPD patients on long-term oxygen therapy ( LTOT ) were assigned to two groups : in Group 1 , 28 patients performed NNV by pressure support modality in addition to LTOT ; in Group 2 , 21 patients continued their usual LTOT regimen . Treatment was assigned according to the compliance to NNV , after an in hospital period . Mortality rate , hospital stay ( HS ) and ICU admissions ( IA ) were recorded in the two groups . HS and IA were compared to those recorded in a similar period of follow-back . Lung and respiratory muscle function , dyspnoea , and exercise capacity ( by 6-min walk test ) were evaluated baseline and every 3 - 6 months up to 3 yr . Mean follow-up time was 35 + /- 7 months . Mortality rate was not different between the two groups : 16 , 33 , 46 % and 13 , 28 , 50 % at 1 , 2 and 3 yr in Groups 1 and 2 respectively . Lung and respiratory muscle function did not significantly change over time . A significant increase in 6-min walk test ( from 245 + /- 78 to 250 + /- 88 , 291 + /- 75 , 284 + /- 89 m after 1 , 2 and 3 yr respectively , P < 0.01 ) was observed only in patients undergoing NNV . In comparison to the follow back HS significantly decreased in both groups ( from 37 + /- 29 to 15 + /- 12 and from 32 + /- 18 to 17 + /- 11 days/pt/yr in Groups 1 and 2 respectively , P < 0.001 ) whereas IA significantly decreased only in patients performing also NNV ( from 1.0 + /- 0.7 to 0.2 + /- 0.3/pt/yr , P < 0.0001 ) . Addition of NNV by pressure support modality to LTOT does not improve long term survival but significantly reduces ICU admissions and improves exercise capacity in severe COPD with hypercapnia Background The use of domiciliary noninvasive positive pressure ventilation ( NPPV ) in stable chronic obstructive pulmonary disease ( COPD ) with chronic hypercapnic respiratory failure has yielded variable effects on survival , quality of life , and dyspnea . We hypothesized that use of NPPV in stable COPD and partial pressure of carbon dioxide ( PaCO2 ) < 52 mmHg might result in improvement in quality of life and dyspnea . Methods Thirty patients with stable COPD ( forced expiratory volume in the first second < 50 % predicted and PaCO2 < 52 mmHg ) were prospect ively r and omized to receive domiciliary NPPV ( bilevel positive airway pressure , 15/5 cm H2O ) or usual therapy for 6 months . Measurements were made at baseline , 6 weeks , 3 months , and 6 months . Primary outcomes were quality of life as assessed by the Chronic Respiratory Disease Question naire ( CRQ ) , and dyspnea as measured by the Transitional Dyspnea Index ( TDI ) . Results Fifteen subjects in the NPPV arm and 12 controls completed all the study visits . At 6 weeks and 3 months , the NPPV arm showed significant improvement in TDI total score . However , this effect persisted only in the TDI-Task at 6 months ( P=0.03 ) . NPPV use was associated with a small improvement in the CRQ-Mastery domain ( 0.6 versus −0.1 , P=0.04 ) . The arterial partial pressure of oxygen ( PaO2 ) in the control arm worsened over the period of the study , whereas it remained stable in the NPPV arm ( change −7.2 mmHg versus + 2.1 mmHg , respectively , P=0.02 ) . Conclusion NPPV result ed in a small improvement in quality of life indices in stable COPD patients with PaCO2 < 52 mmHg . Future larger studies will clarify the role of NPPV in this stable subgroup of patients with COPD Background : Patients with chronic obstructive pulmonary disease ( COPD ) pose a significant burden to healthcare providers with frequent exacerbations necessitating hospital admission . R and omised controlled data exist supporting the use of acute non-invasive ventilation ( NIV ) in patients with exacerbations of COPD with mild to moderate acidosis . The use of NIV is also described in chronic stable COPD , with evidence suggesting a reduction in hospital admissions and general practitioner care . We present economic data on the impact of domiciliary NIV on the need for admission to hospital and its attendant costs . Methods : A cost and consequences analysis of domiciliary NIV based on a before and after case note audit was performed in patients with recurrent acidotic exacerbations of COPD who tolerated and responded well to NIV . The primary outcome measure was the total cost incurred per patient per year from the perspective of the acute hospital . Effectiveness outcomes were total days in hospital and in intensive care . Results : Thirteen patients were identified . Provision of a home NIV service result ed in a mean ( 95 % CI ) saving of £ 8254 ( £ 4013 to £ 12 495 ) ( € 11 720 ; € 5698 to € 17 743 ) per patient per year . Total days in hospital fell from a mean ( SD ) of 78 ( 51 ) to 25 ( 25 ) ( p=0.004 ) , number of admissions from 5 ( 3 ) to 2 ( 2 ) ( p=0.007 ) , and ICU days fell from a total of 25 to 4 ( p=0.24 ) . Outpatient visits fell from a mean of 5 ( 3 ) to 4 ( 2 ) ( p=0.14 ) . Conclusions : This study suggests that domiciliary NIV for a highly selected group of COPD patients with recurrent admissions requiring NIV is effective at reducing admissions and minimises costs from the perspective of the acute hospital . Such evidence is important in obtaining financial support for providing such a service STUDY OBJECTIVES To determine the 1-year efficacy of noninvasive positive pressure ventilation ( NPPV ) added to long-term oxygen therapy ( LTOT ) in patients with stable severe COPD . PATIENT SELECTION AND METHODS : We prospect ively r and omized 52 patients with severe COPD ( FEV(1 ) < 45 % ) to either NPPV plus " st and ard care " ( 96 % patients with LTOT ) or to st and ard care alone ( 93 % patients with LTOT ) . The outcomes measured included the following : rate of acute COPD exacerbations ; hospital admissions ; intubations ; and mortality at 3 months , 6 months , and 12 months . The patients were also evaluated at 3 months and 6 months for dyspnea using the Medical Research Council and Borg scales , gas exchange , hematocrit , pulmonary function , cardiac function with echocardiogram , and neuropsychological performance . RESULTS One-year survival was similar in both groups ( 78 % ) . The number of acute exacerbations was similar at all time points in patients receiving NPPV , compared with control subjects . The number of hospital admissions was decreased at 3 months in the NPPV group ( 5 % vs 15 % of patients , p < 0.05 ) , but this difference was not seen at 6 months ( 18 % vs 19 % , respectively ) . The only beneficial differences were observed in the Borg dyspnea rating , which dropped from 6 to 5 ( p < 0.039 ) , and in one of the neuropsychological tests ( psychomotor coordination ) for the NPPV group at 6 months . CONCLUSIONS Our study indicates that over 1 year , NPPV does not affect the natural course of the disease and is of marginal benefit in out patients with severe COPD who are in stable condition ABSTRACT Recent r and omised controlled trials suggest non-invasive ventilation may offer benefit in the long-term management of ventilatory failure in stable COPD . The best mode of ventilation is unknown and newer volume assured modes may offer advantages by optimising ventilation overnight when treatment is delivered . This study compares volume assured with pressure preset non-invasive ventilation . R and omised crossover trial including twenty five subjects previously established on long-term non-invasive ventilation to manage COPD with chronic ventilatory failure . Two 8-week treatment periods of volume assured and pressure preset non-invasive ventilation . The primary outcomes were daytime arterial blood gas tensions and mean nocturnal oxygen saturation . Secondary outcomes included lung function , exercise capacity , mean nocturnal transcutaneous carbon dioxide , health status and compliance . No significant differences were seen in primary or secondary outcomes following 8 weeks of treatment when comparing volume assured and pressure preset ventilation . Primary outcomes assessed : mean ( st and ard deviation ) PaO2 7.8 ( 1.2 ) vs 8.1(1 ) kPa , PaCO2 6.7 ( 1.1 ) vs 6.3 ( 1.2 ) kPa and mean nocturnal oxygenation 90 ( 4 ) vs 91 (3)% volume assured versus pressure preset , respectively . Volume assured and pressure preset non-invasive ventilation appear equally effective in the long-term management of ventilatory failure associated with stable COPD Chronic obstructive pulmonary disease ( COPD ) patients with chronic ventilatory failure ( CVF ) are more likely to develop exacerbations , which are an important determinant of health-related quality of life ( HRQL ) . Long-term noninvasive positive-pressure ventilation ( NPPV ) has been proposed in addition to long-term oxygen therapy ( LTOT ) to treat CVF but little information is available on its effects on HRQL and re source consumption . Therefore , the current authors undertook a 2-yr multicentric , prospect i ve , r and omised , controlled trial to assess the effect of NPPV+LTOT on : 1 ) severity of hypercapnia ; 2 ) use of healthcare re sources , and 3 ) HRQL , in comparison with LTOT alone . One hundred and twenty-two stable hypercapnic COPD patients on LTOT for ≥6 months were consecutively enrolled . After inclusion and 1-month run-in , 90 patients were r and omly assigned to NPPV+LTOT ( n=43 ) or to LTOT alone ( n=47 ) . Arterial blood gases , hospital and intensive care unit ( ICU ) admissions , total hospital and ICU length of stay and HRQL were primary outcome measures ; survival and drop-out rates , symptoms ( dyspnoea and sleep quality ) and exercise tolerance were secondary outcome measures . Follow-up was performed at 3-month intervals up to 2 yrs . Lung function , inspiratory muscle function , exercise tolerance and sleep quality score did not change over time in either group . By contrast the carbon dioxide tension in arterial blood on usual oxygen , resting dyspnoea and HRQL , as assessed by the Maugeri Foundation Respiratory Failure Question naire , changed differently over time in the two groups in favour of NPPV+LTOT . Hospital admissions were not different between groups during the follow-up . Nevertheless , overall hospital admissions showed a different trend to change in the NPPV+LTOT ( decreasing by 45 % ) as compared with the LTOT group ( increasing by 27 % ) when comparing the follow-up with the follow-back periods . ICU stay decreased over time by 75 % and 20 % in the NPPV+LTOT and LTOT groups , respectively . Survival was similar . Compared with long-term oxygen therapy alone , the addition of noninvasive positive-pressure ventilation to long-term oxygen therapy in stable chronic obstructive pulmonary disease patients with chronic ventilatory failure : 1 ) slightly decreased the trend to carbon dioxide retention in patients receiving oxygen at home and 2 ) improved dyspnoea and health-related quality of life . The results of this study show some significant benefits with the use of nocturnal , home noninvasive positive-pressure ventilation in patients with chronic ventilatory failure due to advanced chronic obstructive pulmonary disease patients . Further work is required to evaluate the effect of noninvasive positive-pressure ventilation on reducing the frequency and severity of chronic obstructive pulmonary disease exacerbation Background High-intensity ( high-pressure and high backup rate ) noninvasive ventilation has recently been advocated for the management of stable hypercapnic chronic obstructive pulmonary disease ( COPD ) . However , the relative contributions of high inspiratory pressure and high backup rate to ventilator adherence and physiological outcome have not been investigated . Methods Patients with stable hypercapnic COPD ( daytime PaCO2 > 6 kPa ) and nocturnal hypoventilation were enrolled . Patients were r and omly allocated to high-pressure and high backup rate ( high-intensity ) and high-pressure and low backup rate ( high-pressure ) for a 6-week period . At the end of the first treatment period , patients were switched to the alternative treatment . The primary outcome measure was mean nightly ventilator usage . Results Twelve patients were recruited , with seven completing the 12-week trial protocol . The mean patient age was 71 ± 8 years , with a forced expiratory volume in one second (FEV1)/forced vital capacity ( FVC ) of 50 % ± 13 % and FEV1 of 32 % ± 12 % . The baseline PaCO2 and PaO2 were 8.6 ± 1.7 kPa and 7.3 ± 1.4 kPa , respectively . There was no significant difference demonstrated in mean nightly ventilator usage between the high-intensity and high-pressure groups ( difference of 4 minutes ; 95 % confidence interval −45 to 53 ; P = 0.9 ) . Furthermore , there were no differences in any of the secondary endpoints , with the exception of the respiratory domain of the Severe Respiratory Insufficiency question naire , which was lower in the high-intensity arm than in the high-pressure arm ( 57 ± 11 versus 69 ± 16 ; P < 0.05 ) . Conclusion There was no additional benefit , in terms of night-time ventilator adherence or any of the other measured parameters , demonstrated by addition of a high backup rate to high-pressure noninvasive ventilation . These data suggest that it is the high-pressure component of the high-intensity noninvasive ventilation approach that plays the important therapeutic role in the management of hypercapnic respiratory failure in COPD patients Background The use of noninvasive intermittent positive pressure ventilation ( NIPPV ) in chronic obstructive pulmonary disease ( COPD ) patients with chronic hypercapnic respiratory failure remains controversial as long-term data are almost lacking . The aim was to compare the outcome of 2-year home-based nocturnal NIPPV in addition to rehabilitation ( NIPPV + PR ) with rehabilitation alone ( PR ) in COPD patients with chronic hypercapnic respiratory failure . Methods Sixty-six patients could be analyzed for the two-year home-based follow-up period . Differences in change between the NIPPV + PR and PR group were assessed by a linear mixed effects model with a r and om effect on the intercept , and adjustment for baseline values . The primary outcome was health-related quality of life ( HRQoL ) ; secondary outcomes were mood state , dyspnea , gas exchange , functional status , pulmonary function , and exacerbation frequency . Results Although the addition of NIPPV did not significantly improve the Chronic Respiratory Question naire compared to rehabilitation alone ( mean difference in change between groups -1.3 points ( 95 % CI : -9.7 to 7.4 ) ) , the addition of NIPPV did improve HRQoL assessed with the Maugeri Respiratory Failure question naire ( -13.4 % ( -22.7 to -4.2 ; p = 0.005 ) ) , mood state ( Hospital Anxiety and Depression scale -4.0 points ( -7.8 to 0.0 ; p = 0.05 ) ) , dyspnea ( Medical Research Council -0.4 points ( -0.8 to -0.0 ; p = 0.05 ) ) , daytime arterial blood gases ( PaCO2 -0.4 kPa ( -0.8 to -0.2 ; p = 0.01 ) ; PaO2 0.8 kPa ( 0.0 to 1.5 ; p = 0.03 ) ) , 6-minute walking distance ( 77.3 m ( 46.4 to 108.0 ; p < 0.001 ) ) , Groningen Activity and Restriction scale ( -3.8 points ( -7.4 to -0.4 ; p = 0.03 ) ) , and forced expiratory volume in 1 second ( 115 ml ( 19 to 211 ; p = 0.019 ) ) . Exacerbation frequency was not changed . Conclusions The addition of NIPPV to pulmonary rehabilitation for 2 years in severe COPD patients with chronic hypercapnic respiratory failure improves HRQoL , mood , dyspnea , gas exchange , exercise tolerance and lung function decline . The benefits increase further with time . Trial registration Clinical Trials . Gov ( ID NCT00135538 ) Rationale The conventional approach of low-intensity non-invasive positive pressure ventilation ( NPPV ) produces only minimal physiological and clinical benefits in patients with stable hypercapnic chronic obstructive pulmonary disease ( COPD ) . Objectives To determine whether the novel approach of high-intensity NPPV is superior to low-intensity NPPV in controlling nocturnal hypoventilation . Methods A r and omised controlled crossover trial comparing 6 weeks of high-intensity NPPV ( using controlled ventilation with mean inspiratory pressures of 28.6±1.9 mbar ) with low-intensity NPPV ( using assisted ventilation with mean inspiratory pressures of 14.6±0.8 mbar ) was performed in 17 patients with severe stable hypercapnic COPD . Results Two patients refused low-intensity NPPV and two patients dropped out while on low-intensity NPPV . Thirteen patients ( mean forced expiratory volume in 1 s ( FEV1 ) 0.76±0.29 l ) completed the trial . High-intensity NPPV produced higher pneumotachographically-measured expiratory volumes , with a mean treatment effect of 96 ml ( 95 % CI 23 to 169 ) ( p=0.015 ) . This result ed in a mean treatment effect on nocturnal arterial carbon dioxide tension ( Paco2 ) of −9.2 mm Hg ( 95 % CI −13.7 to −4.6 ) ( p=0.001 ) in favour of high-intensity NPPV . Daily use of NPPV was increased in high-intensity NPPV compared with low-intensity NPPV , with a mean difference of 3.6 h/day ( 95 % CI 0.6 to 6.7 ) ( p=0.024 ) . In addition , compared with baseline , only high-intensity NPPV result ed in significant improvements in exercise-related dyspnoea , daytime Paco2 , FEV1 , vital capacity and the Severe Respiratory Insufficiency Question naire Summary Score . Conclusions High-intensity NPPV is better tolerated by patients with severe chronic hypercapnic COPD and has been shown to be superior to the conventional and widely-used form of low-intensity NPPV in controlling nocturnal hypoventilation . High-intensity NPPV therefore offers a new promising therapeutic option for these patients ABSTRACT Patients with ventilatory failure due to chronic obstructive pulmonary disease ( COPD ) are increasingly managed with long-term non-invasive positive pressure ventilation ( NIPPV ) and this may improve survival . NIPPV can frequently be interrupted but there are few data detailing the short-term effects and none on the longer-term consequences of treatment withdrawal . Ten patients withdrew from NIPPV for 1 week and were r and omised to restart NIPPV or to continued withdrawal for up to 6 months . Outcomes assessed included daytime blood gases , nocturnal ventilation , lung function , exercise capacity and health status . After 1 week of withdrawal PaO2 , PaCO2 , nocturnal oximetry , lung function and exercise capacity did not change , but mean nocturnal transcutaneous CO2 ( 6.3 ( 1 ) vs. 7.6 ( 1.1 ) kPa p = 0.04 ) and daytime blood gas bicarbonate ( 30.3 ( 4.5 ) vs. 31.2 ( 3.9 ) mmol/L p = 0.04 ) rose . During a 6-month period of withdrawal of nocturnal NIPPV , daytime PaCO2 ( 6 ( 1.1 ) vs. 7.5 ( 1.3 ) kPa p = 0.002 ) increased and health status ( total St George 's Respiratory Question naire score 55.5 ( 6.3 ) vs. 65.6 ( 10 ) p = 0.006 ) worsened . Three out of five patients met a priori criteria to restart NIPPV in the continued withdrawal group . Short interruptions to domiciliary NIPPV used to manage chronic ventilatory failure as a consequence of COPD do not cause a rapid clinical deterioration but nocturnal ventilation worsens and daytime bicarbonate levels increase following 1 week 's cessation . Thereafter , daytime PaCO2 rises and health status worsens , supporting the role of long-term NIPPV in the management of such patients In order to describe the outcomes of patients hospitalized with an acute exacerbation of severe chronic obstructive pulmonary disease ( COPD ) and determine the relationship between patient characteristics and length of survival , we studied a prospect i ve cohort of 1,016 adult patients from five hospitals who were admitted with an exacerbation of COPD and a PaCO2 of 50 mm Hg or more . Patient characteristics and acute physiology were determined . Outcomes were evaluated over a 6 mo period . Although only 11 % of the patients died during the index hospital stay , the 60-d , 180-d , 1-yr , and 2-yr mortality was high ( 20 % , 33 % , 43 % , and 49 % , respectively ) . The median cost of the index hospital stay was $ 7,100 ( $ 4,100 to $ 16,000 ; interquartile range ) . The median length of the index hospital stay was 9 d ( 5 to 15 d ) . After discharge , 446 patients were readmitted 754 times in the next 6 mo . At 6 mo , only 26 % of the cohort were both alive and able to report a good , very good , or excellent quality of life . Survival time was independently related to severity of illness , body mass index ( BMI ) , age , prior functional status , PaO2/FI(O2 ) , congestive heart failure , serum albumin , and the presence of cor pulmonale . Patients and caregivers should be aware of the likelihood of poor outcomes following hospitalization for exacerbation of COPD associated with hypercarbia The data on long-term application of non-invasive ventilation ( NIV ) in patients with chronic respiratory failure due to COPD are contradictory . We evaluated the effect of the addition of NIV to optimal treatment for 1 year on the quality of life of stable hypercapnic COPD patients . NIV was offered to 49 of 58 initially enrolled consecutive patients , of whom 22 refused NIV and comprised the st and ard treatment group whereas 27 received NIV . Quality of life was assessed with the SF-36 question naire . Additional measurements included blood gases , pulmonary function tests , dyspnea , daytime sleepiness , exacerbations and hospitalizations . The NIV group showed a significant improvement in quality of life in the third month , both in the Physical ( 31+/-4 to 38+/-8 , p<0.0001 ) and the Mental Component Summary Score ( 28+/-7 to 40+/-10 , p=0.009 ) , that was maintained until the twelfth month . PaCO2 decreased by the first month in the NIV group ( 54+/-4.5 to 44.6+/-5.6 mmHg , p<0.0001 ) , and PaO2 rose during the sixth month ( 58.9+/-5.7 to 64.4+/-6.5 mmHg , p=0.004 ) . Dyspnea and diurnal sleepiness improved significantly . No significant improvements were observed in the control group . Patients on NIV spent less days in the hospital compared to controls . NIV when added to optimal medical treatment has beneficial effects on quality of life in stable hypercapnic COPD patients , with additional improvements in arterial blood gases , dyspnea and daytime sleepiness BACKGROUND Evidence is weak for the ability of long-term non-invasive positive pressure ventilation ( NPPV ) to improve survival in patients with stable hypercapnic chronic obstructive pulmonary disease ( COPD ) . Previous prospect i ve studies did not target a reduction in hypercapnia when adjusting ventilator setting s. This study investigated the effect of long-term NPPV , targeted to markedly reduce hypercapnia , on survival in patients with advanced , stable hypercapnic COPD . METHODS This investigator-initiated , prospect i ve , multicentre , r and omised , controlled clinical trial enrolled patients with stable GOLD stage IV COPD and a partial carbon dioxide pressure ( PaCO2 ) of 7 kPa ( 51.9 mm Hg ) or higher and pH higher than 7.35 . NPPV was targeted to reduce baseline PaCO2 by at least 20 % or to achieve PaCO2 values lower than 6.5 kPa ( 48.1 mm Hg ) . Patients were r and omly assigned ( in a 1:1 ratio ) via a computer-generated r and omisation sequence with a block size of four , to continue optimised st and ard treatment ( control group ) or to receive additional NPPV for at least 12 months ( intervention group ) . The primary outcome was 1-year all-cause mortality . Analysis was by intention to treat . The intervention was unblinded , but outcome assessment was blinded to treatment assignment . This study is registered with Clinical Trials.gov , number NCT00710541 . FINDINGS Patients were recruited from 36 respiratory units in Germany and Austria , starting on Oct 29 , 2004 , and terminated with a record of the vital status on July 31 , 2011 . 195 patients were r and omly assigned to the NPPV group ( n=102 ) or to the control group ( n=93 ) . All patients from the control group and the NPPV group were included in the primary analysis . 1-year mortality was 12 % ( 12 of 102 patients ) in the intervention group and 33 % ( 31 of 93 patients ) in the control group ; hazard ratio 0.24 ( 95 % CI 0.11 - 0.49 ; p=0.0004 ) . 14 ( 14 % ) patients reported facial skin rash , which could be managed by changing the type of the mask . No other intervention-related adverse events were reported . INTERPRETATION The addition of long-term NPPV to st and ard treatment improves survival of patients with hypercapnic , stable COPD when NPPV is targeted to greatly reduce hypercapnia . FUNDING German Lung Foundation ; ResMed , Germany ; Tyco Healthcare , Germany ; and Weinmann , Germany OBJECTIVE To evaluate the efficacy and safety of home noninvasive positive pressure ventilation ( HNIPPV ) in hypercapnic patients with stable severe chronic obstructive pulmonary disease ( COPD ) . METHODS Forty four patients ( 30 males and 14 females , mean age 68.5 years ( range : 60 - 80 ) ) were recruited from a total of 106 patients with arterial PaCO2 ≥ 55 mm Hg in Second Hospital Affiliated to Harbin Medical University from January 2009 to December 2010 . Their clinical data were collected and analyzed . The patients in the HNIPPV group ( n = 20 ) accepted tiotropium bromide , doxofylline tablets and HNIPPV treatment while those in the control group ( n = 24 ) tiotropium bromide , doxofylline tablets and a low-flow inhalation of oxygen . The entire observation period was 6 months . The parameters before and after 6-month follow-up were compared , including lung function test , 6-min walking distance ( 6MWD ) , arterial blood gases ( PaO2 and PaCO2 ) , dyspnea grade , scores of emotional disorders and mean pulmonary artery pressure ( mPAP ) . RESULTS No significant difference existed in the baseline data between the HNIPPV and control groups . The forced expiratory volume in one second ( FEV(1 ) ) , forced vital capacity ( FVC ) , inspiratory capacity ( IC ) , 6MWD , PaO2 , PaCO2 , dyspnea grade , hospitalization rate , anxiety scores , depression scores and mPAP showed no significant difference between the HNIPPV and control groups before treatment . However , at Month 6 , the differences of IC , 6MWD , PaO2 , PaCO2 , dyspnea grade , anxiety scores , depression scores and mPAP in HNIPPV group ( ( 1.80 ± 0.14 ) L , ( 266 ± 24 ) m , ( 62.6 ± 4.6 ) mm Hg , ( 46.8 ± 2.2 ) mm Hg , ( 2.2 ± 0.5 ) , ( 6.5 ± 2.4 ) , ( 6.0 ± 1.6 ) , ( 33.8 ± 2.4 ) mm Hg ) were statistically significant compared with the control group ( ( 1.62 ± 0.14 ) L , ( 194 ± 23 ) m , ( 56.2 ± 3.8 ) mm Hg , ( 55.6 ± 3.0 ) mm Hg , ( 3.2 ± 0.6 ) , ( 10.6 ± 2.8 ) , ( 10.2 ± 2.4 ) , ( 36.6 ± 2.4 ) mm Hg ) ( P values : 0.031 , 0.018 , 0.025 , 0.026 , 0.001 , 0.013 , 0.002 , 0.014 respectively ) . FEV(1 ) and FVC in the HNIPPV group improved slightly but with no statistically significant difference ( all P > 0.05 ) . Two patients in the control group were taken to hospital because of acute exacerbation . And hospitalization rates increased in the control group . But no statistically significant difference existed between the HNIPPV and control groups ( P > 0.05 ) . The tolerance and compliance of HNIPPV in the HNIPPV group were better and the patients in the HNIPPV group had no pulmonary barotraumas . CONCLUSION HNIPPV plus tiotropium bromide and doxofylline tablets is both effective and safe in the treatment of hypercapnic patient with stable severe COPD PURPOSE Hypercapnia is regarded as a poor prognostic indicator in chronic obstructive pulmonary disease ( COPD ) , but many patients hospitalized with hypercapnia associated with an acute exacerbation of COPD revert to normocapnia during recovery . We wished to determine if this reversible hypercapnia represents a distinct pattern of respiratory failure in COPD , or simply a stage in the progression to chronic hypercapnia . We therefore compared the long-term clinical progression and survival of COPD patients with reversible hypercapnic respiratory failure ( defined as type 2.1 ) to those with normocapnic ( PaCO2 < 50 mm Hg ; type 1 ) and also to those patients with chronic hypercapnic ( PaCO2 > 50 mm Hg ) respiratory failure ( defined as type 2.2 ) . PATIENTS AND METHODS We prospect ively followed for 5 years a cohort of 85 patients who had been admitted as emergencies during a 1-year period to the respiratory unit of a University teaching hospital with an exacerbation of COPD complicated by respiratory failure ( PaO2 < 60 mm Hg ) . The main long-term outcome measures were survival and blood gas changes . RESULTS Sixty-eight ( 80 % ) patients survived the initial admission , and 17 ( 27 % ) survived 5 years . PaCO2 rose substantially more during exacerbations in type 2.1 patients ( mean 15.8 mm Hg ) , compared with type 2.2 ( mean 6.8 mm Hg ) and type 1 patients ( mean 1.5 mm Hg ) . We analyzed 149 subsequent admissions among the survivors over the following 5 years . Type 2.1 patients had a better 5-year survival ( 28 % ) than type 2.2 ( 11 % survival ; P < 0.05 ) , and similar to type 1 patients ( 33 % 5-year survival ) . Only 24 % of reversible hypercapnic patients developed chronic hypercapnia during long-term followup . CONCLUSIONS The data support reversible hypercapnia being a distinct manifestation of respiratory failure in COPD , with a similar prognosis to that of normocapnic respiratory failure AIMS The long-term benefit from noninvasive ventilation ( NIV ) in chronic hypercapnic chronic obstructive pulmonary disease ( COPD ) remains uncertain . METHODS Within a prospect i ve observational design , we compared the long-term survival of 140 patients with severe persistent hypercapnic COPD ( FEV(1 ) 28.7 + /- 8.7 % predicted ; PaCO(2 ) 60.1 + /- 9.2 mmHg ) with ( n = 99 ) or without ( n = 41 ) NIV . End-point was all-cause mortality , determined up to 4 years by Kaplan-Meier analysis . Additionally , Cox 's proportional hazards regression and stratification by risk factors was performed . Patients were characterised by anthropometric and functional parameters , comorbidities and medical therapy . RESULTS Adherence in patients with NIV was high ( 88.9 % ) , daily ventilator use being 6.4 + /- 2.6 h/day and inspiratory pressures 21.0 + /- 4.0 cmH(2)O. One- and 2-year survival rates were 87.7 % and 71.8 % , respectively , in patients with NIV vs. 56.7 % and 42.0 % in patients without NIV . Survival rates were significantly higher in patients with NIV compared to those without this therapy ( p = 0.001 ; hazard ratio 0.380 ; 95 % confidence interval 0.138 - 0.606 ) . The difference between groups was still significant after adjustment for differences in baseline characteristics . Moreover , stratification by risk factors revealed beneficial effects , particularly in patients with high base excess ( BE ; > 8.9 mmol/l ) , low pH ( < 7.41 ) , FEV(1 ) ( < 27.5 % ) haemoglobin ( < 13.8 g/dl ) or large hyperinflation ( residual volume-to-total lung capacity > 189 % predicted ) upon inclusion ( p < 0.05 each ) . CONCLUSION In patients with severe chronic hypercapnic COPD receiving NIV at high inspiratory pressure levels and showing high adherence to this therapy , long-term survival was significantly higher than in non-ventilated patients . Patients displaying more severe disease according to known risk factors seemed to benefit most from long-term NIV Intermittent positive pressure ventilation administered nocturnally via a nasal mask has been associated with improvements in pulmonary function and symptoms in patients with restrictive ventilatory disorders . We hypothesized that nocturnal nasal ventilation ( NNV ) would bring about similar improvements in patients with severe chronic obstructive pulmonary disease ( COPD ) . The study used a r and omized , crossover design , with subjects undergoing NNV or " st and ard care " for sequential 3-month periods . Of 23 patients with obstructive lung disease and a FEV1 less than 1 L who were initially enrolled , 4 were excluded because of obstructive sleep apnea prior to r and omization . Among the remaining 19 patients , 7 withdrew because of intolerance of the nose mask , 5 were withdrawn because of intercurrent illnesses , and 7 completed both arms of the protocol . These latter 7 patients used the ventilator for an average of 6.7 h/night , and 3 of the 7 had partial relief of dyspnea during ventilator use . However , in comparison with studies performed upon initiation or after the st and ard care arm of the study , studies performed after 3 months of NNV revealed no improvements in pulmonary function , respiratory muscle strength , gas exchange , exercise endurance , sleep efficiency , quality or oxygenation , or dyspnea ratings . The only improvements observed were in neuropsychological function , possibly related to a placebo effect or another unknown mechanism . Despite the small sample size , our study indicates that NNV is not well tolerated by and brings about minimal improvements in stable out patients with severe COPD The addition of noninvasive positive pressure ventilation ( NPPV ) to an exercise training ( ET ) program in severe chronic obstructive pulmonary disease ( COPD ) may produce greater benefits in exercise tolerance and quality of life than after training alone . Forty-five patients with severe stable COPD -mean ( SD ) FEV(1 ) 0.96 ( 0.31 ) L , Pa(O(2 ) ) 65.4 ( 9.07 ) mm Hg , Pa(CO(2 ) ) 45.6 ( 7.89 ) mm Hg-were r and omized to domiciliary NPPV + ET ( n = 23 ) or ET alone ( n = 22 ) . Exercise capacity and health status were assessed at baseline and after an 8-wk training program . There was a significant improvement in mean shuttle walk test ( SWT ) in the NPPV + ET group : from 169 ( 112 ) to 269 ( 124 ) m ( p = 0.001 ) , compared with the ET group : 205 ( 100 ) to 233 ( 123 ) m ( p = 0.19 ) ; mean difference ( 95 % confidence interval [ CI ] ) : 72 ( 12.9 to 131 ) m. Repeated measures analysis of variance ( ANOVA ) showed that the differences between the two groups became evident only in the final 4 wk of the training program with a mean end study difference ( 95 % 1CI ) of 65.8 ( 17.1 to 114 ) m. There was a significant improvement in the Chronic Respiratory Disease Question naire ( CRDQ ) of mean ( SD ) 24.0 ( 17.4 ) ( p = < 0.001 ) in the NPPV + ET group and 11.8 ( 15.8 ) ( p = 0.003 ) points in the ET group ; mean difference : 12.3 ( 1.19 to 23.4 ) . Only the NPPV + ET group demonstrated a significant improvement in arterial oxygenation ; mean difference : 3.70 mm Hg ( 0.37 to 7.27 ) . This study suggests that domiciliary NPPV can be used successfully to augment the effects of rehabilitation in severe COPD Non-invasive ventilation has been used in chronic respiratory failure due to chronic obstructive pulmonary disease ( COPD ) , but the effect of the addition of nasal positive-pressure ventilation to long-term oxygen therapy ( LTOT ) has not been determined . We report a r and omized crossover study of the effect of the combination of nasal pressure support ventilation ( NPSV ) and domiciliary LTOT as compared with LTOT alone in stable hypercapnic COPD . Fourteen patients were studied , with values ( mean + /- SD ) of Pao2 of 45.3 + /- 5.7 mm Hg , PaCO2 of 55.8 + /- 3.6 mm Hg , and FEV1 of 0.86 + /- 0.32 L. A 4 wk run-in period ( on usual therapy ) was followed by consecutive 3-mo periods of : ( 1 ) oxygen therapy alone , and ( 2 ) oxygen plus NPSV in r and omized order . Assessment s were made during run-in and at the end of each study period . There were significant improvements in daytime arterial PaO2 and PaCO2 , total sleep time , sleep efficiency , and overnight PaCO2 following 3 mo of oxygen plus NPSV as compared with run-in and oxygen alone . Quality of life with oxygen plus NPSV was significantly better than with oxygen alone . The degree of improvement in daytime PaCO2 was correlated with the improvement in mean overnight PaCO2 . Nasal positive-pressure ventilation may be a useful addition to LTOT in stable hypercapnic COPD BACKGROUND COPD patients who remain hypercapnic after acute respiratory failure requiring mechanical ventilation have a poor prognosis . Long-term nocturnal non-invasive ventilation ( NIV ) may be beneficial for these patients . We hypothesized that stable patients on long-term NIV would experience clinical worsening after withdrawal of NIV . METHODS We included 26 consecutive COPD patients ( 63 ± 6 years , 58 % male , FEV(1 ) 31 ± 14 % predicted ) who remained hypercapnic after acute respiratory failure requiring mechanical ventilation . After a six month run-in period , during which all patients received NIV , they were r and omised to either continue ( ventilation group , n = 13 ) or to stop NIV ( withdrawal group , n = 13 ) . The primary endpoint was time to clinical worsening defined as an escalation of mechanical ventilation . RESULTS All patients remained stable during the run-in period . After r and omisation the withdrawal group had a higher probability of clinical worsening compared to the ventilation group ( p = 0.0018 ) . After 12 months , ten patients ( 77 % ) in the withdrawal group , but only two patients ( 15 % ) in the ventilation group , experienced clinical worsening ( p = 0.0048 ) . Six-minute walking distance increased in the ventilation group . CONCLUSION COPD patients who remain hypercapnic after acute respiratory failure requiring mechanical ventilation may benefit from long-term NIV BACKGROUND AND OBJECTIVE Patients with COPD who require prolonged weaning from invasive mechanical ventilation show poor long-term survival . Whether non-invasive home mechanical ventilation ( HMV ) has a beneficial effect after prolonged weaning has not yet been clearly determined . METHODS Patients with COPD who required prolonged weaning and were admitted to a specialized weaning centre between January 2002 and February 2008 were enrolled in the study . Long-term survival and prognostic factors , including the role of non-invasive HMV , were evaluated . RESULTS Of 117 patients ( 87 men , 30 women ; mean age 69.5±9.5 years ) included in the study , weaning from invasive ventilation was achieved in 82 patients ( 70.1 % ) . Successful weaning was associated with better survival 1 year after discharge from hospital ( hazard ratio ( HR ) 2.24 , 95 % CI : 1.16 - 4.31 ; P=0.016 ) . Among the 82 patients who were successfully weaned , non-invasive HMV was initiated in 39 ( 47.6 % ) due to persistent chronic ventilatory failure . Initiation of HMV was associated with a higher rate of survival to 1 year as compared with patients who did not receive ventilatory support ( 84.2 % vs 54.3 % ; HR 3.68 , 95 % CI : 1.43 - 9.43 ; P=0.007 ) . In addition , younger age and higher PaO₂ , haemoglobin concentration and haematocrit at discharge were associated with better survival . In an adjusted multivariate analysis , initiation of non-invasive HMV after successful weaning remained an independent prognostic factor for survival to 1 year ( HR 3.63 , 95 % CI : 1.23 - 10.75 ; P=0.019 ) . CONCLUSIONS These findings suggest that based on the potential for improvement in long-term survival , non-invasive HMV should be considered in patients with severe COPD and persistent chronic hypercapnic respiratory failure after prolonged weaning Introduction The effectiveness of non-invasive positive pressure ventilation ( NIV ) in COPD patients with prolonged hypercapnia after ventilatory support for acute respiratory failure ( ARF ) remains unclear . We investigated if nocturnal NIV in these patients prolongs the time to readmission for respiratory causes or death ( primary endpoint ) in the following 12 months . Methods 201 COPD patients admitted to hospital with ARF and prolonged hypercapnia > 48 h after termination of ventilatory support were r and omised to NIV or st and ard treatment . Secondary outcomes were daytime arterial blood gasses , transcutaneous PCO2 during the night , lung function , health-related quality -of-life ( HRQL ) , mood state , daily activities and dyspnoea . Results 1 year after discharge , 65 % versus 64 % of patients ( NIV vs st and ard treatment ) were readmitted to hospital for respiratory causes or had died ; time to event was not different ( p=0.85 ) . Daytime PaCO2 was significantly improved in NIV versus st and ard treatment ( PaCO2 0.5 kPa ( 95 % CI 0.04 to 0.90 , p=0.03 ) ) as was transcutaneous PCO2 during the night . HRQL showed a trend ( p=0.054 , Severe Respiratory Insufficiency question naire ) in favour of NIV . Number of exacerbations , lung function , mood state , daily activity levels or dyspnoea was not significantly different . Discussion s We could not demonstrate an improvement in time to readmission or death by adding NIV for 1 year in patients with prolonged hypercapnia after an episode of NIV for ARF . There is no reason to believe the NIV was not effective since daytime PaCO2 and night-time PCO2 improved . The trend for improvement in HRQL favouring NIV we believe nevertheless should be explored further . Trial registration number NTR1100 BACKGROUND Patients with chronic obstructive pulmonary disease ( COPD ) who survive an episode of acute hypercapnic respiratory failure ( AHRF ) after treatment with non-invasive ventilation ( NIV ) have a high risk of recurrent AHRF . We hypothesised that continuation of NIV at home in these patients would reduce the likelihood of recurrent AHRF . METHODS A pilot prospect i ve r and omised controlled study was design ed to compare continuation of active home NIV and continuous positive airway pressure ( CPAP ) 5 cm H(2)O ( controls ) in COPD patients who had survived an episode of AHRF treated with acute NIV . Patients with significant obstructive sleep apnoea , non- COPD causes of AHRF , adverse psychosocial circumstances and serious comorbidities were excluded . The primary end-point was recurrent AHRF requiring acute NIV , intubation or result ing in death in the first year . RESULTS Twenty-three patients were r and omised to receive home NIV and 24 received CPAP . There was no significant difference in the baseline characteristics between the two study groups . The proportion of patients developing recurrent AHRF in the NIV and the CPAP groups was 38.5 % vs. 60.2 % at 1 year ( P = 0.039 ) . Four and eight patients , respectively , were withdrawn from the CPAP and NIV groups before the end of the pre-defined study duration . CONCLUSIONS In selected COPD patients with AHRF treated with acute NIV , continuation with home NIV is associated with a lower risk of recurrent severe COPD exacerbation with AHRF when compared with CPAP OBJECTIVE To evaluate the efficacy of nocturnal nasal ventilation ( NNV ) in patients with rigidly defined , severe but stable chronic obstructive pulmonary disease ( COPD ) and hypercapnia . DESIGN By r and omization , eligible patients were assigned to an active or a sham treatment arm . Data from these two groups were analyzed statistically . MATERIAL AND METHODS Initially , 35 patients with severe COPD ( forced expiratory volume in 1 second [ FEV1 ] of less than 40 % predicted ) and daytime hypercapnia ( arterial carbon dioxide tension [ PaCO2 ] of more than 45 mm Hg ) were enrolled in a 3-month NNV trial . After a minimal observation period of 6 weeks , 13 patients were judged to be clinical ly stable and were r and omized to NNV ( N = 7 ) or sham ( N = 6 ) treatment , consisting of nightly use of a bilevel positive airway pressure ( PAP ) device set to deliver an inspiratory pressure of either 10 or 0 cm of water ( H2O ) . The device was used in the spontaneous or timed mode and set to a minimal expiratory pressure of 2 cm H2O . Patients underwent extensive physiologic testing including polysomnography and were introduced to the bilevel PAP system during a 2.5-day hospital stay . RESULTS The NNV and sham treatment groups were similar in mean age ( 71.0 versus 66.5 years ) , PaCO2 ( 54.7 versus 48.5 mm Hg ) , and FEV1 ( 0.62 versus 0.72 L ) . Only four of seven patients in the NNV group were still using the bilevel PAP device at the completion of the trial , as opposed to all six patients in the sham group . Only one patient had a substantial reduction in PaCO2 - from 50 mm Hg at baseline to 43 mm Hg after 3 months of NNV . He declined further NNV treatment with bilevel PAP . Sham treatment did not lower PaCO2 . Lung function , nocturnal oxygen saturation , and sleep efficiency remained unchanged in both groups . CONCLUSION Disabled but clinical ly stable patients with COPD and hypercapnia do not readily accept and are unlikely to benefit from NNV BACKGROUND Cardiovascular comorbidities have a negative impact on the health status and prognosis of patients with COPD . We determined whether nocturnal noninvasive ( positive ) mechanical ventilation ( NIMV ) can improve heart rate variability ( HRV ) , decrease circulating natriuretic peptide levels , and improve functional performance of patients with very advanced COPD . METHODS A r and omized , double-blind , parallel controlled trial was conducted in 23 participants with stable but advanced COPD . Participants received st and ard medical therapy plus nocturnal NIMV or st and ard medical therapy plus sham NIMV for 3 months . RESULTS After 3 months of NIMV therapy , the 24-h triangular interpolation of N-N intervals increased from 322 to 473 ms ( p = 0.034 ) , the 24-h HRV index ( HRVI ) increased from 21.8 to 29.9 ms ( p = 0.035 ) , nocturnal HRVI increased from 6.1 to 8.0 ms ( p = 0.026 ) , and the SD of the average N-N interval increased from 37 to 41 ms ( p = 0.020 ) . None of these indexes changed significantly in the control group . Additionally , compared with the control group , the pro-atrial natriuretic peptide levels declined significantly in the NIMV group ( p = 0.013 ) . CONCLUSIONS NIMV applied nocturnally over 3 months may improve HRV , reduce circulating natriuretic peptide levels , and enhance the functional performance of patients with advanced but stable COPD . While not definitive due to small sample size , these data suggest that nocturnal NIMV may reduce the impact of cardiac comorbidities in COPD patients |
701 | 25,314,011 | For question 2 , first-line injectable agents ( ampicillin , gentamicin , and penicillin ) had low variable availability in first-level health facilities in Africa and South Asia .
Oral amoxicillin and cotrimoxazole were widely available at low cost in most regions .
Trained frontline health workers may screen for pBI in young infants with relatively high sensitivity and lower specificity .
Availability of first-line injectable antibiotics appears low in many health facilities in Africa and Asia . | BACKGROUND Inadequate illness recognition and access to antibiotics contribute to high case fatality from infections in young infants ( < 2 months ) in low- and middle-income countries ( LMICs ) .
We aim ed to address three questions regarding access to treatment for young infant infections in LMICs : ( 1 ) Can frontline health workers accurately diagnose possible bacterial infection ( pBI ) ? ; (
2 ) How available and affordable are antibiotics ? ; (
3 ) How often are antibiotics procured without a prescription ? | Aims : To provide a comprehensive description of young infant admissions to a first referral level health facility in Kenya . These data , currently lacking , are important given present efforts to st and ardise their care through the integrated management of childhood illness ( IMCI ) and for prioritising both health care provision and disease prevention strategies . Methods : Prospect i ve , 18 month observational study in a Kenyan district hospital of all admissions less than 3 months of age to the paediatric ward . Results : A total of 1080 infants were studied . Mortality was 18 % overall , though in those aged 0–7 days it was 34 % . Within two months of discharge a further 5 % of infants aged < 60 days on admission had died . Severe infection and prematurity together accounted for 57 % of inpatient deaths in those aged < 60 days , while jaundice and tetanus accounted for another 27 % . S pneumoniae , group B streptococcus , E coli , and Klebsiella spp . were the most common causes of invasive bacterial disease . Hypoxaemia , hypoglycaemia , and an inability to feed were each present in more than 20 % of infants aged 0–7 days . Both hypoxaemia and the inability to feed were associated with inpatient death ( OR 3.8 ( 95 % CI 2.5 to 5.8 ) and 7.4 ( 95 % CI 4.8 to 11.2 ) respectively ) . Conclusions : Young infants contribute substantially to paediatric inpatient mortality at the first referral level , highlighting the need both for basic supportive care facilities and improved disease prevention strategies OBJECTIVES To quantify the main reasons for referral of infants and children from first-level health facilities to referral hospitals in sub-Saharan Africa and to determine what further supplies , equipment , and legal empowerment might be needed to manage such children when referral is difficult . METHODS In an observational study at first-level health facilities in Ug and a , the United Republic of Tanzania , and Niger , over 3 - 5 months , we prospect ively documented the diagnoses and severity of diseases in children using the st and ardized Integrated Management of Childhood Illness ( IMCI ) guidelines . We review ed the facilities for supplies and equipment and examined the legal constraints of health personnel working at these facilities . FINDINGS We studied 7195 children aged 2 - 59 months , of whom 691 ( 9.6 % ) were classified under a severe IMCI classification that required urgent referral to a hospital . Overall , 226 children had general danger signs , 292 had severe pneumonia or very severe disease , 104 were severely dehydrated , 31 had severe persistent diarrhoea , 207 were severely malnourished , and 98 had severe anaemia . Considerably more ill were 415 young infants aged one week to two months : nearly three-quarters of these required referral . Legal constraints and a lack of simple equipment ( suction pumps , nebulizers , and oxygen concentrators ) and supplies ( nasogastric tubes and 50 % glucose ) could prevent health workers from dealing more appropriately with sick children when referral was not possible . CONCLUSION When referral is difficult or impossible , some additional supplies and equipment , as well as provision of simple guidelines , may improve management of seriously ill infants and children OBJECTIVE to estimate the prevalence and identify the determinants of non-prescription use of antibiotics for children in Mongolia . METHODS a community-based cross-sectional survey was undertaken in 10 subdistricts in Ulaanbaatar , Mongolia 's capital . We used a structured question naire to collect data from a r and om sample of 540 households with at least one child aged < 5 years . Logistic regression was used to identify factors associated with antibiotic misuse . FINDINGS of 503 participating caregivers , 71 % were mothers ; 42.3 % ( 95 % confidence interval , CI : 37.8 - 46.9 ) of caregivers had used non-prescribed antibiotics to treat symptoms in their child during the previous 6 months . Symptoms commonly treated were cough ( 84 % ) , fever ( 66 % ) , nasal discharge ( 65 % ) and sore throat ( 60 % ) . Amoxicillin was the most commonly used antibiotic ( 58 % ) . Pharmacies were the main source ( 86 % ) of non-prescribed antibiotics . Non-prescribed use by mothers was significantly associated with keeping antibiotics at home ( odds ratio , OR : 1.7 ; 95 % CI : 1.04 - 2.79 ) , caregiver self-medication ( OR : 6.3 ; 95 % CI : 3.8 - 10.5 ) and older child 's age ( OR : 1.02 ; 95 % CI : 1.01 - 1.04 ) . Caregivers with a better knowledge of antibiotics were less likely to give children non-prescribed antibiotics ( OR : 0.7 ; 95 % CI : 0.6 - 0.8 ) . CONCLUSION the prevalence of non-prescribed antibiotic use for young children was high in Ulaanbaatar . Because such use leads to the spread of bacterial resistance to antibiotics and related health problems , our findings have important implication s for public education and the enforcement of regulations regarding the sale of antibiotics in Mongolia Background : In re source -limited setting s , most young infants with signs of severe infection do not receive the recommended inpatient treatment with intravenous broad spectrum antibiotics for 10 days or more because such treatment is not accessible , acceptable or affordable to families . This trial was initiated in the Democratic Republic of Congo , Kenya and Nigeria to assess the safety and efficacy of simplified treatment regimens for the young infants with signs of severe infection who can not receive hospital care . Methods : This is a r and omized , open-label equivalence trial in which 3600 young infants with signs of clinical severe infection will be enrolled . The primary outcome is treatment failure in 7 days after enrollment , which includes death or worsening of the clinical condition on any day , or no improvement in the clinical condition by day 4 of treatment . Secondary outcomes include compliance with study therapy , adverse effects due to the study drugs and relapse or death during the week after completion of treatment . Discussion : The results of this study , along with ongoing studies in Pakistan and Bangladesh , will inform the development of global policy for treatment of severe neonatal infections in re source -limited setting OBJECTIVE Little data has been published on the presenting symptoms and signs among ill infants aged < 60 days from developing countries . We aim ed to describe and evaluate the potential of simple clinical features to identify severe illness among young infants who present to rural district hospitals in Kenya . METHODS St and ardized assessment tools were design ed to record clinical symptoms and signs . Data were collected prospect ively on all infants aged < 60 days who weighed > or = 1.5 kg and were admitted over an 18-month period . The same data were collected , prospect ively from infants recruited to a contemporaneous hospital birth cohort who became ill and were assessed and treated as out patients at the same hospital . FINDINGS Data on 467 outpatient consultations and 769 inpatient episodes were available for analysis . These data highlighted the importance of findings in the history , particularly breathing difficulties , abnormal feeding , and abnormal behaviour , as well as clinical signs in the evaluation of young infants . They indicated possible important differences in the panel of signs useful for detecting severe illness in infants aged 0 - 6 days and those aged 7 - 59 days . They also showed that some simplification of current guidelines that still preserved the sensitivity and specificity for detecting very severe disease might be possible . CONCLUSION Simple clinical features may allow distinction between severe and non-severe illness to be made with reasonable confidence . Prospect i ve studies on an adequate scale are needed urgently to provide current integrated management of childhood illness guidelines for young infants with an adequate evidence base To determine the effect of antibiotic formulations on compliance , 400 children , aged 2 months to 5 years , with a presumptive diagnosis of pneumonia , were r and omly assigned to receive one of the following formulations of cotrimoxazole : 1 . syrup accompanied by a 10-ml measuring cup ; 2 . syrup accompanied by a 5-ml measuring spoon ; 3 . tablets ; 4 . single-dose sachets of antibiotic powder . A research assistant visited the childs ' home on the fourth day of therapy , asked the care-giver about compliance , and observed the care-giver prepare a dose of the medication . The remaining amount of medicine was measured , and when possible ( n = 151 ) , a urine specimen was tested for the presence of sulphamethoxazole . All of the care-givers reported giving at least one dose on the first day of therapy . By the fourth day , 82 per cent of those receiving syrup were still taking their medication compared to 71 and 55 per cent of those receiving sachets or tablets , respectively ( P < 0.01 ) . Of those who received syrup accompanied by a spoon , 38 per cent under-dosed the medicine by at least 30 per cent . Overall , compliance was highly correlated with the care-giver 's report of difficulty in administering the medication . Additional research is needed to underst and the obstacles encountered by care-givers in administering sachets and tablets . Meanwhile , the use of antibiotic syrup , accompanied by an appropriately sized measuring cup , appears to offer the greatest probability of medication compliance in the treatment of Egyptian children with pneumonia Objective To check the validity of Integrated Management of Neonatal and Childhood Illness ( IMNCI ) algorithm for young infants ( 0–2 months ) . Design Prospect i ve observational study . Setting The outpatient department and emergency room of a medical college attached hospital . Methods 419 infants ( 176 between 0–7 days , 243 between 7 days-2 months ) underwent a detailed diagnostic assessment and treatment as per the st and ard protocol of treating unit . These infants also underwent assessment , classification and identification of treatment as per IMNCI algorithm . The diagnostic and therapeutic agreement between st and ard protocol and IMNCI was computed to assess the validity of IMNCI algorithm . Results The IMNCI algorithm performed well in identifying sick young infants with sensitivity of 97 % , 94 % and 95 % , and specificity of 85 % , 87 % and 87 % in 0–7 days , 7 days-2 months and 0–2 months age groups , respectively . The algorithm covered majority ( 80 % ) of recorded diagnoses , and could identify bacterial infection with 88.5 % sensitivity and 57.4 % specificity . Complete diagnostic agreement with gold st and ard was seen in 50 % ; overdiagnosis and under diagnosis was seen in 13 % and 19 % , respectively . Low birthweight and upper respiratory infection were the main reasons for overdiagnosis whereas surgical conditions result ed in under diagnoses in majority . Conclusion IMNCI algorithm for evaluation and management of young infants has good sensitivity and specificity for referring cases with severe illness Antibiotics are utilized excessively in many areas of the world . To better define how often and why these drugs are used , we prospect ively studied antibiotic use among a cohort of 105 children less than five years of age in a poor area of the northeastern Brazilian city of Fortaleza . During a 16-week period , 65 children took 137 courses of antibiotics . Physicians recommended 54 % of these , mothers or their associates 39 % , and pharmacy workers 7 % . Mothers and pharmacy workers recommended drugs for shorter courses than physicians , and were more likely to recommend drugs inappropriate for children . Duration of illness was not a risk factor for antibiotic use , but both poor nutritional status and poor socioeconomic status were . Health care seeking behaviour was further studied in 58 diarrhoea episodes . The type of care sought was related to the duration of illness . Overall , antibiotic use was very common and often inappropriate among children in this poor urban area . More controlled use might decrease the use of potentially dangerous drugs and the use of these drugs when no benefit is likely BACKGROUND About 500,000 sepsis-related deaths per year arise in the first 3 days of life . On the basis of results from non-r and omised studies , use of vaginal chlorhexidine wipes during labour has been proposed as an intervention for the prevention of early-onset neonatal sepsis in developing countries . We therefore assessed the efficacy of chlorhexidine in early-onset neonatal sepsis and vertical transmission of group B streptococcus . METHODS In a trial in Soweto , South Africa , 8011 women ( aged 12 - 51 years ) were r and omly assigned in a 1:1 ratio to chlorhexidine vaginal wipes or external genitalia water wipes during active labour , and their 8129 newborn babies were assigned to full-body ( intervention group ) or foot ( control group ) washes with chlorhexidine at birth , respectively . In a subset of mothers ( n=5144 ) , we gathered maternal lower vaginal swabs and neonatal skin swabs after delivery to assess colonisation with potentially pathogenic bacteria . Primary outcomes were neonatal sepsis in the first 3 days of life and vertical transmission of group B streptococcus . Analysis was by intention to treat . The trial is registered with Clinical Trials.gov , number NCT00136370 . FINDINGS Rates of neonatal sepsis did not differ between the groups ( chlorhexidine 141 [ 3 % ] of 4072 vs control 148 [ 4 % ] of 4057 ; p=0.6518 ) . Rates of colonisation with group B streptococcus in newborn babies born to mothers in the chlorhexidine ( 217 [ 54 % ] of 401 ) and control groups ( 234 [ 55 % ] of 429 ] did not differ ( efficacy -0.05 % , 95 % CI -9.5 to 7.9 ) . INTERPRETATION Because chlorhexidine intravaginal and neonatal wipes did not prevent neonatal sepsis or the vertical acquisition of potentially pathogenic bacteria among neonates , we need other interventions to reduce childhood mortality . FUNDING US Agency for International Development , National Vaccine Program Office and Centers for Disease Control 's Antimicrobial Resistance Working Group , and Bill & Melinda Gates Foundation Background : Sepsis in the neonatal period is a major cause of child mortality in low-income countries . Hospitalization and parenteral penicillin/ampicillin and gentamicin therapy are recommended for management . Many families , however , are unable to access hospital care , and most home-delivered newborns who develop sepsis die without receiving antibiotic therapy . Appropriate community-based therapy in such situations is undefined . We compared failure rates of 3 clinic-based antibiotic regimens in 0- to 59-day-old infants with possible serious bacterial infection whose families refused hospitalization in Karachi communities with high neonatal mortality rates > 45/1000 live births . Methods : Eligible infants were r and omly assigned to 7 days of : ( 1 ) procaine penicillin [ 50,000 units/kg once daily ( OD ) by intramuscular injection ( IM ) ] and gentamicin ( 5 mg/kg OD IM ) reference arm , ( 2 ) ceftriaxone ( 50 mg/kg OD IM ) , or ( 3 ) oral trimethoprim-sulfamethoxazole ( TMP-SMX ) at 10 mg/kg/day divided twice daily and gentamicin IM OD . Primary outcome was treatment failure , defined as death , deterioration in clinical condition during therapy or no improvement after 2 days . Results : Possible serious bacterial infection was diagnosed in 704 infants , among 5766 screened . Among 434 ( 61.6 % ) r and omized to clinic-based therapy , there were 13 of 145 failures with penicillin-gentamicin , 22 of 145 with ceftriaxone and 26 of 143 with TMP-SMX-gentamicin . Treatment failure was significantly higher with TMP-SMX-gentamicin compared with penicillin-gentamicin [ relative risk 2.03 , 95 % confidence interval : 1.09 – 3.79 ] by intention-to-treat analysis . Differences were not significant in the ceftriaxone versus penicillin-gentamicin comparison [ relative risk 1.69 , 95 % confidence interval 0.89–3.23 ) . By 14 days , there were 2 deaths in the penicillin-gentamicin group , 3 in the ceftriaxone group and 11 in the TMP-SMX-gentamicin group [ relative risk 5.58 , 95 % confidence interval : 1.26–24.72 ( group 3 versus 1 ) ] . Conclusion : When hospitalization of sick infants is unfeasible , outpatient therapy with injectable antibiotics is an effective option . Procaine penicillin-gentamicin was superior to TMP-SMX-gentamicin . Ceftriaxone is a more expensive option , and may be less effective , although this requires further research Background : Infections account for about half of neonatal deaths in low-re source setting s. Limited evidence supports home-based treatment of newborn infections by community health workers ( CHW ) . Methods : In one study arm of a cluster r and omized controlled trial , CHWs assessed neonates at home , using a 20-sign clinical algorithm and classified sick neonates as having very severe disease or possible very severe disease . Over a 2-year period , 10,585 live births were recorded in the study area . CHWs assessed 8474 ( 80 % ) of the neonates within the first week of life and referred neonates with signs of severe disease . If referral failed but parents consented to home treatment , CHWs treated neonates with very severe disease or possible very severe disease with multiple signs , using injectable antibiotics . Results : For very severe disease , referral compliance was 34 % ( 162/478 cases ) , and home treatment acceptance was 43 % ( 204/478 cases ) . The case fatality rate was 4.4 % ( 9/204 ) for CHW treatment , 14.2 % ( 23/162 ) for treatment by qualified medical providers , and 28.5 % ( 32/112 ) for those who received no treatment or who were treated by other unqualified providers . After controlling for differences in background characteristics and illness signs among treatment groups , newborns treated by CHWs had a hazard ratio of 0.22 ( 95 % confidence interval [ CI ] = 0.07–0.71 ) for death during the neonatal period and those treated by qualified providers had a hazard ratio of 0.61 ( 95 % CI = 0.37–0.99 ) , compared with newborns who received no treatment or were treated by untrained providers . Significantly increased hazards ratios of death were observed for neonates with convulsions ( hazard ratio [ HR ] = 6.54 ; 95 % CI = 3.98–10.76 ) , chest in-drawing ( HR = 2.38 , 95 % CI = 1.29–4.39 ) , temperature < 35.3 ° C ( HR = 3.47 , 95 % CI = 1.30–9.24 ) , and unconsciousness ( HR = 7.92 , 95 % CI = 3.13–20.04 ) . Conclusions : Home treatment of very severe disease in neonates by CHWs was effective and acceptable in a low-re source setting in Bangladesh Ninety-nine cases of neonatal septicaemia prospect ively seen over a 3-year period in a large cosmopolitan African city of high altitude is presented . An incidence of 6.5 per 1000 live births was noted . Though the most important pathogens were Klebsiella spp . and Staphylococcus aureus , Citrobacter difficile and Alkalegenes faecalis were the pathogens associated with a high mortality rate . Low birth weight infants were significantly more affected . The overall mortality rate was 27.3 per cent . The commonest predisposing perinatal factors were birth asphyxia and prolonged rupture of fetal membranes . On the basis of the trend of organisms isolated and their sensitivity pattern , it is suggested that the initial use of gentamicin alone is satisfactory OBJECTIVE To estimate the validity ( sensitivity , specificity , and positive and negative predictive values ) of a clinical algorithm as used by community health workers ( CHWs ) to detect and classify neonatal illness during routine household visits in rural Bangladesh . METHODS CHWs evaluated breastfeeding and symptoms and signs of illness in 395 neonates selected r and omly from neonatal illness surveillance during household visits on postnatal days 0 , 2 , 5 and 8 . Neonates classified with very severe disease ( VSD ) were referred to a community-based hospital . Within 12 hours of CHW assessment s , physicians independently evaluated all neonates seen in a given day by one CHW , r and omly chosen from among 36 project CHWs . Physicians recorded symptoms and signs of illness , classified the illness , and determined whether the newborn needed referral-level care at the hospital . Physicians ' identification and classification were used as the gold st and ard in determining the validity of CHWs ' identification of symptoms and signs of illness and its classification . FINDINGS CHWs ' classification of VSD showed a sensitivity of 73 % , a specificity of 98 % , a positive predictive value of 57 % and a negative predictive value of 99 % . A maternal report of any feeding problem as ascertained by physician question ing was significantly associated ( P < 0.001 ) with ' not sucking at all ' and ' not attached at all ' or ' not well attached ' as determined clinical ly by CHWs during feeding assessment . CONCLUSION CHWs identified with high validity the neonates with severe illness needing referral-level care . Home-based illness recognition and management , including referral of neonates with severe illness by CHWs , is a promising strategy for improving neonatal health and survival in low-re source developing country setting OBJECTIVE To evaluate simple clinical signs of illness in young infants ( 0 to 2 months ) and to correlate with WHO IMCI algorithm ( 7 days-2 months ) . DESIGN Prospect i ve observational . Study conducted in the outpatient department and emergency room of a pediatric tertiary level hospital . METHODS Four hundred and ninety seven young infants ( 0 to 2 months ) presenting to outpatient department or emergency room were recruited . Detailed history , clinical examination including all signs in IMCI algorithm was recorded in the pre- design ed proforma . The study subjects were investigated and managed according to the protocol of treating unit , which served as gold st and ard . The diagnostic and therapeutic agreement between the gold st and ard and IMCI was computed . The study subjects were analyzed as one age group ( 0 to 2 months ) and also after de- segregating into early and late neonatal age group ( 0 to 7 days and 7 days to 2 months age ) . RESULTS Mean number of illnesses in 0 to 7 days , 7 days-2 months and 0 - 2 months groups were 1.97 , 2.0 and 2.02 respectively . Those who required referral as per IMCI algorithm had higher proportion of co-morbidities . The referral criteria were fairly sensitive ( 78 to 85 percent ) in predicting hospitalization with moderately high specificity ( 78 percent ) . Diagnostic agreement between gold st and ard and IMCI module was complete in 57 to 68 percent . Amongst diagnostic mismatch , under-diagnosis was found more frequently ( 72 to 82 percent ) than over-diagnosis ( 17 to 29 percent ) . The sensitivity of algorithm to identify serious bacterial infections was quite high ( 96 to 98 percent ) with moderately good specificity ( 80 to 92 percent ) . Jaundice was single most important complaint accounting for 47 to 62 percent of diagnostic mismatch . CONCLUSION IMCI algorithm appears to be a promising , feasible and useful intervention strategy to triage and treat young infants in 7 days-2 months age group . This tool remains effective even when extended to 0 to 7 days age group . However a further increase in its sensitivity can be achieved by including yellowness of lower extremities/ palms/ soles as a criterion BACKGROUND Majority of the neonates in developing countries are born and cared for in rural homes but the available information is mostly hospital based . OBJECTIVES To estimate : ( i ) the incidence of various neonatal morbidities and associated case fatality in home-cared rural neonates , ( ii ) proportion of neonates with indications for health care , and ( iii ) the proportion who actually receive it . DESIGN Prospect i ve observational study . SETTING Rural homes . METHODS Neonates in 39 study villages in the Gadchiroli district ( Maharashtra , India ) were observed during one year ( 1995 - 96 ) by 39 trained female village health workers at birth and during neonatal period ( 0 - 28 days ) by making eight home visits . A physician checked the data and the morbidities were diagnosed by a computer program . Vital statistics in these villages was independently collected . RESULTS Out of 1016 live births , 95 % occurred at home and 763 ( 75&% ) neonates were observed . The agreement between observations by health workers and physician was 92 % . Total 48.2 & neonates suffered high risk morbidities ( associated case fatality > 10 % ) , 72.2 % suffered low risk morbidities , and 17.9 % gained inadequate weight ( less than 300 g ) . Seventeen percent neonates developed clinical picture suggestive of sepsis . Though 54.4 % neonates had indications for health care and 38 out of total 40 neonatal deaths occurred in these , only 2.6 % received medical attention . The neonatal mortality rate was 52.4/1000 live births . CONCLUSION Nearly half of the neonates in rural homes developed high risk morbidities ten times the neonatal morbidity rate and needed health care but practically none received it . The magnitude of care gap suggests an urgent need for developing home-based neonatal care to reduce neonatal morbidities and OBJECTIVE To determine the prevalence of self-medication in children and adolescents in the municipalities of Limeira and Piracicaba , state of São Paulo , and to correlate results with sociodemographic indicators and with the use of health care services ( public or private ) . METHODS Descriptive population -based study of a simple r and om sample from the two municipalities , comprised of 772 inhabitants from 85 urban census sectors selected through cluster sampling . INCLUSION CRITERIA age < or = 18 years ; interview with one parent/tutor ; consumption of at least one drug in the previous 15 days . Subjects were divided into two study groups according to their pattern of drug use : self-medication ( lay advice ) and medical prescription . Linear association tests , descriptive analysis of variables and multiple logistic regression tests were carried out to analyze data . RESULTS The prevalence of self-medication was 56.6 % . Mothers ( 51 % ) and drugstore employees ( 20.1 % ) were most frequently responsible for self-medication . The main groups of self-prescribed drugs were : analgesic/antipyretic and non-hormonal anti-inflammatory drugs ( 52.9 % ) ; drugs acting on the respiratory tract ( 15.4 % ) and gastrointestinal drugs ( 9.6 % ) ; and systemic antibiotics ( 8.6 % ) . The situation that most commonly motivated self-medication were respiratory diseases ( 17.2 % ) , fever ( 15 % ) , and headache ( 14 % ) . Subjects in the age group of 7 - 18 years ( odds ratio = 2.81 ) and public health care users ( odds ratio = 1.52 ) showed increased risk for self-medication . CONCLUSIONS The prevalence of self-medication in children and adolescents was high , which reinforces the need for public health interventions aim ing at preventing this practice The object of this study was to evaluate and improve the guidelines for the Integrated Management of Childhood Illness ( IMCI ) with respect to identifying young infants and children requiring referral to hospital in an area of low malaria prevalence . A total of 234 young infants ( aged 1 week to 2 months ) and 668 children ( aged 2 months to 5 years ) were prospect ively sample d from patients presenting at a children 's hospital in Dhaka , Bangladesh . The study paediatricians obtained a st and ardized history and carried out a physical examination , including items in the IMCI guidelines developed by WHO and UNICEF . The paediatricians made a provisional diagnosis and judged whether each patient needed hospital admission . Using the paediatrician 's assessment of a need for admission as the st and ard , the sensitivity and specificity of the current and modified IMCI guidelines for correctly referring patients to hospital were examined . The IMCI 's sensitivity for a paediatrician 's assessment in favour of hospital admission was 84 % ( 95 % confidence interval ( CI ) : 75 - 90 ) for young infants and 86 % ( 95 % CI : 81 - 90 ) for children , and the specificity was , respectively , 54 % ( 95 % CI : 45 - 63 ) and 64 % ( 95 % CI : 59 - 69 ) . One fourth or more in each group had a provisional diagnosis of pneumonia , and the IMCI 's specificity was increased without lowering sensitivity by modifying the respiratory signs calling for referral . These results show that the IMCI has good sensitivity for correctly referring young infants and children requiring hospital admission in a developing country setting with a low prevalence of malaria . The guidelines ' moderate specificity will result in considerable over-referral of patients not needing admission , thereby decreasing opportunities for successful treatment of patients at first-level health facilities . The impact of the IMCI guidelines on children 's health and the health care system must be judged in the light of current treatment practice s , health outcomes and referral patterns Making a diagnosis is the bread and butter of clinical practice , but in light of the number of tests now available to clinician , diagnosing illness has become a complicated process . Guidelines for making an evidence -based diagnosis abound , but those making recommendations about diagnostic tests or test strategies must realize that clinicians require support to make diagnostic decisions that they can easily implement in daily practice . The Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) Working Group has developed a rigorous , transparent , and increasingly adopted approach for grading the quality of research evidence and strength of recommendations to guide clinical practice . This editorial summarizes GRADE 's process for developing recommendations for tests ( 1 ) . Clinicians are trained to use tests for screening and diagnosis ; identifying physiologic derangements ; establishing a prognosis ; and monitoring illness and treatment response by assessing signs and symptoms , imaging , biochemistry , pathology , and psychological testing techniques ( 2 ) . Sensitivity , specificity , positive predictive value , likelihood ratios , and diagnostic odds ratios are among the challenging terms that diagnostic studies typically deliver to clinicians , and all have to do with diagnostic accuracy . Not only do clinicians have difficulties remembering the definitions and calculations for these terms , application of the concepts to individual patients is often complicated . Many clinicians order a test despite uncertainty about how to interpret the result , and they also contribute to testing errors by incorrectly ordering tests ( 3 , 4 ) . GRADE 's framework for developing recommendations for diagnostic management studies is based on what is needed for practical clinical applicationthat is , how to weigh the benefits and harms of ordering and using a diagnostic test in caring for patients ( 1 ) . The approach begins with specifying the PICO : the relevant population ( P ) , diagnostic intervention or test ( I ) ( including its purpose , such as triage , replacement , or an add-on test ) , comparison test ( C ) , and patient-important outcomes ( O ) related to the use of a test for a focused clinical question . If a test fails to improve patient-important outcomes , there is no reason to use it , whatever its accuracy . For example , the results of genetic testing for Huntington chorea , an untreatable condition , may provide either welcome reassurance that a patient will not have the condition or the ability to plan for his future knowing that he will sadly fall victim ( 1 ) . Here , the ability to plan is analogous to an effective treatment , and the benefits of planning need to be balanced against the downsides of receiving an early diagnosis ( 5 - 7 ) . The best evidence of test performance comes from large r and omized trials of diagnostic strategies that directly measure patient-important outcomes ( 1 ) . However , these trials are few and far between : An informal review of the Cochrane data base of r and omized trials revealed < 100 such studies . Therefore , most recommendations about diagnostic testing are based on an implicit 2-step process of how the accuracy of a test indirectly changes patient-important outcomes . In the first step , a diagnostic-test accuracy study ( Figure ) , patients may receive both a new test and a reference test ( i.e. , the best available method for detecting the target condition ) . Investigators can then calculate the accuracy of the test compared with the reference test ( first step ) . In the second step , judgments about the patient importance of test accuracy are based on the consequences of being correctly or incorrectly classified as having or not having the disease . These include the benefits and harms of receiving treatment or follow-up tests for those correctly classified as having the disease , reassurance or receipt of other follow-up tests for those correctly classified as not having the disease , receipt of unnecessary treatment or additional tests for those incorrectly classified as having the disease , delayed or no treatment for those incorrectly classified as not having the disease , and any adverse effects of the diagnostic test ( e.g. , from invasive tests ) . Those making recommendations about diagnostic tests must then compare patient-important outcomes ( and costs ) in all patients receiving the new test with all patients receiving the old , or comparator , test . For the first step ( i.e. , assessing test accuracy ) , there are well-described method ological criteria for assessing risk for bias in an estimate of test accuracy , ideally based on a systematic review of relevant studies . For instance , studies of diagnostic test accuracy with a low risk for bias enroll consecutive patients for whom there is legitimate diagnostic uncertaintythat is , the type of patients to whom clinicians would apply the test in the course of regular clinical practice . If studies fail this criterion ( e.g. , only enroll patients with severe disease and healthy controls ) , the apparent accuracy of a test is likely to be misleadingly high ( 8 , 9 ) . The second step shown in the Figure is , in most situations , based on judgments of test accuracy as a surrogate for patient-important outcomes . The key issue about these judgments is that they should be made transparent to those using the recommendations . For example , in the diagnosis of suspected acute urolithiasis , well- design ed studies demonstrate fewer false-negative results with noncontrast helical computed tomography ( CT ) than with intravenous pyelography ( IVP ) ( 10 ) . However , those ureteric stones that CT detects but IVP misses are smaller and therefore are more likely to spontaneously pass . Before r and omized trials evaluating outcomes in patients treated for smaller stones , evidence from observational studies was of lower quality . Thus , it remained uncertain how patients were affected by missed cases and follow-up of incidental findings unrelated to renal calculi with CT . Recommendations about using one test ( IVP ) over the other ( helical CT ) were based on judgments of how the cases that were detected or missed would fare with or without treatment ( 11 ) . These judgments were likely to be based on indirect evidence and would be less certain than judgments based on direct evidence from a r and omized trial comparing the 2 tests . The GRADE approach requires making these judgments about the relation between accuracy and patient-important outcomes transparent . The example of IVP versus helical CT for patients with suspected acute shows exemplifies how the quality of evidence for an accurate test would be down grade d because of the lack of direct evidence on patient-important outcomes . Uncertainty about patient-important consequences and associated uncertainty about benefits and harms would probably have result ed in weak GRADE recommendations about the use of IVP compared with helical CT . Those making recommendations using the GRADE approach should also explicitly consider judgments and evidence about the values and preferences that patients attach to important consequences , as described more fully elsewhere ( 1 ) . Acknowledgments : This work was partially funded by a The human factor , mobility and Marie Curie Actions Scientist Reintegration European Commission Grant ( IGR 42192 ) GRADE to Dr. Schnemann |
702 | 17,909,138 | Cardiac arrhythmias and thrombocytopenia were more common with hypothermia ; however , they were clinical ly benign .
In neonates with postintrapartum asphyxial hypoxic-ischemic encephalopathy , hypothermia is effective in reducing death and moderate to severe neurodevelopmental disability either in combination or separately and is a safe intervention | null | null |
703 | 29,072,346 | The macroscopic design , the surface topography and the manipulation of the implant abutment did not have a significant influence on peri-implant inflammation .
In contrast , the abutment material demonstrated increased BOP values over time for Ti when compared to Zi abutments | OBJECTIVES The purpose of this systematic review was to evaluate the impact of the abutment characteristics on peri-implant tissue health and to identify the most suitable material and surface characteristics .
METHODS A protocol was developed aim ed to answer the following focused question : " Which is the effect of the modification of the abutment design in regard to the maintenance of the peri-implant soft tissue health ? " | The aim of this study of the present experiment was to study the marginal periimplant tissues at intentionally non-submerged ( 1-stage implants ) and initially submerged and subsequently exposed implants ( 2-stage implants ) . 5 beagle dogs , about 1-year-old , were used , 3 months after the extraction of the m and ibular premolars , fixtures of the Astra Tech Implants Dental System , the Brånemark System and the Bonefit -- ITI system were installed . In each m and ibular quadrant , 1 fixture of each implant system was installed in a r and omised order . The installation procedure followed the recommendations given in the manuals for each system . Thus , following installation , the bone crest coincided with the fixture margin of the Astra Tech Implants Dental System and the Brånemark System , whereas the border between the plasma sprayed and the machined surface of the Bonefit-ITI implant system was positioned at the level of the bone crest . Following a healing period of 3 months , abutment connection was carried out in the 2-stage systems ( the Astra Tech Implants Dental System and the Brånemark system ) . A 6-month period of plaque control was initiated . The animals were sacrificed and biopsies representing each important region dissected . The tissue sample s were prepared for light microscopy and exposed to histometric and morphometric measurements . The mucosal barrier which formed to the titanium surface following 1-stage and 2-stage implant installations comprised an epithelial and a connective tissue component , which for that 3 systems studied , had similar dimensions and composition . The amount of lamellar bone contained in the periimplant region close to the fixture part of the 3-implant systems was almost identical . It is suggested that correctly performed implant installation may ensure proper conditions for both and hard tissue healing , and that the geometry of the titanium implant seems to be of limited importance OBJECTIVES the aim of this r and omized-controlled clinical trial was to compare the objective and subjective esthetic outcomes of two types of screwed-retained single-implant crowns . MATERIAL S AND METHODS participants were r and omly assigned to the test ( all-ceramic ) and control [ porcelain-fused-to-ceramic ( PFM ) ] groups and were seen under investigation at baseline ( B ) , crown insertion ( CI ) , 1-year follow-up ( 1Y ) , and 2-year follow-up ( 2Y ) . Objective parameters were assessed by an intra-oral digital photograph ( 1:1 ratio ) , a study cast , a st and ardized radiograph , periodontal/peri-implant measurements , and question naires were obtained for the subjective parameters . In addition , pink esthetic score ( PES ) and white esthetic score ( WES ) were calculated for both groups . For the subjective evaluation , a visual analogue scale ( VAS ) question naire was used to assess the level of patient satisfaction regarding the esthetic outcome . Then , nine expert clinicians visually inspected and assessed subjective evaluation at the professional level . Statistical analysis was used to compare between groups and investigational appointments . RESULTS twenty patients were included in the study , 10 allocated to the all-ceramic group and 10 to the PFM group . No statistically significant differences were observed for the objective measurements comparing the test and control groups . Minor chipping of the ceramic veneering material was observed in the two patients of control group . The mean difference for all groups comparing objective parameters revealed an increase of papilla height between time points . A slight recession ( 0.26 mm ) of the peri-implant mucosal margin at the implant site was observed between 1Y and 2Y . Mean values for PES and WES were 13.9 and 13.1 for the PFM group and for the all-ceramic group , respectively . These values were not statistically significant . Implant crown volume , outline , translucency , and characterization showed major discrepancies with the contra-lateral natural teeth . As for subjective parameters , VAS patients ' responses regarding their perceptions of the esthetic outcome showed no statistical differences between groups and clinicians ' accuracy scores were 50 % and 47 % for PFM and all-ceramic crowns , respectively . CONCLUSION PFM and all-ceramic single-implant restorations may be indistinguishable from each other regarding the objective /subjective assessment of esthetic integration . The material chosen for fabricating an implant crown per se does not ensure an optimal esthetic outcome if other esthetic parameters are not present AIM This 1-year prospect i ve RCT compared the outcome of minimally ( turned ) and moderately rough ( TiUnite ) implant surfaces . MATERIAL AND METHODS Two subgroups of patients were formed ; one group ( n = 10 ) where all teeth had been extracted due to severe periodontitis , another group ( n = 8) with teeth in the antagonistic jaw with a history of periodontitis and some remaining medium pockets ( 4 - 6 mm ) . Implants ( n = 85 , 43 turned & 42 TiUnite ) were installed r and omly in each patient . After 3 - 6 months of submerged healing , healing abutments were connected , followed by final abutments 2 weeks later , all with the same surface characteristics as the supporting implant . Peri-implant parameters and intra-oral radiographs were recorded up to 1 year after abutment connection . RESULTS Two turned implants failed in the partial edentulous group during the initial healing period ( CSR : 95 % ) and none of the TiUnite ( CSR : 100 % ) surface . No statistically significant differences in clinical parameters could be observed between both surfaces . The partial edentulous subgroup showed more bone loss compared to the full edentulous subgroup . CONCLUSION Moderately rough implants have a similar clinical outcome ( at 1 year of loading in periodontitis susceptible patients ) compared to minimally rough implants Patients ’ esthetic expectations are increasing , and the options of the prosthetic pathways are currently evolving . The objective of this r and omized multicenter clinical trial was to assess and compare the esthetic outcome and clinical performance of anterior maxillary all-ceramic implant crowns ( ICs ) based either on prefabricated zirconia abutments veneered with pressed ceramics or on CAD/CAM zirconia abutments veneered with h and buildup technique . The null hypothesis was that there is no statistically significant difference between the 2 groups . Forty implants were inserted in sites 14 to 24 ( FDI ) in 40 patients in 2 centers , the Universities of Bern and Geneva , Switzerl and . After final impression , 20 patients were r and omized into group A , restored with a 1-piece screw-retained single crown made of a prefabricated zirconia abutment with pressed ceramic as the veneering material using the cut-back technique , or group B using an individualized CAD/CAM zirconia abutment ( CARES abutment ; Institut Straumann AG ) with a h and buildup technique . At baseline , 6 mo , and 1 y clinical , esthetic and radiographic parameters were assessed . Group A exhibited 1 dropout patient and 1 failure , result ing in a survival rate of 94.7 % after 1 y , in comparison to 100 % for group B. No other complications occurred . Clinical parameters presented stable and healthy peri-implant soft tissues . Overall , no or only minimal crestal bone changes were observed with a mean DIB ( distance from the implant shoulder to the first bone-to-implant contact ) of −0.15 mm ( group A ) and 0.12 mm ( group B ) at 1 y. There were no significant differences at baseline , 6 mo , and 1 y for DIB values between the 2 groups . Pink esthetic score ( PES ) and white esthetic score ( WES ) values at all 3 examinations indicated stability over time for both groups and pleasing esthetic outcomes . Both implant-supported prosthetic pathways represent a valuable treatment option for the restoration of single ICs in the anterior maxilla ( Clinical Trials.gov NCT02905838 ) OBJECTIVES To ( i ) investigate the influence of different extensions of a laser microgrooved abutment zone on connective tissue attachment and ( ii ) assess the impact of a repeated abutment dis-/reconnection on soft- and hard-tissue healing . MATERIAL S AND METHODS Titanium implants were inserted epicrestally in the lower jaws of six dogs . Healing abutments with either partially ( LP ) or completely ( LC ) laser microgrooved margins or machined surface margins ( M ) were r and omly allocated either to a single (1 × )/repeated ( 2 × ) dis-/reconnection at 4 and 6 weeks ( test ) , respectively , or left undisturbed ( control ) . At 6 and 8 weeks , histomorphometrical ( e.g. most coronal level of bone in contact with the implant [ CBI ] , subepithelial connective tissue attachment [ STC ] ) and immunohistochemical ( Collagen Type-I [ CI ] ) parameters were assessed . RESULTS At control sites , LP/LC groups revealed lower mean CBL ( 8 weeks , 0.95 ± 0.51 vs. 0.54 ± 0.63 vs. 1.66 ± 1.26 mm ) , higher mean STC ( 8 weeks , 82.58 ± 24.32 % vs. 96.37 ± 5.12 % vs. 54.17 ± 8.09 % ) , but comparable CI antigen reactivity . A repeated abutment manipulation was associated with increased mean CBL ( 8 weeks , 1.53 ± 1.09 vs. 0.94 ± 0.17 vs. 1.06 ± 0.34 mm ) , decreased STC ( 8 weeks , 57.34 ± 43.06 % vs. 13.26 ± 19.04 % vs. 37.76 ± 37.08 % ) and CI values . CONCLUSIONS It was concluded that ( i ) LC > LP abutments enhanced subepithelial connective tissue attachment and preserved crestal bone levels , ( ii ) repeated abutment dis-/reconnection during the initial healing phase ( 4 - 6 weeks ) may be associated with increased soft- and hard-tissue changes and ( iii ) LP and LC should be considered using a one abutment , one time approach OBJECTIVES To test the survival rates , and the technical and biological complication rates of customized zirconia and titanium abutments 5 years after crown insertion . MATERIAL AND METHODS Twenty-two patients with 40 single implants in maxillary and m and ibular canine and posterior regions were included . The implant sites were r and omly assigned to zirconia abutments supporting all-ceramic crowns or titanium abutments supporting metal-ceramic crowns . Clinical examinations were performed at baseline , and at 6 , 12 , 36 and 60 months of follow-up . The abutments and reconstructions were examined for technical and /or biological complications . Probing pocket depth ( PPD ) , plaque control record ( PCR ) and Bleeding on Probing ( BOP ) were assessed at abutments ( test ) and analogous contralateral teeth ( control ) . Radiographs of the implants revealed the bone level ( BL ) on mesial ( mBL ) and distal sides ( dBL ) . Data were statistically analyzed with nonparametric mixed models provided by Brunner and Langer and STATA ( P < 0.05 ) . RESULTS Eighteen patients with 18 zirconia and 10 titanium abutments were available at a mean follow-up of 5.6 years ( range 4.5 - 6.3 years ) . No abutment fracture or loss of a reconstruction occurred . Hence , the survival rate was 100 % for both . Survival of implants supporting zirconia abutments was 88.9 % and 90 % for implants supporting titanium abutments . Chipping of the veneering ceramic occurred at three metal-ceramic crowns supported by titanium abutments . No significant differences were found at the zirconia and titanium abutments for PPD ( meanPPDZrO2 3.3 ± 0.6 mm , mPPDTi 3.6 ± 1.1 mm ) , PCR ( mPCRZrO2 0.1 ± 0.3 , mPCRTi 0.3 ± 0.2 ) and BOP ( mBOPZrO2 0.5 ± 0.3 , mBOPTi 0.6 ± 0.3 ) . Moreover , the BL was similar at implants supporting zirconia and titanium abutments ( mBLZrO2 1.8 ± 0.5 , dBLZrO2 2.0 ± 0.8 ; mBLTi 2.0 ± 0.8 , dBLTi 1.9 ± 0.8 ) . CONCLUSIONS There were no statistically or clinical ly relevant differences between the 5-year survival rates , and the technical and biological complication rates of zirconia and titanium abutments in posterior regions PURPOSE This is a 2-year report from an ongoing prospect i ve 5-year multicenter study . The aim of the study was to evaluate the short- and long-term clinical function of CerAdapt ceramic abutments supporting short-span fixed partial dentures ( FPD ) . MATERIAL S AND METHODS Initially , 105 Brånemark System implants were placed in a total of 32 patients at 3 different clinics . After initial healing 103 implants remained . For the support of 36 FPDs , 53 ceramic and 50 titanium abutments were connected , 19 on ceramic and 17 on titanium abutments . RESULTS All patients remained in the study after 2 years . There was a cumulative survival rate of 97.1 % for implants and a cumulative success rate of 97.2 % for FPDs ( 94.7 % for ceramic and 100 % for titanium abutment-supported FPDs ) . One of 53 ceramic but none of 50 titanium abutments failed , giving a cumulative success rate of 98.1 % and 100 % , respectively , for the abutments . Soft tissue around abutments and adjacent teeth appeared healthy . More crown margins were placed submucosally at titanium ( 31 % ) than at ceramic ( 14 % ) abutments , and the level of the periimplant mucosa was relatively stable in relation to the abutment/crown . No differences were seen between ceramic and titanium abutments regarding bleeding of the periimplant mucosa . There was a minimal marginal bone loss recorded after 1 year , which was slightly more at titanium ( 0.4 mm ) than at ceramic ( 0.2 mm ) abutments . All patients and dentists were satisfied with the achieved esthetic result and no FPD was remade because of compromised esthetics . CONCLUSION So far the ceramic abutments have worked very well and the 2-year results have been very encouraging for CerAdapt abutments supporting short-span FPDs . However , ceramic material s tend to undergo static fatigue , and it is therefore important to wait for the 5-year results before making any more definite statement about the long-term prognosis for CerAdapt abutments PURPOSE The aim of the study was to evaluate the biological and technical outcomes of early and delayed placed single tooth implants after 10 years of follow-up . MATERIAL S AND METHODS Twenty consecutive patients who needed a single tooth replacement in the anterior maxilla were included in this study . Ten implants were placed with an early placement protocol , that is , 4 weeks after tooth extraction , whereas the other 10 implants were placed with a conventional delayed placement protocol , for example , 12 weeks after tooth extraction . At the baseline and at the annual re-examinations , pain from implant regions , mobility , plaque , mucositis , and marginal bone levels were recorded . Biological and technical complications were registered . The patients evaluated the functional and aesthetic outcomes subjectively on a visual analogue scale after 3 and 10 years . RESULTS All implants were still in situ after 10 years . The cumulative implant survival rate was 100 % . Two implant-supported crowns were remade because of ceramic fractures . The 10-year crown survival rate was 90 % . No significant differences in implant survival rates were found between the early and delayed protocol s , regarding plaque retention , mucositis , or marginal bone levels . After 10 years , the mean marginal bone loss at both sides of the implants was less than 1.0 mm in the two groups . During the 10-year interval , 1 patient lost more than 1.5 mm of marginal bone , 3 patients lost between 1.0 mm and 1.4 mm of bone , and 16 patients lost less than 1.0 mm of bone as an average of the mesial and distal bone loss . CONCLUSIONS This 10-year prospect i ve clinical trial demonstrated a 100 % implant survival and a 90 % crown survival . The average marginal bone level change was less than 1 mm , and there was no difference between early and delayed implant placement . Patient satisfaction with the implant-supported single crowns reduced with time INTRODUCTION Plasma application can lead to an improved adhesion between soft tissue and abutments and promotes cell spreading . OBJECTIVE A triple-blinded r and omized controlled clinical trial was performed to in vivo test the effect of cleaning abutment titanium surfaces with plasma of argon on cell adhesion and collagen fiber orientation at an early healing time . MATERIAL AND METHODS Thirty healthy patients with 30 submerged implants , at the second surgery , r and omly received either a specially design ed abutment with no additional treatment ( as they come from industry ; control group , G1 ) or cleaned by plasma of argon ( test group , G2 ) . Two weeks thereafter , a small biopsy including abutment and soft tissues around the abutment was performed . Abutments were analyzed using scanning electron microscopy to assess cell adhesion to the abutment surface . Outcome measures were the following : percentage of area occupied by cells , the presence or absence of cells , aspect of adhered cells , and the presence of contaminants . At the same time , the soft tissue histological analysis evaluated density and orientation of collagen fibers . Statistical analysis was performed using the Kolmogorov-Smirnov normality test and Levene variance homogeneity test . Data were analyzed using a nonparametric ranking test . The associations between the different qualitative variables were studied using Pearson 's chi-squared test . The Mann-Whitney U-test ( for two independent sample s ) was applied for quantitative variables . RESULTS Mean percentages of area occupied by cells were 15.14 % ( range 2.91 - 44.27 ) and 33.75 % ( range 2.37 - 68.4 ) for G1 and G2 , respectively . Differences were close to significance ( P = 0.089 ) . The proportion of sample s presenting adhered cells was homogeneous between the two groups ( P = 0.142 ) . In all cases , cells presented a flattened aspect , but not in three cases in the G2 ; in 17 cases , cells were efficiently adhered , and in 11 cases , cells presented filopodia with no statistical differences between groups ( P > 0.05 ) . No case from G2 showed contamination with cocobacteria with statistical differences between groups ( P = 0.006 ) . Collagen fiber density was higher in the basal , medial , and coronal area of G2 compared to G1 with a statistical difference in the internal area ( P < 0.05 ) . The orientation of the fibers varied according to the coordinate area with oblique fibers predominant in G2 than in G1 . CONCLUSION Plasma of argon may promote cell adhesion and positively influence collagen fiber orientation . A greater sample is necessary to confirm these preliminary results OBJECTIVES The aim was to test whether or not zirconia abutments exhibit the same survival and technical/biological outcome as titanium abutments . MATERIAL AND METHODS Twenty-two patients receiving 40 single-tooth implants in canine and posterior regions were included . The implant sites were r and omly assigned to 20 zirconia and 20 titanium abutments . All-ceramic and metal-ceramic crowns were fabricated . At baseline , 6 , 12 and 36 months , the reconstructions were examined for technical and biological problems . Probing pocket depth ( PPD ) , plaque control record ( PCR ) and bleeding on probing ( BOP ) were assessed at abutments ( test ) and analogous contralateral teeth ( control ) . St and ardized radiographs of the implants were made and the bone level ( BL ) was measured referring to the implant shoulder on mesial ( mBL ) and distal sides ( dBL ) . The difference of color ( DeltaE ) of the peri-implant mucosa and the gingiva of control teeth was assessed with a spectrophotometer . The data were statistically analyzed with Mann-Whitney Rank and Student 's unpaired t-tests . RESULTS Eighteen patients with 18 zirconia and 10 titanium abutments were examined at a mean follow-up of 36 months ( range 31.5 - 53.3 months ) . No fracture of an abutment or loss of a reconstruction was found . Hence , both exhibited 100 % survival . At two metal-ceramic crowns supported by titanium abutments chipping of the veneering ceramic occurred . No difference of the biological outcome of zirconia and titanium abutments was observed : PPD ( meanPPD(ZrO(2 ) ) 3.2 + /- 1 mm , mPPD(Ti ) 3.4 + /- 0.5 mm ) , PCR ( mPCR(ZrO(2 ) ) 0.1 + /- 0.2 , mPCR(Ti ) 0.1 + /- 0.2 ) and BOP ( mBOP(ZrO(2 ) ) 0.4 + /- 0.4 , mBOP(Ti ) 0.2 + /- 0.3 ) . Furthermore , the BL was similar at implants supporting zirconia and titanium abutments ( mBL(ZrO(2 ) ) 1.7 + /- 1 , dBL(ZrO(2 ) ) 1.6 + /- 1 ; mBL(Ti ) 2 + /- 1 , dBL(Ti ) 2.1 + /- 1 ) . Both , zirconia and titanium abutments induced a similar amount of discoloration of the mucosa compared with the gingiva at natural teeth ( DeltaE(ZrO(2 ) ) 9.3 + /- 3.8 , DeltaE(Ti ) 6.8 + /- 3.8 ) . CONCLUSIONS At 3 years , zirconia and titanium abutments exhibited same survival and technical , biological and esthetical outcomes PURPOSE A prospect i ve , r and omized , controlled 5-year multicenter study evaluated the long-term clinical function of CerAdapt ceramic abutments compared to titanium abutments on Brånemark implants supporting short-span fixed partial dentures ( FPD ) . MATERIAL S AND METHODS Initially , 105 Brånemark implants were placed in a total of 32 patients at three different clinics ; 103 implants remained after initial healing . Fifty-three ceramic and 50 titanium abutments were connected to support 36 FPDs , 19 on ceramic and 17 on titanium abutments . RESULTS Thirty patients with 29 FPDs were examined after 5 years . There was a cumulative success rate of 97.2 % for FPDs ( 94.7 % for ceramic and 100 % for titanium abutment-supported FPDs ) . One of 53 ceramic and none of 50 titanium abutments failed , giving survival rates of 98.1 % and 100 % , respectively . There was a mean marginal bone loss of 0.3 mm and 0.4 mm , respectively , for ceramic and titanium abutments . Soft tissues around abutments and adjacent teeth appeared healthy , and no significant differences were recorded for mucosal bleeding and plaque between ceramic and titanium abutments . Crown margins at FPD insertion were positioned as follows : 21 % submucosally , 33 % at the mucosal margin , and 46 % supramucosally . Changes in mucosal level were recorded at 12 % of the abutments , with 73 % of all changes recorded at ceramic abutments . There was a balance between more or less exposed crown margins during the first 2 years , in contrast to the 2- to 5-year period , when all changes meant less exposed margins . CONCLUSION Safe long-term functional and esthetic results can be achieved with CerAdapt alumina ceramic abutments on Brånemark implants for short-span FPDs AIM To compare the health of the soft tissues towards zirconia and titanium abutments in man , as observed using histological data . MATERIAL AND METHODS Twenty patients received two m and ibular implants with either a zirconia or titanium abutment ( split mouth study design , left-right r and omization ) . After 3 months soft tissue biopsies were prepared for histological evaluation . They were subjected to blind evaluation . The number of blood vessels per surface unit and an inflammation grading scale score ranging from 1 to 4 were determined . RESULTS Paired sample s from 17 patients were suitable for analysis , 3 with unsevered implant-abutment connections and 14 solely containing soft tissue . All showed a well-keratinized stratified squamous epithelium which was continuous with the barrier ( junctional ) epithelium that faced the abutment surface . The normal epithelial build-up could be recognized with little signs of inflammation . No statistically significant difference in tissues adjacent to zirconia and titanium abutment surfaces were seen with respect to vascular density ( 20.5 SD 4.4 and 20.7 SD 3.2 ) or inflammation grading scale scores ( 3.2 SD 0.7 versus 3.1 SD 0.7 ) . CONCLUSION No differences in soft tissue health were seen in peri-implant mucosa adjacent to zirconia and titanium abutment surfaces AIM This 3-year prospect i ve r and omized controlled trial compared the clinical , microbiological and biochemical outcome of minimally ( Turned , Tur ) and moderately rough ( TiUnite ( ® ) , TiU ) implant surfaces in a split-mouth design . MATERIAL AND METHODS The study population included 14 subjects : nine fully edentulous and five partially edentulous subjects with a history of periodontitis . Implants ( n = 78 , 39 Tur and 39 TiU ) were installed r and omly in each patient . Peri-implant clinical parameters and intra-oral radiographs were recorded after 3 years of loading . Subgingival plaque and peri-implant crevicular fluid sample s were collected and analysed using culture and quantitative polymerase chain reaction for the biofilm , and enzyme-linked immunosorbent assay for the concentration of osteoprotegerin and receptor activator of nuclear factor kappa-B lig and , respectively . RESULTS No statistically significant differences in clinical , microbiological and biochemical parameters could be observed when comparing the Tur and TiU implant surfaces . CONCLUSION After 3 years of loading , in periodontitis susceptible patients , the moderately rough , TiU implants demonstrated a similar clinical outcome compared with the smoother , turned implants . Longer follow-up and studies using different implant types are needed to confirm the statement that minimally and moderately rough implant surfaces perform similar , both from a clinical and from a microbiological point of view OBJECTIVES To investigate the impact of residual defect height ( RDH ) following guided bone regeneration ( GBR ) in dehiscence-type defects on the long-term stability of peri-implant health after a period of 4 years . MATERIAL AND METHODS The RDH values in dehiscence-type defects at titanium implants were clinical ly assessed after 4 months of submerged healing following augmentation using a natural bone mineral ( NBM ) and a r and omized application of either a cross-linked- ( VN ) or a native collagen membrane ( BG ) ( n=12 patients each ) . The RDH values were classified as absent ( 0 mm , control ; n=8 ) , minimal ( 1 mm , test 1 ; n=8 ) , or advanced ( > 1 mm , test 2 ; n=8 ) . Clinical parameters ( i.e. bleeding on probing [ BOP ] , probing pocket depth [ PD ] , mucosal recession [ MR ] ) were recorded ( mesio- , mid- , and disto-buccal aspects ) at 4 years after prosthesis installation . RESULTS The mean PD ( 2.9±0.7 , 2.8±0.7 , 2.7±0.8 mm ) values at 4 years were comparable in all the groups investigated . The mean MR values tended to be increased in both the test groups ( 0.5±0.7 , 0.4±0.6 mm , respectively ) , when compared with the control group ( 0.2±0.3 mm ) ( P>0.05 , respectively ) . The mean BOP values were also increased in both the test groups ( 45.8±30.5 % , 54.1±24.8 % , respectively ) , even reaching statistical significance when comparing test 2 and control ( 29.1±21.3 % ) groups ( P=0.02 ) . CONCLUSION The present study indicated that ( i ) implants exhibiting RDH values > 1 mm are at a higher risk of developing peri-implant disease and ( ii ) positive RDH values may be associated with an increase in MR and may therefore compromise the overall esthetic outcome of implant therapy AIM To assess and characterize pollution micro-particles and bacterial growth on customized titanium abutments after steaming , ultrasonic and plasma cleaning treatments . MATERIAL S AND METHODS Thirty commercially available implant abutments , after customization , were r and omly divided into 3 groups of 10 and cleansed by steam ( considered as control group ) , ultrasonic cleaning ( test group 1 ) and plasma of Argon ( test group 2 ) . For all specimens , SEM analysis and EDAX micro analysis were performed to count and characterize pollution micro-particles , both on the abutment surface and implant-abutment connection . For the control and test groups , mean values and st and ard deviations were calculated for number and density of micro-particles . Statistical differences were determined by one-way ANOVA with Scheffe multiple comparison test . The level of statistical significance was set at P ≤ 0.05 . Additional microbiologic analysis was performed to detect bacterial contamination on the abutment surface . RESULTS In the control group , the number of micro-particles on average was 117.5 , and 14.1 , respectively , on the abutment surface and connection . In the test groups , no pollution was revealed on the abutment ( average of 1.09 and 1.13 spots , respectively , in test group 1 and test group 2 ) and connection ( 1.28 and 1.41 , respectively , in test group 1 and test group 2 ) . The analysis of variance ( ANOVA ) showed a statistically significant difference for all the variables examined . For each variable , at least one of the groups differs from the others . Scheffe multiple comparison test showed that all comparisons for every variables between the control group and both groups are significant , while there were some comparisons between test group 1 and test group 2 that were not significant . EDAX micro analysis identified micro-particles as residual of lubricant mixed with traces of Titanium and other metals . Microbiologic analysis demonstrated the presence of bacterial growth on the abutment surface only in the control group ( 111.5 ± 11.43 CFU/ml/implant-abutment as mean value ) . In the test groups , absence of growing microorganisms was found . CONCLUSIONS This study confirmed that both plasma and ultrasonic treatments can be beneficially adopted for abutment cleaning process after laboratory technical stages , to supposedly favor soft tissue healing and implant-prosthetic connection stability OBJECTIVES To histologically evaluate and compare the performance of healing abutments with either hydrophobic or hydrophilic surface properties in humans . MATERIAL S AND METHODS According to a parallel-group design , titanium implants placed in the posterior m and ible and maxilla of 30 patients were r and omly assigned to either ( 1 ) hydrophobic machined ( M ) , ( 2 ) chemically modified hydrophilic ( mod ) acid etched ( MA ) titanium ( Ti ) ( modMA1 ) or ( 3 ) modMA Ti- Zirconium alloy ( modMA2 ) healing abutments and left to heal in a transmucosal position . At 8 weeks , the abutments and a limited soft tissue biopsy were harvested according to a st and ardized procedure and processed for histological analysis ( primary outcomes : percentage epithelial- ( EC ) and subepithelial connective tissue contact ( CTC ) to the abutment surface ) . RESULTS The surgical procedure was associated with an incomplete mucosal coverage of the study abutments in nine patients , and an unintentional submerged healing procedure in three patients . Per protocol analysis ( 18 patients ) has pointed to an improved quantitative EC [ modMA2 ( 53.45 ± 28.25 ) > modMA1 ( 32.25 ± 24.3 ) > M ( 23.15 ± 16.09 ) ] and CTC [ modMA2 ( 75.12 ± 43.22 ) > modMA1 ( 69.41 ± 46.74 ) > M ( 47.63 ± 19.28 ) ] ( % ) to modMA surfaced abutments . CONCLUSIONS It was concluded that modMA surfaces may have the potential to enhance soft tissue adhesion at the transmucosal aspect of titanium dental implants BACKGROUND While information on the prevalence of peri-implantitis is available , data describing onset and progression of the disease are limited . MATERIAL & METHODS A 9-year follow-up examination of 596 r and omly selected implant-carrying individuals identified 62 patients with moderate/severe peri-implantitis . Longitudinal assessment s of peri-implant marginal bone levels were used to construct a statistical model with bone loss as the dependent variable . A multilevel growth model estimated the pattern of bone loss for each implant/patient . Onset of peri-implantitis was determined by evaluating the cumulative percentage of implants/ patients presenting with estimated bone loss at each year following prosthesis delivery . RESULTS The analysis showed a non-linear , accelerating pattern of bone loss at the 105 affected implants . The onset of peri-implantitis occurred early , and 52 % and 66 % of implants presented with bone loss of > 0.5 mm at years 2 and 3 respectively . A total of 70 % and 81 % of subjects presented with ≥1 implants with bone loss of > 0.5 mm at years 2 and 3 respectively . CONCLUSIONS It is suggested that peri-implantitis progresses in a non-linear , accelerating pattern and that , for the majority of cases , the onset occurs within 3 years of function OBJECTIVES To assess the bleeding on probing ( BOP ) tendency and periodontal probe penetration when applying various probing forces at implant sites in patients with a high st and ard of oral hygiene with well-maintained peri-implant tissues . MATERIAL AND METHODS Seventeen healthy patients with excellent oral hygiene in a maintenance program after having been treated for periodontitis or gingivitis were recruited . Missing teeth had been replaced using oral implants . The BOP and probing depth ( PPD ) were assessed at the mid-buccal , mid-oral , mesial and distal aspects of the buccal surfaces of each implant . Moreover , contralateral teeth were design ated and assessed for BOP and PPD in the same locations and at the same observation visits . At each visit , implants and contralateral teeth were r and omly assigned to one of the st and ardized probing forces ( 0.15 or 0.25 N ) . The second probing force was applied at the repetition of the examination 7 days later . RESULTS Increasing the probing pressure by 0.1 N from 0.15 N result ed in an increase of BOP percentage by 13.7 % and 6.6 % for implants and contralateral teeth , respectively . There appeared to be a significant difference of the mean BOP percentage at implant and tooth sites when a probing pressure of 0.25 N was applied . A significantly deeper mean PPD at implant sites compared with tooth sites was found irrespective of the probing pressure applied . CONCLUSIONS The results of the present study demonstrated that 0.15 N might represent the threshold pressure to be applied to avoid false positive BOP readings around oral implants . Hence , probing around implants demonstrated a higher sensitivity compared with probing around teeth BACKGROUND Contamination of implant abutments could potentially influence the peri-implant tissue inflammatory response . The aim of the present study is to assess the radiographic bone changes around customized , platform-switched abutments placed according to the " one-abutment-one-time " protocol , with and without plasma of argon cleaning treatment . METHODS Thirty healthy patients with thin gingival biotype ( < 1 mm ) and history of periodontal disease received one maxillary implant each . Immediately before abutment connection , patients were r and omly assigned to control group ( cleaning protocol by steaming ) or test group ( plasma of argon treatment ) . Outcome measures were : 1 ) success rate of implants and prostheses ; 2 ) biologic and prosthetic complications ; 3 ) peri-implant marginal bone loss ( MBL ) ; 4 ) esthetic and periodontal parameters ; and 5 ) patient satisfaction . RESULTS Neither implants nor prostheses were lost in either group at the 5-year follow-up examination . Overall , both groups showed a slight amount of peri-implant bone loss from baseline to 5 years . A statistically higher mean MBL was found in the control group compared with the test group at 6 , 24 , and 60 months after crown connection . Nevertheless , during the entire follow-up period , intragroup comparison demonstrated statistically significant mean MBL in the control group , but not in the test group . The test group showed a higher mean gain at the soft tissue margin , but not for the papilla . All implants showed good periodontal parameters , with no significant differences between groups . CONCLUSION Plasma of argon could be used to disinfect implant abutments before insertion to minimize future peri-implant bone resorption BACKGROUND The aim of the present study in humans was to conduct a comparative immunohistochemical evaluation of vascular endothelial growth factor ( VEGF ) and nitric oxide synthase ( NOS ) expression , inflammatory infiltrate , proliferative activity expression , and microvessel density ( MVD ) in peri-implant soft tissues of titanium and zirconium oxide healing caps . METHODS Five patients , three men and two women ( aged 30 to 66 years ; mean : 49 years ) , participated in this study . All patients received dental implants that were 3.8 mm in diameter and 11 mm in length . All implants were left to heal in a non-submerged ( single-stage ) mode . Healing caps ( 3.8 mm in diameter and 3.0 mm in height ) were inserted in all implants . Half of the implants were supplied with st and ard , prefabricated caps of commercially pure titanium , whereas the other half were provided with test zirconium oxide caps . After a 6-month healing period , a gingival biopsy was performed with a circular scalpel ( 5.5 mm in diameter ) around the healing caps of both groups , without unscrewing or removing the healing caps . The dimensions of the gingival biopsies were 1.7 mm ( 5.5 - 3.8 mm ) in thickness and 3 mm in height . RESULTS Statistically significant differences were found in the microvessel density between titanium and zirconium oxide healing caps and group II ( P < or = 0.0001 ) . Statistically significant differences were likewise found in the low and high intensities of NOS1 , NOS3 , and VEGF ( P < or = 0.0001 ) . In conclusion , the high intensity of NOS1 , NOS3 , and VEGF were mostly expressed in the titanium group , whereas the low intensity of NOS1 , NOS3 , and VEGF were mostly expressed in the zirconium oxide group . CONCLUSIONS In our specimens , the inflammatory infiltrate was mostly present in the titanium specimens . Their extension was much larger than that of the zirconium oxide specimens . Higher values of MVD were observed in the titanium specimens ( 29.1 versus 15.8 ) . In addition , a higher expression of VEGF intensity was observed in the peri-implant tissues of titanium healing caps , whereas predominantly lower expressions of VEGF intensity were noted around the zirconium oxide healing caps . The Ki-67 expression was higher in the titanium specimens . All these data revealed that the tissues around titanium healing caps underwent a higher rate of inflammation-associated processes , most probably correlated to the higher inflammation processes observed in these tissues . A higher intensity expression of NOS1 and NOS3 was recorded in the tissues around titanium , whereas , on the contrary , a lower intensity of expression was found in the tissues around zirconium oxide specimens . These latter data indicate that the higher expression of these two mediators could be correlated to the higher amount of bacteria present around the titanium sample AIM To evaluate the aesthetic outcomes of zirconia versus titanium abutments for single tooth implant-supported crowns in the anterior maxilla . MATERIAL & METHODS A parallel , double blind clinical trial was conducted at the Complutense University ( Madrid ) , where 38 patients were recruited . After r and om allocation ( via computer-generated permuted blocks ) , either zirconia ( test ) or titanium ( control ) abutments were placed . Intra- and inter-group differences in aesthetic ( main outcome ) , clinical , radiographical , and patient-centred outcomes were evaluated at baseline ( crown placement ) and at 1-year follow-up . RESULTS At 1 year , 25 of the 30 r and omized patients were analysed ( 11 test and 14 control ) . Using the Implant Crown Aesthetic Index ( ICAI ) , the scoring at baseline and 1-year were 7.9 and 7.6 for the test group and 10.6 and 11.3 for the control group , respectively . These differences were not statistically significant ( sample size non-contrasted ) . Patient satisfaction was similarly high in both groups ( visual analogue scale 8.5 ) . Furthermore , no differences were observed in the clinical or radiographical outcomes . Two abutment fractures were registered in the test group . CONCLUSIONS The use of zirconia abutments demonstrated a tendency towards better aesthetic outcomes although the differences were not statistically significant . However , more technical complications were noted with the use of zirconia abutments AIM The aim of this prospect i ve cohort study was to evaluate clinical , radiographic , technical , esthetic , and patient-centered outcomes of implants using two different restoration material s after 5 - 9 years . MATERIAL S AND METHODS The study included 28 patients ( test group : 13 patients with all-ceramic crowns on aluminum oxide-based abutments ; control group : 15 patients with metal abutments on porcelain-fused-to-metal crowns ) . Evaluation of patient satisfaction , clinical ( periodontal probing depth , bleeding on probing , plaque index , mucosal recession , and width of keratinized mucosa ) , esthetical ( papilla index , clinical crown length ) , technical ( loss of retention , marginal adaptation , chipping of ceramic , anatomical shape , occlusal wear , color match ) , and radiological parameters were assessed . The statistical analyses included comparison of all-ceramic vs. metal abutments and between the groups using Mann-Whitney U-tests . For esthetic parameters , changes over time were assessed using Friedman test and post hoc Wilcoxon test of all complete cases . RESULTS The survival rate of the restoration was 100 % in both groups . Patient 's satisfaction revealed 9.7 on the visual analog scale . A low satisfaction correlated with low ratings in color or anatomical shape . The mucosal recession in the test group was less than that in the control group . An increase in distal papilla height in the year 0 to 1 , and a decrease from year 1 to 8 , was detected . Sites , which received a soft tissue graft , revealed stable papillae over the observation period . Clinical crown length showed higher values in the control group . CONCLUSIONS Within the limitations of the study , it can be concluded that all-ceramic restorations reveal a high survival rate of 100 % and show no difference to metal after a mean observation period of 7.2 years OBJECTIVE The aim of the present study was to analyze the soft tissue barrier formed to implant abutments made of different material s. MATERIAL AND METHODS Six Labrador dogs , about 1 year old , were used . All m and ibular premolars and the first , second and third maxillary premolars were extracted . Three months later four implants ( OsseoSpeed , 4.5 x 9 mm , Astra Tech Dental , Mölndal , Sweden ) were placed in the edentulous premolar region on one side of the m and ible and healing abutments were connected . One month later , the healing abutments were disconnected and four new abutments were placed in a r and omized order . Two of the abutments were made of titanium ( Ti ) , while the remaining abutments were made of ZrO(2 ) or AuPt-alloy . A 5-months plaque control program was initiated . Three months after implant surgery , the implant installation procedure and the subsequent abutment shift were repeated in the contra-lateral m and ibular region . Two months later , the dogs were euthanized and biopsies containing the implant and the surrounding soft and hard peri-implant tissues were collected and prepared for histological analysis . RESULTS It was demonstrated that the soft tissue dimensions at Ti- and ZrO(2 ) abutments remained stable between 2 and 5 months of healing . At Au/Pt-alloy abutment sites , however , an apical shift of the barrier epithelium and the marginal bone occurred between 2 and 5 months of healing . In addition , the 80-mum-wide connective tissue zone lateral to the Au/Pt-alloy abutments contained lower amounts of collagen and fibroblasts and larger fractions of leukocytes than the corresponding connective tissue zone of abutments made of Ti and ZrO(2 ) . CONCLUSION It is suggested that the soft tissue healing to abutments made of titanium and ZrO(2 ) is different to that at abutments made of AuPt-alloy BACKGROUND It has been shown that peri-implant crestal bone reactions are influenced by both a rough-smooth implant border in one-piece , non-submerged , as well as an interface ( microgap [ MG ] between implant/abutment ) in two-piece butt-joint , submerged and non-submerged implants being placed at different levels in relation to the crest of the bone . According to st and ard surgical procedures , the rough-smooth implant border for implants with a smooth collar should be aligned with the crest of the bone exhibiting a smooth collar adjacent to peri-implant soft tissues . No data , however , are available for implants exhibiting a s and blasted , large-grit and acid-etched ( SLA ) surface all the way to the top of a non-submerged implant . Thus , the purpose of this study is to histometrically examine crestal bone changes around machined versus SLA-surfaced implant collars in a side-by-side comparison . METHODS A total of 60 titanium implants ( 30 machined collars and 30 SLA collars ) were r and omly placed in edentulous m and ibular areas of five foxhounds forming six different subgroups ( implant subgroups A to F ) . The implants in subgroups A to C had a machined collar ( control ) , whereas the implants in subgroups D to F were SLA-treated all the way to the top ( MG level ; test ) . Furthermore , the MGs of the implants were placed at different levels in relation to the crest of the bone : the implants in subgroups A and E were 2 mm above the crest , in subgroups C and D 1 mm above , in subgroup B 3 mm above , and in subgroup F at the bone crest level . For all implants , abutment healing screws were connected the day of surgery . These caps were loosened and immediately retightened monthly . At 6 months , animals were sacrificed and non-decalcified histology was analyzed by evaluating peri-implant crestal bone levels . RESULTS For implants in subgroup A , the estimated mean crestal bone loss ( ± SD ) was -0.52 ± 0.40 mm ; in subgroup B , + 0.16 ± 0.40 mm ( bone gain ) ; in subgroup C , -1.28 ± 0.21 mm ; in subgroup D , -0.43 ± 0.43 mm ; in subgroup E , -0.03 ± 0.48 mm ; and in subgroup F , -1.11 ± 0.27 mm . Mean bone loss for subgroup A was significantly greater than for subgroup E ( P = 0.034 ) and bone loss for subgroup C was significantly greater than for subgroup D ( P < 0.001 ) . CONCLUSIONS Choosing a completely SLA-surfaced non-submerged implant can reduce the amount of peri-implant crestal bone loss and reduce the distance from the MG to the first bone-implant contact around unloaded implants compared to implants with a machined collar . Furthermore , a slightly exposed SLA surface during implant placement does not seem to compromise the overall hard and soft tissue integration and , in some cases , results in coronal bone formation in this canine model PURPOSE The purpose of this study was to investigate the early tissue response around three one-piece implant systems with different transmucosal design s. MATERIAL S AND METHODS Three one-piece dental implant systems with different profiles and surface roughnesses on the transmucosal portion were examined in the current study . The transmucosal portions were flared and machined ( FM ) , concave and machined with microgrooves ( CMG ) , or straight and anodic oxidized ( SA ) . A total of 30 implants ( 10 of each type ) were placed in computer-generated r and omized order in the m and ibular residual ridges of five beagle dogs . Six months later , all animals were sacrificed and histologic sections were prepared to measure epithelial tissue height , connective tissue contact , and the amount of bone resorption . One-way analysis of variance and the Bonferroni post hoc test were used for statistical evaluation ( alpha = 95 % ) . RESULTS After a 6-month nonfunctional loading period , all 30 implants were clinical ly immobile . Slight swelling and redness of the peri-implant soft tissue were noticed around most of the implant abutments . Histometric analysis showed that the FM implants had a longer epithelial tissue height than the CMG implants . The CMG implants showed the greatest amount of connective tissue attachment among the three groups and the least amount of marginal bone resorption . The CMG and SA implants showed bone growth above the initial reference point at 10 and 7 measurement sites , respectively , whereas no bone overgrowth was noted around the FM implants . CONCLUSION Based on this study conducted in five beagle dogs , a concave transmucosal profile with a microgrooved surface was associated with longer connective tissue attachments and less bone resorption versus implants that were flared with a machined surface or straight with an anodic oxidized surface in the early healing phase . Int J Oral Maxillofac Implants 2010;25:309 - 314 BACKGROUND A lack of evidence is present in literature regarding the clinical relevance of micropollution and bacterial contamination present on customized titanium abutments following laboratory stages and steaming cleaning procedures . To preserve abutments from such pollutants , plasma of argon cleaning of customized abutments was advocated . AIM The aim of this prospect i ve , r and omized , match-paired , triple-blinded , controlled , clinical trial is to longitudinally assess radiographical marginal bone-level changes around implants restored according to the platform switching and " one-abutment-one-time " concepts , using commercially available abutments , with and without plasma of argon cleaning treatment after customization . MATERIAL S AND METHODS Thirty patients with thin gingival biotype , a history of periodontal disease , and in general good health received one implant in the anterior maxilla or premolar region . Patients were r and omly assigned to control ( abutment subjected only to usually adopted cleaning protocol by steam ) and test group ( abutment subjected to plasma of argon treatment ) . Periapical st and ardized digital radiographs were taken at the time of crown connection ( T0 ) , 6 ( T1 ) and 24 months after the final restoration ( T2 ) . Average mesial-distal bone-level changes mean values with st and ard deviations ( SD ) were calculated . The Mann-Whitney U-test was selected to identify differences in bone-level changes between test and control groups . RESULTS An average interproximal bone loss of 0.16 mm ( SD : 0.17 ) and 0.07 mm ( SD : 0.34 ) was revealed in the control and test group at 6 months ( T1 ) , respectively , while after 24 months , groups showed a mean bone-level changes of 0.38 mm ( SD : 0.44 ) and 0.11 mm ( SD : 0.14 ) , respectively . Statistically significant differences among control and test groups were found at both time points . Intergroup comparison relived absence of statistically significant difference . CONCLUSION Plasma-cleaning treatment of implant titanium abutments , together with platform switching and one-abutment-one-time concepts , could be favorable in terms of hard-tissue-level changes , also in critical conditions such as in patients with a history of periodontal disease , presenting thin gingival biotype PURPOSE To assess the response of soft tissues around two different abutment design s in healed sites in the esthetic zone . MATERIAL S AND METHODS Twenty-six subjects received two endosseous implants in healed , bilateral implant sites in the esthetic zone in the maxilla or the m and ible . After 17 to 19 weeks and left/right r and omization , the implants were restored with either a conventional ( control ) or curved ( experimental ) titanium abutment and a provisional crown . Eight weeks after abutment placement , definitive crowns were cemented ( T0 ) . Soft tissue development was assessed based on peri-implant bone loss , Pink Esthetic Score ( PES ) , and probing depths immediately after placement of the definitive crown and after 1 year ( T12 ) and compared between sites . Possible confounding variables ( abutment angle , plaque presence , gingival bleeding , width of attached mucosa ) were also documented at T0 and T12 . RESULTS The mean peri-implant marginal bone loss from T0 to T12 was 0.00 ± 0.37 mm in the experimental group and 0.12 ± 0.27 mm in the control group . Differences were not statistically significant ( P = .25 ) . At T12 , the curved abutment scored a mean PES of 10 ± 2.3 and the straight abutment scored 9.7 ± 2.3 . The difference was not significant ( P = .46 ) ) . Probing depths were also not significantly different between the two groups ( P = .85 ) . Correlation and regression analysis showed no hints of predictive behavior for the possible confounding variables . CONCLUSION A titanium abutment with a circumferential curved design is of no additional benefit to soft tissue development and preservation of marginal bone compared to a conventional straight abutment design for the restoration of single-tooth implants in the esthetic zone PURPOSE The aim of the study was to compare results after 1 and 3 years when single crowns supported by CerAdapt ( test ) ceramic abutments or CeraOne ( control ) titanium abutments were loaded . MATERIAL S AND METHODS The material was divided into two groups : in group A , 69 ( 34 test , 35 control ) abutments/crowns from all involved clinics were followed for 1 year ; and in group B , 20 ( 10 test , 10 control ) abutments/crowns from one of the clinics were followed for 3 years . RESULTS No implant failed , giving a cumulative success rate of 100 % for the implants . Two CerAdapt abutments in group A fractured , giving a cumulative success rate of 93 % for the CerAdapt and 100 % for the CeraOne abutments after 1 year . No abutment failed in group B , giving a cumulative success rate of 100 % both for the CerAdapt and the CeraOne abutments between 1 and 3 years . The CerAdapt fractures might have been due to the fact that the abutments were impaired through too-extensive preparation and /or had been exposed to a too-high bending moment . Almost no marginal bone loss was recorded , indicating a stable bone situation both at CerAdapt and CeraOne abutments on single-tooth implants . Healthy conditions , with a relatively stable level of the periimplant mucosa in relation to the abutment/crown , were recorded for soft tissues both at CerAdapt and CeraOne abutments . Both clinicians and patients rated the esthetic result as excellent for practically all cases . CONCLUSION The results demonstrate the esthetic possibilities and the safety of single-tooth replacement when accepted treatment concepts are followed and documented components are used . The tested abutments worked well , although the fractured CerAdapt abutments indicate that ceramic abutments are more sensitive to h and ling procedures than the titanium abutments BACKGROUND Following connection to the oral cavity , osseointegrated dental implants and surrounding tissues are exposed to microbiologic and biomechanical challenges . The establishment of a firm functional periimplant soft tissue barrier ( PSTB ) is considered to be important to protect the implant 's interface from invasion of bacteria . The current knowledge on the histologic architecture of the PSTB is mainly based on animal experiments . PURPOSE The aim of this study was to histologically characterize the PSTB formed in humans around experimental one-piece mini-implants with different surface topography . MATERIAL S AND METHODS Five patients received a total of 12 experimental titanium , one-piece mini-implants with an oxidized ( n = 4 ) , an acid-etched ( n = 4 ) , or a machined ( n = 4 ) surface distal to therapeutic implants . Following transmucosal healing of 8 weeks and at abutment connection of the regular implants , the mini-implants were harvested with a layer of surrounding hard and soft tissue . The specimens were fixed and processed for histologic sectioning according to st and ard procedures . The most central bucco-oral section cut in the long axis was used for morphologic analyses of the PSTB . The vertical soft tissue morphology was quantified using histometric measurements . RESULTS The overall height of the soft tissue , that is , the biologic width , was around 4 to 4.5 mm and consisted of an epithelial and a supracrestal connective tissue barrier . The junctional epithelium established the attachment to the implant surface , whereas the collagen fibers and fibroblasts of the connective tissue seal were oriented parallel to the implant . The epithelial attachment was shorter at the oxidized and acid-etched surfaces compared with the machined surfaces . Accordingly , the oxidized and acid-etched mini-implants exhibited a longer zone of connective tissue seal . CONCLUSION The periimplant soft tissue formed at the experimental one-piece mini-implants in humans was of a character similar to that described in animal studies . The oxidized and acid-etched implants revealed less epithelial downgrowth and longer connective tissue seal than machined implants OBJECTIVES The aim of this study was to test whether or not customized zirconia abutments exhibit the same survival rates in canine and posterior regions as titanium abutments , and to compare the esthetic result of the two abutment types . MATERIAL AND METHODS Twenty-two patients with 40 implants in posterior regions were included and the implant sites were r and omly assigned to 20 customized zirconia and 20 customized titanium abutments . All-ceramic ( AC ) and metal-ceramic ( MC ) crowns were fabricated . In all except two cases , the crowns were cemented on the abutments using resin or glass-ionomer cements . Two zirconia reconstructions were screw retained . At baseline , 6 and 12 months , the reconstructions were examined for technical and biological problems . Probing pocket depth ( PPD ) , plaque ( Pl ) and bleeding on probing ( BOP ) were assessed and compared with natural control teeth . Furthermore , the difference of color ( DeltaE ) of the peri-implant mucosa and the gingiva of control teeth was evaluated by means of a spectrophotometer ( Spectroshade ) . The data were analyzed with Student 's unpaired t-test , ANOVA and regression analyses . RESULTS Twenty patients with 19 zirconia and 12 titanium abutments were examined at a mean follow-up of 12.6+/-2.7 months . The survival rate for reconstructions and abutments was 100 % . No technical or biological problems were found at the test and control sites . Two chippings ( 16.7 % ) occurred at crowns supported by titanium abutments . No difference was found regarding PPD ( meanPPD(ZrO2 ) 3.4+/-0.7 mm , mPPD(Ti ) 3.3+/-0.6 mm ) , Pl ( mPl(ZrO2 ) 0.2+/-0.3 , mPl(Ti ) 0.1+/-1.8 ) and BOP ( mBOP(ZrO2 ) 60+/-30 % , mBOP(Ti ) 30+/-40 % ) between the two groups . Both crowns on zirconia and titanium abutments induced a similar amount of discoloration of the soft tissue compared with the gingiva at natural teeth ( DeltaE(ZrO2 ) 8.1+/-3.9 , DeltaE(Ti ) 7.8+/-4.3 ) . CONCLUSIONS At 1 year , zirconia abutments exhibited the same survival and a similar esthetic outcome as titanium abutments OBJECTIVE To compare the peri-implant soft tissue dimensions after insertion of single-implant crowns in the anterior maxilla . MATERIAL S AND METHODS Twenty patients were accepted according to well-defined inclusion criteria and r and omized to porcelain-fused-to-metal ( PFM ) or all-ceramic groups . Follow-up was at : Baseline ( B ) , Crown Insertion ( CI ) , 1-year ( 1Y ) , and 2-year ( 2Y ) . The following parameters were statistically analysed : distance implant shoulder to marginal peri-implant mucosa ( DIM ) , papilla height ( PH ) , width of keratinized mucosa ( KM ) , crestal bone level ( CBL ) , full mouth plaque score ( FMPS ) , full mouth bleeding score ( FMBS ) , and probing pocket depth . RESULTS Between groups measurements for DIM , PH , KM , CBL , FMPS , and FMBS showed no statistically significant differences except the distal CBLs to adjacent tooth . DIM ( mid-facial ) decreased from B to CI remaining stable at 1Y and 2Y ( p-value 0.0014 ) . DIM mesial and distal aspects significantly increased from B to CI showing signs of stability at the 2Y . PH between B and CI increased at the mesial site and at the distal site , thereafter , peri-implant soft tissues were stable at the 2Y . CONCLUSION The insertion of an implant crown affects the peri-implant mucosa morphology by an apical displacement at the mid-facial aspect and coronal at mesial and distal sites |
704 | 23,612,781 | To conclude , there is limited evidence to support the prescription of LWI to people with medial compartment osteoarthritis to reduce pain and increase function .
However , there remains a paucity of evidence to determine whether LWI outcomes differ in subgroups of the patients , such as severe compared to mild osteoarthritis , obese patients , or whether the angle of LWI is of clinical importance | A conservative management strategy for knee osteoarthritis is the lateral wedge insole ( LWI ) .
The theoretical basis for this intervention is to correct tibiofemoral malalignment , thereby reducing pain and optimising function .
This systematic review evaluates the evidence on the effectiveness and safety of LWI for the treatment for knee osteoarthritis . | Background There is controversial evidence regarding whether foot orthoses or knee braces improve pain and function or correct malalignment in selected patients with osteoarthritis ( OA ) of the medial knee compartment . However , insoles are safe and less costly than knee bracing if they relieve pain or improve function . Questions / purpose sWe therefore asked whether laterally wedged insoles or valgus braces would reduce pain , enhance functional scores , and correct varus malalignment comparable to knee braces . Patients and Methods We prospect ively enrolled 91 patients with symptomatic medial compartmental knee OA and r and omized to treatment with either a 10-mm laterally wedged insole ( index group , n = 45 ) or a valgus brace ( control group , n = 46 ) . All patients were assessed at 6 months . The primary outcome measure was pain severity as measured on a visual analog scale . Secondary outcome measures were knee function score using WOMAC and correction of varus alignment on AP whole-leg radiographs taken with the patient in the st and ing position . Additionally , we compared the percentage of responders according to the OMERACT-OARSI criteria for both groups . Results We observed no differences in pain or WOMAC scores between the two groups . Neither device achieved correction of knee varus malalignment in the frontal plane . According to the OMERACT-OARSI criteria , 17 % of our patients responded to the allocated intervention . Patients in the insole group complied better with their intervention . Although subgroup analysis results should be translated into practice cautiously , we observed a slightly higher percentage of responders for the insole compared with bracing for patients with mild medial OA . Conclusions Our data suggest a laterally wedged insole may be an alternative to valgus bracing for noninvasively treating symptoms of medial knee OA.Level of Evidence Level I , therapeutic study . See the Guidelines for Authors for a complete description of level of evidence We examined if a subject-specific amount of lateral wedge added to a foot orthosis could alter knee mechanics to potentially reduce the progression of knee osteoarthritis in patients with medial knee osteoarthritis . Twenty individuals with medial knee osteoarthritis ( > /=2 Kellgren Lawrence grade ) were prescribed a custom laterally wedged foot orthotic device . The prescribed wedge amount was the minimal wedge amount that provided the maximum amount of pain reduction during a lateral step-down test . Following an accommodation period , all subjects returned to the laboratory for a gait analysis . Knee mechanics were collected as the subjects walked at an intentional walking speed . Walking in the laterally wedged orthotic device significantly reduced the peak adduction moment during early stance ( p < 0.01 ) compared to the nonwedged device . Similarly , the wedged orthotic device significantly reduced the knee adduction excursion from heel strike to peak adduction ( p < 0.01 ) compared to the nonwedged device . No differences in the peak adduction moment during propulsion or peak adduction during stance were observed between the orthotic conditions . A subject-specific laterally wedged orthotic device was able to reduce the peak knee adduction moment during early stance , which is thought to be associated with the progression of knee osteoarthritis . Previous studies on this device have reported issues associated with foot discomfort when using wedge amounts > 7 degrees ; however , no such issues were reported in this study . Therefore , providing a custom laterally wedged orthotic device may potentially increase compliance while still potentially reducing disease progression OBJECTIVE To compare the clinical effects of laterally wedged insoles and neutrally wedged insoles ( used as control ) in patients with medial femoro-tibial knee osteoarthritis ( OA ) . DESIGN 6-month prospect i ve r and omized controlled study . PATIENTS out patients with painful medial femoro-tibial knee OA . OUTCOME MEASURES patient 's overall assessment of disease activity ( 5 grade scale ) , WOMAC index subscales and concomitant treatments . STATISTICAL ANALYSIS Performed as an intention-to-treat analysis . Main criterion : improvement in the patient 's assessment of activity ( defined as a reduction of 1 grade or more at month 6 compared to baseline , and no intraarticular injection or lavage during the study ) . Secondary criteria for assessment : ( a ) improvement in the patient 's assessment of activity at months 1 and 3 compared to baseline , ( b ) improvement in the WOMAC subscales at months 1 , 3 and 6 , compared to baseline ( defined as an improvement of at least 30 % , and no intraarticular injection or lavage during the study ) and ( c ) concomitant therapies ( analgesics and NSAIDs ) . RESULTS The baseline characteristics of the 156 recruited patients ( 41 males , 115 females , mean age 64.8 years ) were not different in the two treatment groups . At months 1 , 3 and 6 the percentages of patients with improvement in assessment of disease activity , in WOMAC pain , joint stiffness , and physical functioning subscales were similar in the two groups . The number of days with NSAIDs intake during the previous 3 months was decreased at month 6 compared with baseline in the group furnished with laterally wedged insoles ( 14.1 days+/-28 vs 9.9 days+/-27 , P=0.04 , Wilcoxon paired test ) , while it remained unchanged in the other group ( 15.5 days+/-24 vs 15+/-28 , P=0.56 ) . Compliance and tolerance were satisfactory . Compliance was different between the two groups at month 6 , with a greater frequency of patients who wore insoles permanently in the laterally wedged insole group than in the other group ( 87.8 % vs 74.3%;P=0.032 ) . CONCLUSION This study failed to demonstrate a relevant short-term symptomatic effect of laterally-wedged insoles in medial femoro-tibial OA . However , the decrease in NSAIDs consumption together with better compliance in the treated group are in favor of a beneficial effect of laterally-wedged insoles in medial femoro-tibial OA Objective This study aim ed to determine whether the effect of laterally wedged insoles on the adduction moment in knee osteoarthritis ( OA ) declined after one month of wear , and whether higher reported use of insoles was associated with a reduced effect on the adduction moment at one month . Methods Twenty people with medial compartment OA underwent gait analysis in their own shoes wearing i ) no insoles and ; ii ) insoles wedged laterally 5 ° in r and om order . Testing occurred at baseline and after one month of use of the insoles . Participants recorded daily use of insoles in a log-book . Outcomes were the first and second peak external knee adduction moment and the adduction angular impulse , compared across conditions and time with repeated measures general linear models . Correlations were obtained between total insole use and change in gait parameters with used insoles at one month , and change scores were compared between high and low users of insoles using general linear models . Results There was a significant main effect for condition , whereby insoles significantly reduced the adduction moment ( all p < 0.001 ) . However there was no significant main effect for time , nor was an interaction effect evident . No significant associations were observed between total insole use and change in gait parameters with used insoles at one month , nor was there a difference in effectiveness of insoles between high and low users of the insoles at this time . Conclusion Effects of laterally wedged insoles on the adduction moment do not appear to decline after one month of continuous use , suggesting that significant wedge degradation does not occur over the short-term Objective To assess the effect of lateral wedge insoles compared with flat control insoles on improving symptoms and slowing structural disease progression in medial knee osteoarthritis . Design R and omised controlled trial . Setting Community in Melbourne , Australia . Participants 200 people aged 50 or more with clinical and radiographic diagnosis of mild to moderately severe medial knee osteoarthritis . Interventions Full length 5 degree lateral wedged insoles or flat control insoles worn inside the shoes daily for 12 months . Main outcome measures Primary symptomatic outcome was change in overall knee pain ( past week ) measured on an 11 point numerical rating scale . Primary structural outcome was change in volume of medial tibial cartilage from magnetic resonance imaging scans . Secondary clinical outcomes included changes in measures of pain , function , stiffness , and health related quality of life . Secondary structural outcomes included progression of medial cartilage defects and bone marrow lesions . Results Between group differences did not differ significantly for the primary outcomes of change in overall pain ( −0.3 points , 95 % confidence intervals −1.0 to 0.3 ) and change in medial tibial cartilage volume ( −0.4 mm3 , 95 % confidence interval −15.4 to 14.6 ) , and confidence intervals did not include minimal clinical ly important differences . None of the changes in secondary outcomes showed differences between groups . Conclusion Lateral wedge insoles worn for 12 months provided no symptomatic or structural benefits compared with flat control insoles . Trial registration Australian New Zeal and Clinical Trials Registry ACTR12605000503628 and Clinical Trials.gov NCT00415259 The purpose of the study was to examine the clinical efficacy of individually prescribed laterally wedged orthoses and walking shoes in the treatment of medial knee osteoarthritis using a prospect i ve , single-blind , block-r and omized controlled design . Sixty-six subjects ( 29 males , 37 females , mean age 62.4 years , mean BMI 33.0 kg/m(2 ) ) were block-r and omized to a lateral wedge ( treatment ) or neutral ( control ) orthotic group . Both groups were issued a st and ardized walking shoe for use with the orthoses . Primary outcome measures included the pain , stiffness , and functional limitations subscales of the Western Ontario and McMaster Universities index . Secondary outcome measures included the 6-minute walk distance and pain change , and stair negotiation time and pain change . A significant interaction ( p=0.039 ) favoring the treatment group was observed for pain change during the 6-minute walk . The treatment group demonstrated significant improvements at both 1 month ( p<0.001 ) and 1 year ( p<0.001 ) compared to baseline . The control group only demonstrated significant improvements at 1 year ( p=0.017 ) . No other interactions were observed . Both groups were improved at each follow-up in the WOMAC subscales for pain ( p<0.001 ) , stiffness ( p<0.001 ) , and physical function ( p<0.001 ) . Both groups also improved in 6-minute walk test distance ( p<0.001 ) , stair negotiation test time ( p=0.004 ) , and stair negotiation test pain change ( p<0.001 ) . The results suggest that both neutral and laterally wedged orthoses may be beneficial in the management of medial knee osteoarthritis when used with walking shoes . However , the addition of lateral wedging was associated with early improvements in 6-minute walk test pain change not seen in the control group OBJECTIVE To compare the clinical effects of laterally wedged insoles and neutrally wedged insoles ( used as control ) in patients with medial femoro-tibial knee osteoarthritis . METHODS STUDY DESIGN 24-month prospect i ve r and omized controlled study . PATIENTS Out patients with painful medial femoro-tibial knee osteoarthritis . OUTCOME MEASURES Patient 's overall assessment of disease activity ( 5 grade scale ) , WOMAC index subscales and concomitant treatments . STATISTICAL ANALYSIS Performed as an intention-to-treat analysis , with the last observation carried forward ( LOCF ) . Main symptomatic criterion : Improvement in the patient 's assessment of activity ( defined as a reduction of one grade or more at the end of the study as compared to baseline , and no intra-articular injection or lavage during the 6 months previous to the last visit ) . Secondary criteria for assessment : ( a ) Changes in the WOMAC subscales at month 24 , and ( b ) concomitant therapies ( analgesics , NSAIDs and intra-articular injections or lavages ) . Structural criterion : Joint space width ( JSW ) at the narrowest point . Non-compliance was defined as intermittent or lack of insole fitting at two consecutive visits . Compliance within groups was compared by using a life table analysis technique ( Log-Rank ) . RESULTS The baseline characteristics of the 156 recruited patients ( 41 males , 115 females , mean age 64.8 years ) were not different in the 2 treatment groups . At year 2 , there was no statistically significant difference between the 2 groups concerning the percentages of patients with improvement in both global assessment of disease activity and in WOMAC subscales ( pain , stiffness , function ) . The number of days with NSAIDs intake was lower in the group with laterally wedged insoles than in the neutrally wedged group ( 71+/-173 days vs. 127+/-193 days , P=0.003 , Mann-Whitney test ) . The mean joint space narrowing rate did not differ between the two groups : 0.21+/-0.59 mm/year in the laterally wedged group vs 0.12+/-0.32 mm/year in the neutrally wedged group . Compliance and tolerance were satisfactory . Compliance was different between the 2 groups at month 24 , with a greater frequency of patients who wore insoles permanently in the laterally wedged insole group than in the other group ( 85.8 % vs 71.9 % , P=0.023 ) . CONCLUSION This study failed to demonstrate a relevant symptomatic and /or structural effect of laterally-wedged insoles in medial femoro-tibial OA . However , the reduced NSAIDs intake and the better compliance in the treatment group are in favor of a beneficial effect of laterally-wedged insoles in medial femoro-tibial OA CONTEXT Knee osteoarthritis ( OA ) is a leading cause of disability in older persons . Few risk factors for disease progression or functional decline have been identified . Hip-knee-ankle alignment influences load distribution at the knee ; varus and valgus alignment increase medial and lateral load , respectively . OBJECTIVE To test the hypotheses that ( 1 ) varus alignment increases risk of medial knee OA progression during the subsequent 18 months , ( 2 ) valgus alignment increases risk of subsequent lateral knee OA progression , ( 3 ) greater severity of malalignment is associated with greater subsequent loss of joint space , and ( 4 ) greater burden of malalignment is associated with greater subsequent decline in physical function . DESIGN AND SETTING Prospect i ve longitudinal cohort study conducted March 1997 to March 2000 at an academic medical center in Chicago , Ill. PARTICIPANTS A total of 237 persons recruited from the community with primary knee OA , defined by presence of definite tibiofemoral osteophytes and at least some difficulty with knee-requiring activity ; 230 ( 97 % ) completed the study . MAIN OUTCOME MEASURES Progression of OA , defined as a 1- grade increase in severity of joint space narrowing on semiflexed , fluoroscopically confirmed knee radiographs ; change in narrowest joint space width ; and change in physical function between baseline and 18 months , compared by knee alignment at baseline . RESULTS Varus alignment at baseline was associated with a 4-fold increase in the odds of medial progression , adjusting for age , sex , and body mass index ( adjusted odds ratio [ OR ] , 4.09 ; 95 % confidence interval [ CI ] , 2.20 - 7.62 ) . Valgus alignment at baseline was associated with a nearly 5-fold increase in the odds of lateral progression ( adjusted OR , 4.89 ; 95 % CI , 2.13 - 11.20 ) . Severity of varus correlated with greater medial joint space loss during the subsequent 18 months ( R = 0.52 ; 95 % CI , 0.40 - 0.62 in dominant knees ) , and severity of valgus correlated with greater subsequent lateral joint space loss ( R = 0.35 ; 95 % CI , 0.21 - 0.47 in dominant knees ) . Having alignment of more than 5 degrees ( in either direction ) in both knees at baseline was associated with significantly greater functional deterioration during the 18 months than having alignment of 5 degrees or less in both knees , after adjusting for age , sex , body mass index , and pain . CONCLUSION This is , to our knowledge , the first demonstration that in primary knee OA varus alignment increases risk of medial OA progression , that valgus alignment increases risk of lateral OA progression , that burden of malalignment predicts decline in physical function , and that these effects can be detected after as little as 18 months of observation Study Design . A critical appraisal of the literature . Objectives . To increase awareness of the importance of applicability and clinical relevance of the results of r and omized controlled trials ( RCTs ) in the field of spinal disorders by formulating a list of items for assessment of applicability and clinical relevance of results of RCTs . Summary of Background Data . In systematic review s of r and omized controlled trials ( RCTs ) , critical appraisal of method ologic quality is considered important . Less attention has been paid to the assessment of the applicability and the clinical relevance of the results . Methods . RCTs in an up date of the Cochrane review on exercise therapy for low back pain were used . Most of the trials did not score positively on the five Cochrane Back Review Group basic items describing patients : intervention and setting , outcome , effect size , and benefits related to adverse effects . Item 1 was met by 88 % of the trials , but item 2 only by 51 % , item 3 by 67 % , item 4 by 35 % , and item 5 by 0 % . Subsequently , a more comprehensive list of items for the assessment of applicability and clinical relevance of results of RCTs was developed . These criteria were pilot tested on the RCTs . After pilot testing and a subsequent consensus meeting , the list of items was drafted and circulated among the members of the Editorial Board of the Cochrane Back Review Group . Changes were made in response to comments . Results . The final list consists of 40 items . The items are ordered on two headings : Does the report enable the assessment of applicability ? Are the study results clinical ly relevant ? We present examples of informative and noninformative reporting of RCTs in order to illustrate how information on applicability and clinical relevance of results can be assessed . Conclusions . Authors of RCTs should adequately report on items that are essential to assess the applicability and clinical relevance of results . The presented list of items may help clinicians reading RCTs and authors of systematic review s to draw more balanced conclusions on applicability and clinical relevance of results OBJECTIVE To assess immediate effects of laterally wedged insoles on walking pain , external knee adduction moment , and static alignment , and whether these immediate effects together with age , body mass index , and disease severity predict clinical outcome after 3 months of wearing insoles in medial knee osteoarthritis . METHODS Forty volunteers ( mean age 64.7 years , 16 men ) were tested in r and om order with and without a pair of 5 degrees full-length lateral wedges . Immediate changes in static alignment were measured via radiographic mechanical axis and changes in adduction moment via 3-dimensional gait analysis . After 3 months of treatment with insoles , changes in pain and physical functioning were assessed via the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and patient-perceived global change scores . RESULTS Reductions in the adduction moment occurred with insoles ( first peak mean [ 95 % confidence intervals ( 95 % CI ) ] -0.22 [ -0.28 , -0.15 ] Nm/body weight x height % ) , accompanied by a reduction in walking pain of approximately 24 % ( mean [ 95 % CI ] -1.0 [ -4.0 , 2.0 ] ) . Insoles had no mean effect on static alignment . Mean improvement in WOMAC pain ( P = 0.004 ) and physical functioning ( mean [ 95 % CI ] -6 [ -11 , -1 ] ) was observed at 3 months , with 25 ( 69 % ) and 26 ( 72 % ) of 36 individuals reporting global improvement in pain and functioning , respectively . Regression analyses demonstrated that disease severity , baseline functioning , and magnitude of immediate change in walking pain and the first peak adduction moment with insoles were predictive of clinical outcome at 3 months . CONCLUSION Lateral wedges immediately reduced knee adduction moment and walking pain but had no effect on static alignment . Although some parameters predicted clinical outcome , these explained only one-third of the variance , suggesting that other unknown factors are also important OBJECTIVE To compare the influence of concomitant heeled footwear when wearing a lateral wedged insole for medial compartment of osteoarthritis ( OA ) of the knee , between everyday walking shoes for outdoor use and socks or flat footwear without a heel for indoor use . DESIGN A total of 227 out patients were prospect ively r and omized and treated with a neutral wedged insole inserted into shoes ( placebo with shoes ; n=45 ) , a wedged insole inserted into shoes ( inserted insole with shoes ; n=45 ) , a sock-type ankle supporter with a wedged insole when wearing socks or flat footwear ( inserted insole without shoes ; n=46 ) , a subtalar strapped insole when wearing shoes ( strapped insole with shoes ; n=45 ) , and the strapped insole with socks or flat footwear ( strapped insole without shoes ; n=46 ) . The Lequesne index of knee OA at week 12 was compared with the baseline in each treatment group . RESULTS Twenty patients withdrew from the study , and the 207 patients who completed the 12-week study were evaluated . At the final assessment , participants wearing the inserted insole without shoes ( P=0.003 ) , the strapped insole with shoes ( P<0.0001 ) , and the strapped insole without shoes ( P<0.0001 ) demonstrated significantly improved Lequesne index scores in comparison with their baseline assessment s. No significant differences were found in the placebo ( P=0.16 ) or the inserted insole with shoes ( P=0.2 ) groups . CONCLUSION Concomitant heeled footwear may decrease the efficacy of an inserted lateral wedged insole . The optimal usage of a lateral wedged insole for knee OA would be the combination with socks or flat footwear without heels OBJECTIVE To determine the effects of lateral wedged insoles on knee kinetics and kinematics during walking , according to radiographic severity of medial compartment knee osteoarthritis ( OA ) . DESIGN A prospect i ve case control study of patients with medial compartment OA of the knee . SETTING Gait analysis laboratory in a university hospital . PARTICIPANTS Forty-six medial compartment knees with OA of 23 patients with bilateral disease and 38 knees of 19 age-matched healthy subjects as controls . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES We measured the peak external adduction moment at the knee during the stance phase of gait and the first acceleration peak after heel strike at the lateral side of the femoral condyles . Kellgren and Lawrence grading system was used for radiographic assessment of OA severity . RESULTS The mean value of peak external adduction moment of the knee was higher in OA knees than the control . Application of lateral wedged insoles significantly reduced the peak external adduction moment in Kellgren-Lawrence grade s I and II knee OA patients . The first acceleration peak value after heel strike in these patients was relatively high compared with the control . Application of lateral wedged insoles significantly reduced the first acceleration peak in Kellgren-Lawrence grade s I and II knee OA patients . CONCLUSIONS The kinetic and kinematic effects of wearing of lateral wedged insoles were significant in Kellgren-Lawrence grade s I and II knee OA . The results support the recommendation of use of lateral wedged insoles for patients with early and mild knee OA OBJECTIVE The adduction moment at the knee during gait is the primary determinant of medial-to-lateral load distribution . If the adduction moment contributes to progression of osteoarthritis ( OA ) , then patients with advanced medial tibiofemoral OA should have higher adduction moments . The present study was undertaken to investigate the hypothesis that the adduction moment normalized for weight and height is associated with medial tibiofemoral OA disease severity after controlling for age , sex , and pain level , and to examine the correlation of serum hyaluronan ( HA ) level with disease severity and with the adduction moment in a subset of patients . METHODS Fifty-four patients with medial tibiofemoral OA underwent gait analysis and radiographic evaluation . Disease severity was assessed using the Kellgren-Lawrence ( K-L ) grade and medial joint space width . In a subset of 23 patients with available sera , HA was quantified by s and wich enzyme-linked immunosorbent assay . Pearson correlations , a r and om effects model , and multivariate regression models were used . RESULTS The adduction moment correlated with the K-L grade in the left and right knees ( r = 0.68 and r = 0.60 , respectively ) , and with joint space width in the left and right knees ( r = -0.45 and r = -0.47 , respectively ) . The relationship persisted after controlling for age , sex , and severity of pain . The partial correlation between K-L grade and adduction moment was 0.71 in the left knees and 0.61 in the right knees . For every 1.0-unit increase in adduction moment , there was a 0.63-mm decrease in joint space width . In the subset of patients in whom serum HA levels were measured , HA levels correlated with medial joint space width ( r = -0.55 ) , but not with the adduction moment . CONCLUSION There is a significant relationship between the adduction moment and OA disease severity . Serum HA levels correlate with joint space width but not with the adduction moment . Longitudinal studies will be necessary to determine the contribution of the adduction moment , and its contribution in conjunction with metabolic markers , to progression of medial tibiofemoral OA OBJECTIVE In uncontrolled studies , a lateral-wedge insole has reduced knee pain in patients with medial knee osteoarthritis ( OA ) . The aim of this study was to test the efficacy of this simple , low-cost intervention for pain in patients with medial knee OA . METHODS We conducted a double-blind , r and omized , crossover trial design ed to detect a small effect of treatment . Participants were at least 50 years of age and had medial joint space narrowing on posteroanterior semiflexed radiographs and scores indicating moderate pain for 2 of the 5 items on the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain scale . Participants were r and omized to receive a 5 degrees lateral-wedge insole or a neutral insole for 6 weeks . Following a 4-week washout period , participants crossed over to the other treatment for 6 weeks . Knee pain , the primary outcome , was assessed by the WOMAC pain scale ( visual analog scale version ) . Secondary outcomes included the WOMAC disability subscale , overall knee pain , 50-feet walk time , chair-st and time , and use of medications for knee pain . RESULTS Ninety patients were r and omized . The mean difference in pain between the 2 treatments was 13.8 points on the WOMAC pain scale ( 95 % confidence interval -3.9 , 31.4 [ P=0.13 ] ) . We observed similar small effects for the secondary outcomes . CONCLUSION The effect of treatment with a lateral-wedge insole for knee OA was neither statistically significant nor clinical ly important OBJECTIVE To develop clinical practice guidelines for the use of foot orthotics ( FO ) in the treatment of knee and hip osteoarthritis . METHOD The SOFMER ( French Physical Medicine and Rehabilitation Society ) methodology , associating a systematic review of the literature , input from every day clinical practice and external review by a multidisciplinary expert committee , was used . The selected analysis criteria were pain , disability , medications used and X-ray evolution of osteoarthritis . The recommendations are classified according to the level of proof in Grade A , B or C according to the French National Agency for Health Accreditation and Evaluation ( NAHAE ) . RESULTS In medial knee osteoarthritis , foot pronation orthotics -- when there are no contraindications -- can be proposed for their symptomatic impact , especially in the decrease of NSAIDs consumption ( Grade B ) . To this day , there is no evidence of a structural or functional impact on osteoarthritis ( Grade B ) . Outside of this specific clinical framework , there is no vali date d indication for prescribing foot orthotics in the treatment of knee or hip OA ( Grade C ) . CONCLUSION It is necessary to have further r and omized controlled trials to better define the indication of Foot orthotics ( severity of knee OA , genu varum ) , test the efficacy of other orthoses such as cushioning FO . The long-term side effects , mainly on the external femorotibial compartment could also be assessed . A medical and economical assessment of FO prescriptions is also quite necessary Kakihana W , Torii S , Akai M , Nakazawa K , Fukano M ; Naito K : Effect of a lateral wedge on joint moments during gait in subjects with recurrent ankle sprain . Am J Phys Med Rehabil 2005;84:858 - 864 . This study assessed the biomechanic effects of wearing a lateral wedge on the subtalar joint moment during gait in athletes with and without an unstable lateral ankle . A crossover design was applied whereby 50 collegiate males walked with two different wedges : a 0 ° control wedge and a 6 ° lateral wedge . We investigated frontal plane angles and moments at the subtalar joint and the knee joint , as well as ground reaction forces and center of pressure excursion . Moments were derived using a three-dimensional inverse dynamics model of the lower extremity . The 6 ° lateral wedge significantly increased the subtalar joint valgus moment ( P < 0.001 ) and reduced the knee joint varus moment ( P < 0.001 ) when compared with no wedge . The differences between wedge conditions were associated with a laterally shifted location of the center of pressure during stance phase . However , there were diverse , sometimes reversed effects with the wedge among the athletes with an unstable lateral ankle . These results indicate that biomechanical indications and limitations of lateral wedges in unstable lateral ankles should be analyzed in more detail , possibly leading to new guidelines for the use of such foot orthoses |
705 | 21,286,935 | Conclusions We demonstrate that methane present on breath testing is significantly associated with constipation in both IBS and functional constipation .
These results suggest there may be merit in using breath testing in constipation .
Moreover , methane may be used to identify c and i date s for antibiotic treatment of constipation | Background A growing body of literature suggests an association between methane and constipation .
Studies also link degree of methane production to severity of constipation and have shown constipation is improved following antibiotics .
Aims We aim to conduct a systematic review and meta- analysis to examine the cumulative evidence regarding the association between methane and constipation . | Context Few trials have evaluated the effects of antibiotics on symptoms of the irritable bowel syndrome ( IBS ) . Contribution In this double-blind trial , 87 patients with IBS were r and omly assigned to either rifaximin ( 400 mg 3 times daily ) or placebo for 10 days . Over a 10-week follow-up period , the rifaximin recipients reported global improvements in overall symptoms and less bloating more frequently than the placebo recipients . No major differences in abdominal pain , diarrhea , or constipation were observed between the groups . Caution s The duration of therapy and follow-up was short . Implication s Rifaximin may improve some symptoms in some patients with IBS . The Editors The irritable bowel syndrome ( IBS ) is one of the most common chronic medical conditions ( 16 ) , yet its cause is unknown . Among other contributors , alterations in gut flora have been identified as potentially important . Results of recent studies indicate that up to 84 % of patients with IBS have an abnormal lactulose breath test result , suggesting small-intestinal bacterial overgrowth ( 7 , 8) . On the basis of this concept , the antibiotic neomycin can statistically significantly improve the symptoms of IBS ( 7 , 8) . In addition , the effect of neomycin correlates with the elimination of bacterial overgrowth , as indicated by the normalization of the lactulose breath test result ( 7 , 8) . Although neomycin seems to improve symptoms , it effectively eliminates bacterial overgrowth in only about 25 % of patients with IBS ( 8) . Furthermore , side effects limit the use of neomycin . Low efficacy also applies to other antibiotics ( for example , doxycycline and amoxicillinclavulanate ) that have been previously investigated for treating bacterial overgrowth ( 9 ) . An ideal antibiotic for IBS is , arguably , one with negligible systemic absorption , minimal side effects , and high efficacy for bacterial overgrowth . Rifaximin is a gut-selective antibiotic with negligible systemic absorption ( 0.4 % ) and broad-spectrum activity in vitro against gram-positive and gram-negative aerobes and anaerobes ( 10 ) . On the basis of this broad spectrum , eradication rates with rifaximin in bacterial overgrowth are as high as 70 % ( 11 ) . Furthermore , rifaximin has a similar tolerability profile to that of placebo and has known activity against Clostridium difficile ( 12 ) . These properties make it a good c and i date for treating a condition that is as common as IBS . Our study aim ed to determine whether the nonabsorbed antibiotic rifaximin is more effective than placebo in reducing symptoms in adults with IBS . Methods Setting and Participants Our study was conducted at the Cedars-Sinai Medical Center , Los Angeles , California , and the University of Chicago , Chicago , Illinois . We recruited patients with IBS through advertising in local media ( radio and news publications ) . We did not recruit patients from the IBS clinics of the Cedars-Sinai Gastrointestinal Motility Program to avoid enrollment of tertiary care patients . The institutional review board of both centers approved the study , and all patients provided written informed consent . Patients between 18 and 65 years of age who met Rome I criteria ( 13 ) were eligible . Exclusion criteria were the presence of underlying conditions that are known to predispose to bacterial overgrowth , including diabetes ; narcotic use ; previous bowel resection ; inflammatory bowel disease ; cirrhosis ; known bowel adhesions ; or any known chronic gastroenterological disease , such as celiac disease . We excluded patients who were taking tegaserod and antidepressants unless these treatments were discontinued before study entry . We also excluded participants who reported taking an oral antibiotic within the previous 3 months . After participant inclusion and exclusion , we recruited 84 participants from the Cedars-Sinai Medical Center and 3 participants from the University of Chicago . We followed participants in special research clinics at both centers . R and omization and Interventions Eligible patients completed a 7-day stool diary that was based on the Bristol stool form scale ( 14 ) . Patients returned to the clinic after a 12-hour fast and completed a symptom question naire about the preceding 7 days of symptoms . We then r and omly assigned patients to double-blind treatment with 400 mg of rifaximin 3 times daily for 10 days or a matching placebo . We chose this dosage on the basis of a previous study that demonstrated the efficacy of rifaximin in bacterial overgrowth ( 11 ) . The r and omization of rifaximin versus placebo was conducted outside of Cedars-Sinai Medical Center in a 1:1 ratio into blocks of 4 patients . The allocation sequence was determined and coded at Salix Pharmaceuticals , Morrisville , North Carolina . Since this was an investigator-initiated study , the rifaximin and placebo were distributed to the Cedars-Sinai Medical Center , and nonstratified medicine and placebo were sent to the University of Chicago in groups of 4 as enrollment progressed . The medicine and placebo were prepackaged to conceal content at all times . Research personnel who were involved in product distribution were also blinded to package content . Assessment s and Follow-up After completing the 10-day course of study medication , patients immediately began another stool diary for 7 days then returned to complete a follow-up question naire and to return their pill container for a pill count to determine adherence . Patients then entered the follow-up phase , during which they completed a weekly self-administered symptom question naire at home that documented their symptoms for an additional 9 weeks ( for a total of 10 weeks of post-treatment follow-up ) . During this time , we asked participants to fax their responses to the research office . When a fax was not received on the appropriate day , research assistants called patients to ensure adherence . During this phase of study , no physician interaction occurred . During the last week of follow-up , patients completed a daily stool diary . At the end of the follow-up period , patients returned to the clinic for a final visit , which included another symptom question naire . For the initial symptom question naire , patients were asked to indicate the severity of each of 9 symptoms ( abdominal pain , diarrhea , constipation , bloating , urgency , incomplete evacuation , mucus , sense of incomplete evacuation , and gas ) on a visual analogue scale ( VAS ) ranging from 0 mm to 100 mm , with 100 mm being extreme . We used all 9 symptoms to verify IBS criteria in patients , but we assigned only diarrhea , constipation , abdominal pain , and bloating a priori as treatment end points . We asked patients to rate the severity of their symptoms on the VAS again 7 days after the completion of rifaximin treatment or placebo . Furthermore , we asked patients to provide a percentage of global improvement in their overall IBS symptoms from 0 % to 100 % . We chose global improvement since the Rome Consensus Group considers it to be the preferred end point measure in IBS treatment studies ( 15 ) . Patients then rated the severity of their symptoms on the VAS and rated global improvement again each week for 8 weeks of follow-up and at the final visit to provide a total of 10 weeks of follow-up data . Table 1 depicts the number of patients with outcomes at various time points during the study . Table 1 . Study Recruitment and Enrollment Summary At the first follow-up visit , physicians evaluated adverse events by asking patients , in an open-ended manner , whether they had experienced adverse events while receiving therapy and to elaborate on any that occurred . Although breath testing and breath methane level determinations were performed , we do not report them in our paper . Statistical Analysis We determined the number of patients for the study on the basis of the neomycin effect in a recent double-blind study for IBS on global improvement ( 8) . To detect a difference of 35 % ( SD , 50 % ) with a power of 90 % , we needed to assign 44 participants per group . Assuming a dropout rate of 10 % , we calculated that approximately 96 patients would need to be recruited . The primary end point was global improvement in IBS symptoms during follow-up . As seen in Figure 1 , data were not available for all 10 weeks of follow-up . Figure 1 . Study flow chart . We assessed the primary end point ( percentage of global improvement ) across the 10 weeks of follow-up by using an approach analogous to a repeated measures analysis of variance . Specifically , we used a mixed model with visit week ( at 10 levels ) , treatment group ( rifaximin or placebo ) , and group-by-week interaction as the fixed factors and patient as the r and om factor . The interaction and group factors were the main factors of interest in the analyses . We estimated mixed models by using the restricted maximum likelihood method . Because the global improvement percentage varied widely across week for most individuals , we considered week to be a categorical variable in the mixed model . Within-patient correlation across time was addressed by an autoregressive ( first-order ) model for the covariance structure . Missing data were mostly intermittent , and we assumed them to be missing at r and om . The normality assumption was rarely satisfied in either group at any week . However , at least 34 observations were recorded per group per week and the sample sizes were well-balanced , so we used the mixed-model analysis . We analyzed models with a single covariate ( baseline diarrhea , constipation , abdominal pain , or bloating severity score ) . The covariate models did not improve the fit nor did they change the substantive results . Hence , we presented the simpler ( no covariate ) model results . We used a similar mixed-model approach to assess the secondary end points of abdominal pain , bloating , diarrhea , and constipation . Within-patient correlation was modeled by an autoregressive covariance structure . The normality assumption was rarely satisfied for the diarrhea outcome , with a similar floor effect for the primary outcome Abstract The relationship between methanogenic flora and hydrogen ( H2 ) production is considered to be a possible confounding factor in the interpretation of hydrogen breath tests ( H2BT ) . Therefore , the present study was conducted prospect ively and included 154 IBS patients ( fulfilling Rome II criteria ) and 286 age- and -sex-matched apparently healthy controls . Each subject underwent H2BT after overnight fasting using 25 g lactose . Methane and H2 were measured using an SC Microlyser from Quintron , USA , at baseline and every 30 min for a total of 4 h. Subjects with fasting methane concentration < 10 ppm were labeled as low methane producers ( LMP ) and > 10 ppm as predominant methane producers ( PMP ) . A rise > 20 ppm over base line in hydrogen concentration was taken as + ve hydrogen breath test . IBS and control groups included 66.78 % and 67.53 % males , respectively . Mean age in the two groups were 48.52 ± 30.54 years ( range 15–68 years ) and 45.67 ± 30.54 years ( range 15–78 years ) , respectively . Hydrogen breath test was + ve in 77/154 ( 50 % ) IBS patients and in 142/286 ( 49.65 % ) in controls ( P > 0.05 ) . It was also observed that the hydrogen breath test was −ve due to PMP in 5/77 ( 6.49 % ) of IBS patients and in 29/154 ( 20.14 % ) in controls . PMP affected lactose hydrogen breath tests in 6.49–20.14 % subjects . This effect is more apparent in apparently healthy subjects as compared to patients with IBS PURPOSE Small intestinal bacterial overgrowth ( SIBO ) may coexist with irritable bowel syndrome ( IBS ) and eradication therapy has been reported as effective in reducing IBS symptoms . Aims of this study were to : ( 1 ) Assess the clinical profiles of IBS patients , who underwent breath testing with a glucose substrate -- glucose breath test ( GBT ) ; ( 2 ) Evaluate hydrogen and methane parameters in various IBS groups ; ( 3 ) Assess the role of inhibition of gastric acid in contributing to SIBO ; ( 4 ) Investigate efficacy and safety of non-absorbable antibiotic rifamixin for eradication and symptom relief . METHODS 204 IBS patients met the ROME II criteria for IBS ( 170F & 34 M ; mean age 46.4 ; range 18 - 88 ) and underwent GBT . 8 of these patients with positive GBT were treated with rifaximin 200 mg , 4 times a day for 1 month and symptom assessment s and GBT were repeated . RESULTS 93 ( 46 % ) had a positive GBT . 68 ( 73 % ) of these 93 IBS-diarrhea dominant ( IBS-D ) , 12 ( 13 % ) were constipation dominant ( IBS-C ) and 13 ( 14 % ) IBS with alternating bowel pattern . 48 % of SIBO positive patients were receiving PPI therapy compared to 40 % of IBS patients with negative GBT . 61 ( 66 % ) produced only hydrogen , 27 ( 29 % ) methane only , and 5 ( 5 % ) both-hydrogen and methane . There were more methane producers in IBS-C then IBS-D group ( 58 % vs 28 % ) while IBS-D had more hydrogen formers ( 71 % vs 42 % ) . 8 patients with SIBO ( 7F & IM ; mean age 55 , range 31 - 85 ) received rifamixin 800 mg/day . Repeat GBT was normal in 6 ( 75 % ) , 1 patient ( 12.5 % ) normalized according to hydrogen criteria but methane remained positive . Symptoms score improved in 7 ( 87.5 % ) patients and no adverse events were noted . CONCLUSIONS ( 1 ) SIBO was present in nearly half of this large cohort of IBS patients based on the results of GBT ; ( 2 ) Chronic PPI use was not associated with SIBO ; ( 3 ) Methane formers on the GBT are more likely to be constipated ; ( 4 ) Rifaximin is effective in treatment of SIBO in IBS and controlled trials are warranted BACKGROUND : Recent work has demonstrated that among irritable bowel syndrome ( IBS ) subjects , methane on lactulose breath test ( LBT ) is nearly universally associated with constipation predominance . This work has been based on subjective constipation outcomes . In this study , methane is compared to constipation in another population of IBS subjects with constipation being determined both subjectively and objective ly . METHODS : A nested study was conducted in subjects enrolled in a double-blind r and omized placebo-controlled study . After consent , subjects were asked to complete a stool diary for 7 days . This included logging of all bowel movements that week as well as documenting the stool consistency for each during the same period using the Bristol Stool Score . After 7 days , subjects were asked to rate their symptoms on a visual analogue scale ( VAS ) score ( 0–100 mm ) for diarrhea and constipation . They then had an LBT to evaluate both methane and hydrogen profiles over 180 min . Subjects with methane were compared to those without methane for Bristol Stool Score , stool frequency , as well as VAS scores for diarrhea and constipation . The degree of constipation was then compared to the quantity of methane production on LBT based on area under the curve . RESULTS : Among 87 subjects , 20 ( 23.8 % ) produced methane . IBS subjects with methane had a mean constipation severity of 66.1 ± 36.7 compared to 36.2 ± 30.8 for nonmethane producers ( P < 0.001 ) . The opposite was noted for diarrhea ( P < 0.01 ) . On LBT , the quantity of methane seen on breath test was directly proportional to the degree of constipation reported ( r = 0.60 , P < 0.01 ) . In addition , greater methane production correlated with a lower stool frequency ( r = −0.70 , P < 0.001 ) and Bristol Stool Score ( r = −0.58 , P < 0.01 ) . CONCLUSION : Methane on LBT is associated with constipation both subjectively and objective ly . The degree of methane production on breath test appears related to the degree of constipation BACKGROUND Irritable bowel syndrome ( IBS ) is a common health problem affecting a substantial proportion of the population . Many individuals with symptoms of IBS do not seek medical attention or have stopped consulting because of disillusionment with current treatment options . Such patients may choose to re-consult with the advent of new therapies with a result ing impact on health services . AIM To generate reliable estimates of the prevalence of IBS by age , sex and symptom group . DESIGN OF STUDY Postal survey . SETTING Patients selected from registers of eight general practice s in north and west Birmingham . METHOD Eight thous and six hundred and forty-six patients aged > or=18 years were r and omly selected from practice lists . Selected patients received a question naire , which included diagnostic criteria for IBS . A second question naire , seeking more detailed information , was sent to those whose responses indicated the presence of IBS symptoms . RESULTS Of the 8386 patients surveyed 4807 ( 57.3 % ) useable replies were received . The community-based prevalence of IBS was 10.5 % ( 6.6 % of men and 14.0 % of women ) . Overall the symptom profiles were characterised by diarrhoea ( 25.4 % ) , constipation ( 24.1 % ) and alternating symptoms ( 46.7 % ) . Over half ( 56 % ) of all patients had consulted their general practitioner within the past 6 months and 16 % had seen a hospital specialist . A quarter of patients consulted more than twice and 16 % were referred to secondary care ; almost half were on prescribed medication . However , the majority of patients were self-treated . Less than half of those currently reporting symptoms of IBS according to the Rome II criteria had received a diagnosis of IBS . Reduced quality of life and a previous diagnosis of a stomach ulcer were identified as predictors of consultation . CONCLUSION Quality of life was significantly reduced in patients with IBS . There is a substantial burden on primary healthcare services despite over half of those with symptoms also self- medicating . The Rome II diagnostic criteria identified those most affected by their symptoms and are a valid clinical tool . Population -based health surveys will need to supplement the Rome criteria with questions aim ing to identify patients formally diagnosed but whose symptoms are currently under control if prevalence is to be reliably estimated Studies suggest that subjects with IBS have altered gut flora . Among these findings , methane production is more commonly associated with constipation-predominant symptoms . In this study , we prospect ively evaluated the role of methane as a diagnostic test . Consecutive Rome I positive IBS patients referred for a lactulose breath test were eligible to participate . After exclusion criteria , subjects completed a symptom question naire grading bloating , diarrhea , and constipation on a VAS scale ( 0–100 mm ) . Once completed , a physician interviewed the subjects and rated the subject accordingly , and also determined whether the patient had C-IBS , D-IBS , or neither . Subjects and physicians were blinded to the results of the breath test . The presence of methane in the breath test was compared to the results of the scoring by subjects and physicians . A total of 56 Rome I positive IBS subjects were enrolled . During breath testing , 28 subjects produced methane . Good agreement between physician ’s evaluation and the patient ’s was seen ( diarrhea = 0.69 ; constipation = 0.69 ; bloating = 0.62 ) . The severity of constipation was noted to be greater in the methane group ( 49.3 ± 28.7 ) than in the non-methane group ( 25.3 ± 31.47 ) ( P < 0.01 ) . In contrast , diarrhea was less severe in the methane group ( 12.3 ± 21.0 ) than the non-methane group ( 36.7 ± 32.4 ) ( P < 0.01 ) . Out of the 56 patients , 23 C-IBS subjects were identified by the physician . When methane was used to predict the assignment of C-IBS compared to non-C-IBS , it had a sensitivity of 91.7 % and a specificity of 81.3 % ( OR = 47.7 , CI = 9.4–232 , P < 0.00001 ) . In conclusion , methane is a potential diagnostic test for the identification of C-IBS and may guide treatment AIMS : To study the efficacy of rifaximin , a nonabsorbable antibiotic , in relieving chronic functional symptoms of bloating and flatulence . METHODS : R and omized double-blind placebo-controlled trial consisting of three 10-day phases : baseline ( phase 1 ) , treatment with rifaximin 400 mg b.i.d . or placebo ( phase 2 ) , and post-treatment period ( phase 3 ) . Primary efficacy variable was subjective global symptom relief at the end of each phase . A symptom score was calculated from a symptom diary . Lactulose H2-breath test ( LHBT ) was performed at baseline and end of study . RESULTS : One hundred and twenty-four patients were enrolled ( 63 rifaximin and 61 placebo ) . Baseline characteristics were comparable and none had an abnormal baseline LHBT . Rome II criteria were met in 58.7 % and 54.1 % , respectively . At the end of phase 2 , there was a significant difference in global symptom relief with rifaximin versus placebo ( 41.3%vs 22.9 % , p= 0.03 ) . This improvement was maintained at the end of phase 3 ( 28.6%vs 11.5 % , p= 0.02 ) . Mean cumulative and bloating-specific scores dropped significantly in the rifaximin group ( p < 0.05 ) . Among patients with IBS , a favorable response to rifaximin was noted ( 40.5%vs 18.2 % ; p= 0.04 ) persisting by the end of phase 3 ( 27%vs 9.1 % ; p= 0.05 ) . H2-breath excretion dropped significantly among rifaximin responders and correlated with improvement in bloating and overall symptom scores ( p= 0.01 ) . No adverse events were reported . CONCLUSIONS : Rifaximin is a safe and effective treatment for abdominal bloating and flatulence , including in IBS patients . Symptom improvement correlates with reduction in H2-breath excretion . Future trials are needed to examine the efficacy of long-term or cyclic rifaximin in functional colonic disorders Objective : To assess the effects of drug-induced changes in mean transit time ( MTT ) on the activity of human fecal flora in vitro . Methods : The activity of fecal flora was estimated by the ability of a fecal inoculum to ferment a substrate ( beet fiber ) in vitro in a batch system for 24 h. The inoculum was collected from 8 healthy volunteers studied during three 3-week r and omized periods , who received a controlled diet alone ( control period ) or the same diet with either cisapride or loperamide . Cisapride and loperamide were adjusted in order to halve and double MTT measured during the control period . At the end of each period , the percentage disappearance of the initial added substrate and the concentration and the profile of short-chain fatty acids ( SCFAs ) , were determined . Results : In the control period , the pH of the inoculum and SCFA concentration were inversely related to MTT ( P=0.0001 ) . Individual SCFA production was also significantly related to MTT ( P<0.01 ) . Cisapride-reduced transit time was associated with a significant rise in the concentrations of total SCFAs ( P<0.05 ) , propionic and butyric acids ( P<0.05 ) and the percentage substrate disappearance ( P<0.05 ) . Inverse relations were observed during the loperamide period . Moreover , MTT was inversely related to the percentage substrate disappearance ( P<0.001 ) , SCFA production ( P<0.001 ) and butyrate production ( P<0.0005 ) . Conclusion : Changes in MTT alter bacterial activity and modify the bacterial pathways affecting the proportion of individual SCFAs . Sponsorship : This research was supported in part by Eridania Béghin-Say and by a grant from the French Ministry for Research ( Aliment Demain contract no. G 92 G 0554 ) European Journal of Clinical Nutrition ( 2000 ) 54 , OBJECTIVES : About 35 % of humans have methane-producing gut flora . Methane-producing irritable bowel syndrome ( IBS ) subjects are generally constipated . In animal models , methane infusion slows intestinal transit . Whether methanogenic flora alters colonic transit or stool characteristics and its relationship to constipation is unclear . The aim of this study was to examine the prevalence and association of methanogenic flora in patients with slow transit ( ST ) constipation and normal transit ( NT ) constipation and non-constipated controls . METHODS : Ninety-six consecutive subjects with chronic constipation ( CC ) ( Rome III ) were evaluated with radio-opaque marker ( ROM ) transit studies and were classified as ST ( > 20 % ROM retention ) or NT . All constipated subjects and 106 non-constipated controls underwent breath tests to assess methane production . Baseline CH4 of ≥3 p.p.m . was used to define presence of methanogenic flora . Stool frequency and consistency were assessed using a prospect i ve stool diary . Correlation analyses were performed . RESULTS : Forty-eight subjects had ST and 48 had NT . Prevalence of methanogenic flora was higher ( P<0.05 ) in ST ( 75 % ) compared to NT ( 44 % ) or controls ( 28 % ) . ST patients had higher methane production compared to NT and controls ( P<0.05 ) . NT patients also produced more methane compared to controls ( P<0.05 ) . There was moderate(P<0.05 ) correlation among baseline , peak , and area under the curve ( AUC ) of methane response with colonic transit but not with stool characteristics . CONCLUSIONS : Presence of methanogenic flora is associated with CC . Methane production after carbohydrate challenge and its prevalence were higher in ST than NT , although stool characteristics were similar in both groups . Methane production correlated with colonic transit , suggesting an association with stool transport but not with stool characteristics The presence of methane on lactulose breath test among irritable bowel syndrome ( IBS ) subjects is highly associated with the constipation-predominant form . Therefore , we set out to determine whether methane gas can alter small intestinal motor function . In dogs , small intestinal fistulae were created to permit measurement of intestinal transit . Using a radiolabel , we evaluated transit during infusion of room air and subsequently methane . In this model , small intestinal infusion of methane produced a slowing of transit in all dogs by an average of 59 % . In a second experiment , guinea pig ileum was pinned into an organ bath for the study of contractile activity in response to brush strokes applied to the mucosa . The force of contraction was measured both orad and aborad to the stimulus . The experiment was repeated while the bath was gassed with methane . Contractile activities orad and aborad to the stimulus were significantly augmented by methane compared with room air ( P < 0.05 ) . In a third experiment , humans with IBS who had undergone a small bowel motility study were compared such that subjects who produced methane on lactulose breath test were compared with those producing hydrogen . The motility index was significantly higher in methane-producing IBS patients ( 1,851 + /- 861 ) compared with hydrogen producers ( 1,199 + /- 301 ) ( P < 0.05 ) . Therefore , methane , a gaseous by-product of intestinal bacteria , slows small intestinal transit and appears to do so by augmenting small bowel contractile activity OBJECTIVE : We have recently found an association between abnormal lactulose breath test ( LBT ) findings and irritable bowel syndrome ( IBS ) . The current study was design ed to test the effect of antibiotic treatment for IBS in a double-blind fashion . METHODS : Consecutive IBS subjects underwent an LBT with the results blinded . All subjects were subsequently r and omized into two treatment groups ( neomycin or placebo ) . The prevalence of abnormal LBT was compared with a gender-matched control group . Seven days after completion of treatment , subjects returned for repeat LBT . A symptom question naire was administered on both days . RESULTS : After exclusion criteria were met , 111 IBS subjects ( 55 neomycin , 56 placebo ) entered the study , with 84 % having an abnormal LBT , compared with 20 % in healthy controls ( p < 0.01 ) . In an intention-to-treat analysis of all 111 subjects , neomycin result ed in a 35.0 % improvement in a composite score , compared with 11.4 % for placebo ( p < 0.05 ) . Additionally , patients reported a percent bowel normalization of 35.3 % after neomycin , compared with 13.9 % for placebo ( p < 0.001 ) . There was a grade d response to treatment , such that the best outcome was observed if neomycin was successful in normalizing the LBT ( 75 % improvement ) ( one-way ANOVA , p < 0.0001 ) . LBT gas production was associated with IBS subgroup , such that methane excretion was 100 % associated with constipation-predominant IBS . Methane excretors had a mean constipation severity of 4.1 , compared with 2.3 in all other subjects ( p < 0.001 ) . CONCLUSIONS : An abnormal LBT is common in subjects with IBS . Normalization of LBT with neomycin leads to a significant reduction in IBS symptoms . The type of gas seen on LBT is also associated with IBS subgroup OBJECTIVE : To study the epidemiology , symptom characteristics and impact of IBS in an urban Asian population . METHODS : A vali date d bowel symptom question naire was administered at face-to-face interviews to a r and om sample of 3,000 households in Singapore . RESULTS : The response rate was 78.2 % ( n = 2,276 , 1,143 males and 1,133 females ) . The age , sex , and racial distribution of our respondents were similar to the general population and there was no significant difference between respondents and nonrespondents by type of household . The prevalence of IBS was 11.0 % , 10.4 % , and 8.6 % by Manning ( > 1 criteria ) , Rome I and Rome II criteria , respectively . There was a higher prevalence of IBS in those < 50 years of age ( 9.7%vs 5.8 % 50 or > years , p = 0.002 ) , with more than 6 years of education ( 9.8%vs 5.9 % 6 year or < , p = 0.002 ) and living in l and ed property ( 16.8%vs 8.2 % living in apartments and public housing , p = 0.008 ) . There was no striking preponderance of female IBS subjects . Chronic constipation was a more common bowel disturbance than chronic diarrhea among our IBS subjects ( 51.0%vs 12.8 % ) . CONCLUSIONS : The prevalence and impact of IBS in our Asian urban society are greater than previously appreciated . We believe that our results provide a useful window to the future trends of gastrointestinal diseases for health and education authorities in developing Asian countries to look into BACKGROUND Previous studies in small series of healthy adults have suggested that parallel measurement of hydrogen and methane result ing from gut fermentation may improve the precision of quantitative estimates of carbohydrate malabsorption . Systematic , controlled studies of the role of simultaneous hydrogen and methane measurements using end-expiratory breath test techniques are not available . METHODS We studied seven healthy , adult methane and hydrogen producers and seven methane non-producers by means of end-expiratory breath test techniques . Breath gas concentrations and gastrointestinal symptoms were recorded at intervals for 12h after ingestion of 10 , 20 and 30 g lactulose . RESULTS In the seven methane producers the excretion pattern was highly variable ; the integrated methane responses were disproportional and not reliably reproducible . However , quantitative estimates of carbohydrate malabsorption on the basis of individual areas under the methane and hydrogen excretion curves ( AUCs ) tended to improve in methane producers after ingestion of 20 g lactulose by simple addition of AUCs of methane to the AUCs of the hydrogen curves . Estimates were no more precise in methane producers than similar estimates in non-producers . Gastrointestinal symptoms increased significantly with increasing lactulose dose ; correlation with total hydrogen and methane excretion was weak . CONCLUSIONS Our study suggests that in methane producers , simple addition of methane and hydrogen excretion improves the precision of semiquantitative measurements of carbohydrate malabsorption . The status of methane production should , therefore , be known to interpret breath tests semiquantitatively . The weak correlation between hydrogen and methane excretion and gas-related abdominal complaints suggests that other factors than net production of these gases may be responsible for the symptoms Two groups of beneficial bacteria are dominant in the human gut , the Bacteroidetes and the Firmicutes . Here we show that the relative proportion of Bacteroidetes is decreased in obese people by comparison with lean people , and that this proportion increases with weight loss on two types of low-calorie diet . Our findings indicate that obesity has a microbial component , which might have potential therapeutic implication |
706 | 25,935,732 | A significantly higher incidence of caries in abutment teeth was observed for densely sintered zirconia FDPs compared to metal-ceramic FDPs .
Survival rates of all types of all-ceramic FDPs were lower than those reported for metal-ceramic FDPs .
The incidence of framework fractures was significantly higher for reinforced glass ceramic FDPs and infiltrated glass ceramic FDPs , and the incidence for ceramic fractures and loss of retention was significantly higher for densely sintered zirconia FDPs compared to metal-ceramic FDPs | OBJECTIVE To assess the 5-year survival of metal-ceramic and all-ceramic tooth-supported fixed dental prostheses ( FDPs ) and to describe the incidence of biological , technical and esthetic complications . | PURPOSE The purpose of this study was to evaluate the long-term outcome of In-Ceram Alumina fixed partial dentures ( FPD ) performed in a general dental practice from 1992 to 1996 . MATERIAL S AND METHODS The study was conducted as a retrospective assessment of up to 9 years of patient records and a clinical follow-up examination of patients treated with In-Ceram Alumina FPDs . In 37 patients , 42 FPDs had been inserted during the selected period . After r and omized selection , 16 patients with 18 FPDs were examined clinical ly . The most common restorations comprised two and three units . Cantilever extensions were present on 64 % of the FPDs . Sixty-two percent of the FPDs extended into the posterior region . RESULTS The mean time in function for the 42 FPDs was 76 months ( range 2 to 110 months ) , with 86 % being followed for > 5 years . No adverse effects to either periodontal or pulpal tissues were recorded . The technical quality was very good , and patient satisfaction very high . Five FPDs fractured during the observation period , result ing in a total failure rate of 12 % . Two of these FPDs fractured as a consequence of external trauma . Excluding these , the total survival rate during the observation period was 93 % . Cumulative survival rate according to life table analysis was 93 % after 5 years and 83 % after 10 years . CONCLUSION The results suggest that the In-Ceram Alumina short-span FPD is a viable prosthetic alternative PURPOSE The aim of this prospect i ve study was to evaluate the clinical efficacy and long-term survival rate of three-unit fixed partial dentures ( FPDs ) made from lithium disilicate-based core ceramic . MATERIAL S AND METHODS Twenty-one three-unit FPDs were placed in 19 patients to replace single lost teeth in the esthetic area , following a study protocol that took clinical , esthetic , and radiologic aspects into consideration . Each case was review ed at 1 week following placement , at 6 months , and then annually for 10 years . Statistical analysis was performed using Kaplan-Meier survival analysis . RESULTS Out of the 19 patients , 14.3 % presented reversible postoperative sensitivity . Recession was observed in 24 % of dental posts , and 7.1 % presented marginal discoloration . Treatment did not increase either Bleeding or Plaque Index scores at prepared teeth ; secondary caries did not appear either . The restorations ' survival rate at the 10-year follow-up was 71.4 % ; six FPDs had fractured and one debonded . CONCLUSIONS Fracture failure rate was 28.6 % after 10 years ; a high percentage corresponded to connector fractures and occurred during the first 5 years . Lithium disilicate glass-ceramic FPDs present a higher risk of fracture than st and ard therapies ( metal-ceramic ) or other more recently developed ceramic material s. The prognosis for survival improves for Class I occlusion and nonparafunctional patients STATEMENT OF PROBLEM Although the favorable mechanical properties of zirconium oxide-based ceramics have increased the acceptance of fixed dental prostheses for use in the posterior regions of the mouth in recent years , there are few clinical studies documenting the longevity of these restorations . Furthermore , certain complications must be resolved before the material is used more extensively . PURPOSE The purpose of this r and omized prospect i ve study was to evaluate the clinical performance of zirconia ( Lava ) 3-unit posterior fixed dental prostheses . MATERIAL AND METHODS Twenty 3-unit fixed dental prostheses were placed in 17 participants to replace a second premolar or a first molar . Eleven were placed in the maxilla and 9 in the m and ible . All abutment teeth were prepared with a chamfer finish line of 0.8 to 1 mm , and frameworks were prepared with the Lava system . Restorations were cemented with a resin cement . Two calibrated examiners independently evaluated the fixed dental prostheses 1 week ( baseline ) and 1 , 2 , and 3 years after placement with the California Dental Association quality evaluation system . The periodontal parameters : the gingival index , plaque index , margin index , and the probing depths of abutment teeth and contralateral teeth were assessed . Data were analyzed by using descriptive statistics and the Wilcoxon signed-rank test ( α=.05 ) . RESULTS All fixed dental prostheses were rated satisfactory after 3 years , and no fracture of the framework was observed during the observation period . One fixed dental prostheses was lost because of a biological complication at the 3-year examination , and a small degree of chipping of the veneering ceramic was observed in 2 participants . No significant differences among the periodontal parameters of the test and control teeth were observed except for the margin index . CONCLUSIONS The results of a 3-year evaluation suggest that posterior zirconia 3-unit fixed dental prostheses are a reliable treatment This study aim ed to evaluate three- and four-unit posterior fixed partial dentures ( FPDs ) with zirconia frameworks after 5 years of function . Of the initial 30 subjects , 25 patients with 25 FPDs were examined after a mean follow-up period of 62.1 months . Five patients were not available for recall visits . Two FPDs failed before the 60-month evaluation because of framework fracture or delamination of the veneering ceramic after endodontic treatment . The 5-year survival rate was 92 % . Based on these results , it can be suggested that zirconia frameworks have sufficient mechanical requirements for use in the stress-bearing posterior region . Major fracture of the ceramic veneer could be related to inadequate framework design or bruxism The aim of this r and omized controlled trial was to evaluate the clinical performance of lithium disilicate fixed partial dentures ( FPDs ) . Eighteen patients received lithium disilicate FPDs ( study group ) , and 19 patients received porcelain-fused-to-metal FPDs ( control ) . After 6 years , the survival probabilities were found to be 63 % in the study group and 95 % in the control group ( log-rank test , P = .028 ) . The data suggest that strict conditions should be considered before the use of lithium disilicate glass-ceramic for FPDs OBJECTIVES The purpose of this prospect i ve study was to evaluate the clinical outcome of crown-retained fixed dental prostheses ( FDPs ) made from a lithium-disilicate glass-ceramic ( IPS e.max Press , Ivoclar-Vivadent ) . METHODS Thirty-six three-unit FDPs were placed in 28 patients . The FDPs replaced teeth in the anterior ( 16 % ) and posterior ( 84 % ) regions . All teeth were prepared following a st and ardized protocol . The size of the proximal connector of the FDPs was 12 mm2 ( anterior ) or 16 mm2 ( posterior ) . FDPs were cemented either with glass-ionomer cement ( n=19 ) or composite resin ( n=17 ) . The following parameters were evaluated at baseline , 6 months after cementation and then annually ( at abutment and contralateral teeth ) : probing pocket depth , plaque index , bleeding on probing , and tooth vitality . RESULTS Three FDPs were defined as drop-out . The mean observation period of the remaining 33 FDPs was 86 months ( range : 67 - 98 months ) : two FDPs in two patients had to be replaced ( 6 % ) because of fractures . The 8-year survival rate according to Kaplan-Meier was 93 % . In addition , chipping of the veneering material was found in two FDPs ( 6 % ) . Two abutments ( 3 % ) of two restorations had to be treated endodontically ; and two FDPs ( 6 % ) lost retention and had to be recemented . These complications did not affect the function of the involved restorations clinical ly . There were no significant differences between the periodontal parameters of the test and control teeth . SIGNIFICANCE Short-span crown-retained three-unit FDPs made from lithium-disilicate glass-ceramic can be used clinical ly irrespective of an adhesive or conventional cementation PURPOSE The aim of this prospect i ve clinical cohort study was to determine the success rate of 3- to 5-unit zirconia frameworks for posterior fixed partial dentures ( FPDs ) after 5 years of clinical observation . MATERIAL S AND METHODS Forty-five patients who needed at least 1 FPD to replace 1 to 3 posterior teeth were included in the study . Fifty-seven 3- to 5-unit FPDs with zirconia frameworks were cemented with 1 of 2 resin cements ( Variolink or Panavia TC ) . The following parameters were evaluated at baseline , after 6 months , and 1 to 5 years after cementation at test ( abutments ) and control ( contralateral ) teeth : probing pocket depth , probing attachment level , Plaque Index , bleeding on probing , and tooth vitality . Intraoral radiographs of the FPDs were taken . Statistical analysis was performed using descriptive statistics , Kaplan-Meier survival analysis , and the McNemar test . RESULTS Twenty-seven patients with 33 zirconia FPDs were examined after a mean observation period of 53.4 + /- 13 months . Eleven patients with 17 FPDs were lost to follow-up . After the 3-year recall visit , 7 FPDs in 7 patients were replaced because they were not clinical ly acceptable due to biologic or technical complications . After 5 years of clinical observation , 12 FPDs in 12 patients had to be replaced . One 5-unit FPD fractured as a result of trauma after 38 months . The success rate of the zirconia frameworks was 97.8 % ; however , the survival rate was 73.9 % due to other complications . Secondary caries was found in 21.7 % of the FPDs , and chipping of the veneering ceramic in 15.2 % . There were no significant differences between the periodontal parameters of the test and control teeth . CONCLUSIONS Zirconia offers sufficient stability as a framework material for 3- and 4-unit posterior FPDs . The fit of the frameworks and veneering ceramics , however , should be improved OBJECTIVE The aim of this prospect i ve clinical study was to evaluate the survival rates of IPS Empress 2 ( Ivoclar Vivadent ) all-ceramic crowns and fixed partial dentures ( FPDs ) after an observation period of up to 5 years . METHOD AND MATERIAL S Forty-three patients ( 19 women and 24 men ) were included in this study . The patients were treated with a total of 58 adhesive bonded IPS Empress 2 restorations . A total of 27 single crowns were placed on molars and premolars , and 31 three-unit FPDs were placed in the anterior and premolar regions . Clinical follow-up examinations took place at 6 , 12 , 24 , 36 , 48 , and 60 months after insertion . Statistical analysis of the data was calculated using the Kaplan-Meier method . RESULTS Results of the 50-month analysis ( interquartile range , 33 to 61 months ) showed that the survival rate was 100 % for crowns and 70 % for FPDs . Six failures that occurred exclusively in the three-unit FPDs were observed . Framework fractures were recorded in three FPD units where the connector dimensions did not meet the manufacturer specifications . Only one FPD exhibited an irreparable partial veneer fracture , and 2 FPDs showed evidence of biologic failures . The accuracy of fit and esthetic parameters were clinical ly satisfactory for crowns and FPDs . CONCLUSION The results of this 5-year clinical evaluation suggest that IPS Empress 2 ceramic is an appropriate material for the fabrication of single crowns . Because of the reduced survival rates , strict conditions should be considered before the use of IPS Empress 2 material for the fabrication of three-unit FPDs PURPOSE The aim of this prospect i ve study was to evaluate the clinical performance of zirconia-based posterior four-unit fixed dental prostheses ( FDPs ) after 4 years of clinical observation . MATERIAL S AND METHODS Between 2006 and 2010 , 10 patients ( 5 women , 5 men ; mean age : 52.8 years ) received 17 posterior four-unit FDPs . Two calibrated examiners evaluated the FDPs independently 1 week ( baseline ) , 6 months , and 1 , 2 , 3 , and 4 years after placement using California Dental Association ( CDA ) criteria . Periodontal status was assessed on both the abutment and contralateral control teeth using Plaque Index , Gingival Index , probing attachment level , and Margin Index parameters . Statistical analysis was performed using descriptive statistics and the Wilcoxon signed-rank test . RESULTS Three restorations were lost because of fractures at their distal connectors after a mean clinical service of 25.3 months , and one abutment tooth was extracted because of vertical root fracture 23 months after cementation . Three FDPs presented chipping of a moderate size 1 week before framework fracture , and minor chipping was observed in 2 other FDPs 1 week and 36 months after cementation . After 4 years of clinical service , the cumulative survival rate of the posterior four-unit FDPs was 76.5 % . No caries lesions were detected on the abutment teeth . The remaining restorations were judged to be satisfactory according to the CDA criteria . Periodontal parameters did not show significant differences between test and control teeth , but Gingival Index scores demonstrated a slight increase in inflammation in the distal abutments after 4 years ( P = .016 ) . CONCLUSIONS The use of zirconia-based posterior four-unit FDPs should be restricted for patients with high esthetic dem and s , except in patients where at least 4 mm of height is available for connector thickness The objective of this prospect i ve clinical study was to calculate the survival rate of IPS-Empress2 crowns and fixed partial dentures ( FPD ) over a three-year period . In 43 patients 27 IPS-Empress2 crowns and 31 fixed partial dentures were adhesively luted . Crowns were placed on premolars and molars and FPDs were inserted in the anterior and premolar area . Abutments were prepared with a circular 1.2 mm wide shoulder . The clinical follow-up examination took place after 6 , 12 , 24 , 36 and 48 months . After a mean of 38 months , the survival rate ( Kaplan-Meier ) of all-ceramic crowns was 100 % and of the three unit FDP 72.4 % . There were a total of six complete failures which occurred only with the three-unit IPS-Empress2 FPDs . Three FPDs exhibited fractures of the framework for which the manufacturer 's instructions of connector-dimension was not satisfied , and one FPD exhibited an irreparable incomplete veneer fracture . Further two FPDs showed biological failures . The accuracy of fit and esthetics were clinical ly satisfactory . The three-year results showed the IPS-Empress2-ceramic as an adequate all-ceramic material for single crowns . The use for FPD needs further critical consideration BACKGROUND The authors conducted a prospect i ve study to evaluate the long-term outcome of crown-retained fixed dental prostheses ( FDPs ) made from monolithic lithium disilicate ceramic ( IPS e.max Press , Ivoclar Vivadent , Schaan , Liechtenstein ) . METHODS Faculty dentists at the Department of Prosthodontics , Propaedeutics and Dental Material s , School of Dentistry , Christian-Albrechts University at Kiel , Germany , placed 36 three-unit FDPs in 28 patients to replace six anterior and 30 posterior teeth . The proximal connector size ( height and width ) was 4 × 3 millimeters for anterior FDPs and 4 × 4 mm for posterior FDPs . FDPs were cemented either conventionally with glass ionomer cement ( n = 19 ) or adhesively with resin-based composite ( n = 17 ) . Patients made annual recall visits . RESULTS The mean ( st and ard deviation ) observation period was 121 ( 12.8 ) months . FDPs ' survival rate ( survival being defined as remaining in place either with or without complications ) was 100 percent after five years and 87.9 percent after 10 years , and their success rate ( success being defined as remaining unchanged and free of complications ) was 91.1 percent after five years and 69.8 percent after 10 years . The cementation method did not affect the outcome . CONCLUSION Three-unit FDPs made from monolithic lithium disilicate ceramic showed five- and 10-year survival and success rates that were similar to those of conventional metal-ceramic FDPs . CLINICAL IMPLICATION S If the manufacturer 's recommendations are followed , three-unit FDPs made from monolithic lithium disilicate ceramic may be a safe alternative to metal-ceramic FDPs regardless of the cementation method used OBJECTIVES The aim of this prospect i ve clinical study was to assess the long-term clinical survival rate and the technical and biological complication rates of zirconia-based posterior FDPs . MATERIAL S AND METHODS Forty-five patients in need of one or more posterior FDPs received 57 three- to five-unit zirconia-based FDPs . The frameworks were fabricated by means of a prototype computer-aided manufacturing ( CAM ) system ( direct ceramic machining , DCM ) , first processing zirconia in the white stage . The frameworks were veneered with a prototype veneering ceramic . The FDPs were adhesively placed . At baseline , 6 months , and 1,2 , 3 , 5 , 8 and 10 years of function , the FDPs were examined for technical and /or biological complications . Furthermore , the periodontal health of the abutment teeth ( test ) and untreated control teeth was analyzed . Statistical analysis was performed applying descriptive statistics , Kaplan-Meier survival and multiple mixed effects regression tests . RESULTS Twenty-one patients with 26 FDPs were examined at a mean observation time of 10.7 + /- 1.3 years . A total of 16 FDPs were lost to follow-up . Fifteen FDPs had to be replaced due to technical/biological complications ; hence , the 10-year survival rate of the FDPs was 67 % . Three framework fractures occurred , result ing in a 10-year survival rate for the zirconia frameworks of 91.5 % . Chipping/fracture of the veneering ceramic was detected in 16 FDPs over 10 years ( complication rate 32 % ) . A significant correlation of the span of the FDPs and the incidence of chipping was observed : 4- and 5-unit FDPs had a 4.9 times higher probability for chipping than 3-unit FDPs . Marginal discrepancy/degradation was found in 90.7 % of the FDPs over 10 years . At 11 of the FDPs ( complication rate 27 % ) , secondary caries occurred . No difference of the periodontal health was found around test and control teeth . CONCLUSION The zirconia frameworks exhibited very good long-term stability . However , the zirconia-based FDPs frequently exhibited problems such as marginal deficiency or chipping of the veneering ceramic . Both problems may be associated with the prototype status of the system PURPOSE The purpose of this preliminary prospect i ve study was to evaluate the clinical outcome of crown-retained and inlay-retained fixed partial dentures ( FPDs ) made from a new lithium-disilicate glass-ceramic ( IPS e.max Press , Ivoclar Vivadent ) . MATERIAL S AND METHODS Eighty-one 3-unit FPDs were placed in 68 patients . The FPDs replaced teeth in the anterior ( 8 % ) and posterior region ( 92 % ) . All teeth were prepared according to a st and ardized protocol . The size of the proximal connector of the FPDs was 12 mm2 ( anterior ) or 16 mm2 ( posterior ) , respectively . Crown-retained FPDs were cemented either with glass ionomer ( n = 20 ) or resin composite ( n = 16 ) , while all inlay-retained FPDs ( n = 45 ) were cemented with resin composite . Initial follow-up was performed at 6 and 12 months and annually thereafter . RESULTS The mean observation periods were 48 months ( for crown-retained FPDs ) and 37 months ( for inlay-retained FPDs ) . None of the crown-retained FPDs failed during the observation period , while 6 inlay-retained FPDs ( 13 % ) had to be replaced . Six cases failed because of debonding ( n = 3 ) or a combination of debonding and fracture ( n = 3 ) . During the observation period , 2 patients died and the status of another 5 patients is unknown . The 4-year survival rate according to Kaplan-Meier was 100 % for crown-retained FPDs and 89 % for inlay-retained FPDs . The differences between the groups were statistically significant . CONCLUSION Crown-retained 3-unit FPDs made from a new glass-ceramic have a significantly better outcome up to 5 years than inlay-retained 3-unit FPDs over the observation period |
707 | 19,736,367 | Conclusion There is no evidence of an increased risk of treatment failure with short course of antibiotics for acute otitis media .
Among the short-course regimens , azithromycin use was associated with a lower risk of treatment failure while short-acting oral antibiotics and parenteral ceftriaxone may be associated with a higher risk of treatment failure | Objective To determine the efficacy of a short course of antibiotics ( < 4 days ) in comparison to a longer course ( ≥4 days ) for the treatment of acute otitis media in children . | A r and omized , open clinical trial was performed to compare azithromycin and amoxycillin/clavulanate potassium in children with acute otitis media with effusion . Patients were allocated to therapy with azithromycin ( 10 mg/kg once daily for 3 days ) or amoxycillin/clavulanate potassium ( 40 mg/kg/day divided into three equal doses for 10 days ) . Clinical examination and tympanometric evaluation were performed at baseline , and at day 3 to 5 , day 10 to 14 , day 28 to 30 and day 55 to 60 after the initiation of therapy . Tympanocentesis fluid cultures were collected at enrolment , and urine and blood sample s were obtained at baseline and at day 10 to 11 . Of 100 patients enrolled , 92 were considered evaluable . Middle ear cultures were positive in 53.2 % of the patients ; the most common pathogens were Streptococcus pneumoniae ( 33 % ) and Haemophilus influenzae ( 33 % ) . The response was satisfactory in 47 ( 100 % ) patients treated with azithromycin and 42 ( 95.4 % ) patients receiving A/C. Rates of persistence of middle ear effusion were comparable . Nausea and loose stools were more common in children treated with amoxycillin/clavulanate potassium ( P < or = 0.02 ) . Based on the comparable efficacy noted in this study , the lower incidence of side-effects and the convenience of a shorter duration of treatment , azithromycin represents an attractive therapeutic alternative to amoxycillin/clavulanate potassium and should be further evaluated in larger-scale clinical trials including patients with penicillin-resistant organisms A double-blind controlled trial of cefroxadine ( CXD ) 250 mg t.i.d . was undertaken to objective ly evaluate its safety and effectiveness in the treatment of acute suppurative otitis media and acute exacerbation of chronic suppurative otitis media , using cephalexin ( CEX ) 250 mg q.i.d . as a control drug , and the following results were obtained . In the treatment of acute suppurative otitis media , the 2 drugs produced almost equal outcomes , showing no significant difference in assessment s of both overall effects and usefulness . In the treatment of acute exacerbation of chronic suppurative otitis media , the 2 drugs exhibited no significant difference as well in overall effects by Wilcoxon 's two- sample test . However , the CEX group had significantly more nonresponsive patients , i.e. 35.5 % as compared with 9.7 % of the CXD group ( chi 2-test , P less than 0.05 ) . In the assessment of clinical usefulness as well , no significant difference was observed between the 2 groups . In the assessment of overall effects based on the patients whose isolated organisms were sensitive to the drugs , CEX group had more patients not responding to the treatment of acute exacerbation of chronic suppurative otitis media ( chi 2-test , P less than 0.05 ) . Bacteriological effects were not significantly different between the 2 drugs in both acute suppurative otitis media and acute exacerbation of chronic suppurative otitis media . Overall safety rating was not significantly different between the 2 drugs . Side effects occurred as the symptoms of digestive organ in 2 patients each in both groups ( equally an incidence of 2.6 % ) . As for the improvement of each symptom after treatment ( assessed on day 3 ) , CXD was superior in the improvement rate of otorrhea volume as the main symptom of acute exacerbation of chronic suppurative otitis media , while CEX was superior in that of otoobstruction feeling . From the above findings , it is presumed that CXD is a safe drug which can exhibit equal or superior therapeutic effects to CEX in the treatment of acute suppurative otitis media and acute exacerbation of chronic suppurative otitis media , at 3/4 of the CEX dose level An open multicentre study was conducted in 484 children between the ages of 6 months and 12 years with otitis media to compare the efficacy , the safety and the tolerance of once-daily azithromycin given for three days versus thrice-daily amoxicillin/clavulanic acid ( CA ) given for ten days . A satisfactory response ( cure plus improvement ) was noted 10 to 14 days after the start of treatment in 199 of 215 ( 92.6 % ) azithromycin-treated children and in 186 of 198 ( 93.9 % ) amoxicillin/CA-treated children . The relationship between treatment and clinical response was independent of chronicity of infection and the presence or absence of a perforated eardrum . Improvement in signs and symptoms of otitis media occurred significantly more rapidly in the children treated with azithromycin . Treatment-related or possibly treatment-related adverse events were recorded in 11 of 243 ( 4.5 % ) azithromycin-treated patients and in 20 of 240 ( 8.3 % ) treated with amoxicillin/CA . No patients in the azithromycin treatment group were withdrawn from treatment , but six amoxicillin/CA patients , including two < 2 years of age , discontinued treatment prematurely because of adverse events ; the difference between treatment groups was statistically significant ( p=0.0146 ) . It is concluded that azithromycin given as an oral suspension once daily for three days is as safe and effective as amoxicillin/CA given thrice daily for ten days in the treatment of children with otitis media ABSTRACT Infants and young children , especially those in day care , are at risk for recurrent or persistent acute otitis media ( AOM ) . There are no data on oral alternatives to high-dose amoxicillin-clavulanate for treating AOM in these high-risk patients . In this double-blind , double-dummy multicenter clinical trial , we compared a novel , high-dose azithromycin regimen with high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent AOM . Three hundred four children were r and omized ; 300 received either high-dose azithromycin ( 20 mg/kg of body weight once a day for 3 days ) or high-dose amoxicillin-clavulanate ( 90 mg/kg divided twice a day for 10 days ) . Tympanocentesis was performed at baseline ; clinical response was assessed at day 12 to 16 and day 28 to 32 . Two-thirds of patients were aged ≤2 years . A history of recurrent , persistent , or recurrent plus persistent AOM was noted in 67 , 18 , and 14 % of patients , respectively . Pathogens were isolated from 163 of 296 intent-to-treat patients ( 55 % ) . At day 12 to 16 , clinical success rates for azithromycin and amoxicillin-clavulanate were comparable for all patients ( 86 versus 84 % , respectively ) and for children aged ≤2 years ( 85 versus 79 % , respectively ) . At day 28 to 32 , clinical success rates for azithromycin were superior to those for amoxicillin-clavulanate for all patients ( 72 versus 61 % , respectively ; P = 0.047 ) and for those aged ≤2 years ( 68 versus 51 % , respectively ; P = 0.017 ) . Per-pathogen clinical efficacy against Streptococcus pneumoniae and Haemophilus influenzae was comparable between the two regimens . The rates of treatment-related adverse events for azithromycin and amoxicillin-clavulanate were 32 and 42 % , respectively ( P = 0.095 ) . Corresponding compliance rates were 99 and 93 % , respectively ( P = 0.018 ) . These data demonstrate the efficacy and safety of high-dose azithromycin for treating recurrent or persistent AOM In r and omized , double-blind trials of antibiotic therapy for acute otitis media that determined both clinical and bacteriologic outcomes , clinical success rates were ( 93 % ) 236 of 253 for patients with bacteriologic success , ( 62 % ) 25 of 40 for those with bacteriologic failure , and ( 80 % ) 124 of 155 for those with nonbacterial acute otitis media . These rates were used to calculate the effectiveness of three strategies for assessing drug efficacy : ( 1 ) tympanocentesis and culture before and during therapy ( bacteriologic efficacy ) , ( 2 ) tympanocentesis before therapy and assessment of clinical efficacy in bacterial acute otitis media , and ( 3 ) no tympanocentesis and assessment of clinical efficacy in clinical ( total ) acute otitis media . For a drug with a bacteriologic efficacy of 100 % , calculated clinical efficacy was 93 % for bacterial acute otitis media and 89 % for clinical acute otitis media . For a drug with bacteriologic efficacy of 27 % , a rate consistent with no antibacterial therapy , efficacy was 71 % for bacterial acute otitis media and 74 % for clinical acute otitis media . We conclude that if efficacy is measured by symptomatic response , drugs with excellent antibacterial activity will appear less efficacious than they really are and drugs with poor antibacterial activity will appear more efficacious than they really are . The predominant phenomenon is that drugs with poor antibacterial activity will appear to be clinical ly effective in the treatment of acute otitis media Abstract Objective To assess the efficacy of three days versus five days of treatment with oral amoxicillin for curing non-severe pneumonia in children . Design R and omised , double blind , placebo controlled multicentre trial . Setting Outpatient departments of seven referral hospitals in India . Participants 2188 children aged 2 - 59 months , 1095 given three days of treatment and 1093 given five days . Intervention Oral amoxicillin 31 - 54 mg/kg/day in three divided doses . Main outcome measures Treatment failure : defined as development of chest indrawing , convulsions , drowsiness , or inability to drink at any time ; respiratory rate above age specific cut points on day 3 or later ; or oxygen saturation by pulse oximetry < 90 % on day 3 . Results The clinical cure rates with three days and five days of treatment were 89.5 % and 89.9 % , respectively ( absolute difference 0.4 ( 95 % confidence interval - 2.1 to 3.0 ) ) . Adherence to treatment regimen was 94 % and 85 % for three day and five day treatments , respectively . Loss to follow up was 5.4 % by day 5 . There were no deaths , 41 hospitalisations , and 36 minor adverse reactions . There were 225 ( 10.3 % ) clinical failures and 106 ( 5.3 % ) relapses , and rates were similar in both treatments . At enrolment , 513 ( 23.4 % ) children tested positive for respiratory syncytial virus , and Streptococcus pneumoniae and Haemophilus influenzae were isolated from the nasopharynx in 878 ( 40.4 % ) and 496 ( 22.8 % ) children , respectively . Clinical failure was associated with isolation of respiratory syncytial virus ( adjusted odds ratio 1.95 ( 95 % confidence interval 1.0 to 3.8 ) ) , excess respiratory rate of > 10 breaths/minute ( 2.89 ( 1.83 to 4.55 ) ) , and non-adherence with treatment at day 5 ( 11.57 ( 7.4 to 18.0 ) ) . Conclusions Treatment with oral amoxicillin for three days was as effective as for five days in children with non-severe pneumonia Abstract Two hundred and fifteen children aged 4 months–6 years with acute otitis media ( AOM ) were r and omized to be treated either by a single i.m . injection of ceftriaxone , 50 mg/kg , with a second dose in the event of unsatisfactory response after 48 h or a history of recurrent AOM ( 109 patients ) or amoxicillin clavulanate 12.5 mg tid ( 106 patients ) . The failure rate was similar in children treated by ceftriaxone and amoxicillin clavulanate , 4.6 % and 4.7 % , respectively ( st and ard error for intergroup difference −2.87 % , 95 % confidence interval −5.62 % to 5.87 % ) . No significant differences between the groups were found in the dynamics of the resolution of the acute symptomatology , otoscopy findings , relapse rate at 30 days or tympanographic evidence of middle ear effusion at the scheduled visits on days 30 , 60 and 90 . Recurrence of AOM between days 31 and 90 was observed significantly in more children treated with amoxicillin clavulanate than with ceftriaxone – 25 out of 84 ( 29.4 % ) versus 11 out of 81 ( 13.6 % ) ( P=0.012 ) . Conclusion Ceftriaxone injection(s ) is as efficient at least as 10-day oral amoxicillin clavulanate for treatment of acute otitis media in children . Although not recommended as routine , ceftriaxone can be considered in the management of acute otitis media under special circumstances , particularly in cases when the ability to tolerate or absorb oral drugs is compromised , in children refusing or unable to take oral therapy or when the compliance is question able 103 children between 1 and 10 years of age participated in a double-blind placebo-controlled trial testing the effect of penicillin-V , 55 mg/kg/day , for two days versus seven days in acute otitis media . No significant differences could be demonstrated with regard to earache , healing of the tympanic membrane , tympanometry , fever or common cold symptoms . 76 % in the group treated for seven days had a satisfactory course of the disease , compared to 71 % in the group treated for two days ( p greater than 0.1 ) . In spite of the relatively small number of patients , it is concluded that the effect of penicillin for additional five days in acute otitis media after the initial treatment for two days , can at most be marginal . The advantages of a shortened treatment period are several ; the authors have outlined a new treatment modality , consisting of masterful inactivity for 8 - 12 hours , penicillin-V for two days , and myringotomy in refractory cases , after a new evaluation by the otologist . We believe hereby to be able to reduce penicillin consumption in children with acute otitis media to about 15 % of the previous level , without increasing the risk of serious complications BACKGROUND Compared with 5 days of dosing , a 3 day dosing regimen of azithromycin for treatment of acute otitis media ( AOM ) may improve compliance , will simplify therapy for the caregiver and , by giving the same total dose as the 5 day regimen , provide more drug when the bacterial burden is highest . METHODS Children of 6 months-12 years were enrolled if they had had symptoms and signs of AOM for < 4 weeks and tympanic membrane effusion by acoustic reflectometry . Eligible children were r and omized to azithromycin 10 mg/kg/day x 3 days or co-amoxiclav 45 mg/kg/day x 10 days . The primary endpoint was clinical response at day 28 . RESULTS One hundred and eighty-eight children ( mean age 3.5 years ) were r and omized to azithromycin and 185 to co-amoxiclav . At day 10 , the clinical success rate was 153/185 ( 83 % ) in children treated with azithromycin and 159/181 ( 88 % ) in children treated with co-amoxiclav . At day 28 , 134/182 ( 74 % ) of the children were cured on azithromycin compared with 124/180 ( 69 % ) on co-amoxiclav . Also at day 28 , signs of AOM , such as abnormal reflectometry ( 45 % versus 59 % ; P = 0.017 ) , bulging of the eardrum ( 10 % versus 16 % ; P = 0.059 ) and loss of tympanic membrane l and marks ( 11 % versus 22 % ; P = 0.010 ) were seen less frequently in azithromycin- than co-amoxiclav-treated children , respectively . Adverse events related to therapy were seen in 11 % of azithromycin patients compared with 20 % on co-amoxiclav ( P = 0.014 ) . CONCLUSIONS Azithromycin given over 3 days is as effective as co-amoxiclav for treatment of AOM , may result in more complete resolution of tympanic membrane disease , and is better tolerated In order to evaluate the clinical efficacy and safety profiles of single-dose ceftriaxone ( 50 mg/kg , not exceeding 1 g ) and a 10-day course of amoxicillin-clavulanate ( amoxi-clav ) [ 45 mg/kg/day , in 3 divided doses ] in children with acute otitis media ( AOM ) , we conducted a prospect i ve , comparative , r and omized trial . Between February 2000 and April 2002 , 110 children with a mean age of 30.73 + /- 20.79 months were enrolled . 109 patients were evaluated for the safety assessment . The intent-to treat population included 96 patients who completed at least 3 days of treatment . The st and ard analysis population included 73 patients who completed the 10-day treatment period without any major violation . For the st and ard analysis population , 57 out of 73 patients experienced treatment success ; 31 out of 41 patients in the ceftriaxone group were cured compared with 25 out of 32 patients in the amoxi-clav group . The rate of persistence of middle-ear fluid did not differ between the 2 groups at day 11 or day 28 . A higher treatment preference rate was observed in the ceftriaxone group ( 93.9 % vs 58.6 % ) . The most common drug-related adverse effects were found in the digestive system , skin and appendages in both treatment groups . A single dose of ceftriaxone is as safe and effective as amoxi-clav for curing patients with acute otitis media . In addition , a substantially higher proportion of patients receiving single-dose ceftriaxone showed a preference for the study medication compared with those treated with amoxi-clav for 10 days In this open study , a three-day regimen of azithromycin ( single daily dose of 10 mg/kg ) was compared with a ten-day regimen of amoxycillin paediatric suspension ( 30 mg/kg/day in three divided doses ; children > 20 kg received 250 mg tid daily ) in 154 children ( aged 2 - 12 years ) with a clinical diagnosis of acute otitis media ( 13 recurrent ) . Full clinical , bacteriological and laboratory safety assessment s were performed during and after the study . Of the 77 azithromycin patients , 61 ( 79 % ) were considered cured , 15 ( 19 % ) improved and one ( 1 % ) failed , compared with 45 ( 58 % ) cured , 28 ( 36 % ) improved and four ( 5 % ) failed among the 77 amoxycillin patients . Excluding from analysis the 13 patients with recurrent otitis media , azithromycin was found to be significantly superior to amoxycillin ( P = 0.003 ) . The incidence of side-effects was low , with only two ( 3 % ) and three ( 4 % ) patients reporting adverse events with azithromycin and amoxycillin , respectively . These were gastrointestinal in nature and of mild or moderate severity , except for one case of severe diarrhoea in the amoxycillin group . No treatment-related abnormalities in the laboratory safety tests were observed , and no patients withdrew from therapy . A three-day regimen of azithromycin was therefore shown to be more effective than , and as well tolerated as , amoxycillin in the treatment of children with acute otitis media In an open-label study , the concentrations of azithromycin in middle ear effusions and plasma were determined in 29 children between 1 and 8 years of age with a diagnosis of either secretory otitis media of at least 1 month 's duration or acute otitis media . Azithromycin ( 10 mg/kg ) was administered as a single dose 12 , 24 or 48 h before the insertion of tympanostomy tubes to 17 children with secretory otitis media and once daily for 5 days ( 10 mg/kg on day 1 , 5 mg/kg on days 2 - 5 ) to 12 children with acute otitis media . In the 16 evaluable patients with secretory otitis media , azithromycin penetrated middle ear effusions , with group mean concentrations approximately two orders of magnitude greater than the concurrent plasma concentrations 12 , 24 and 48 h after administration . Similar plasma : effusion ratios were found 24 and 48 h after starting once-daily therapy in 10 evaluable patients with acute otitis media Azithromycin is a newly developed azalide antibiotic which is very active against microbes causing respiratory tract infections ; tissue concentrations remain elevated for a long time after discontinuation of treatment . A clinical study was conducted to compare azithromycin ( 10 mg/kg administered as a single daily dose for 3 days ) with amoxycillin/clavulanic acid ( 50 mg/kg/day given b.i.d . for 10 days ) in 30 children with otitis media . Sensitivity testing demonstrated good azithromycin activity against beta-haemolytic streptococci , Moraxella catarrhalis , Haemophilus influenzae and Staphylococcus aureus . By day 12 , clinical cure was recorded in 14/15 children treated with azithromycin and this was maintained at day 30 . In the day 12 and 13/15 children by day 30 . It was concluded that a 3-day azithromycin regimen produces a satisfactory clinical response and the eradication of key pathogens , and was acceptable for children OBJECTIVE To compare the efficacy and the safety of a single intramuscular dose of ceftriaxone , 50 mg/kg , vs. a 10-day course of amoxicillin/clavulanate ( amox/clav ) therapy , 80 mg/kg/day of amoxicillin : 10 mg/kg/day of clavulanate in three divided doses , in children with acute otitis media ( AOM ) and to evaluate the changes in nasopharyngeal flora after treatment . METHODS In a prospect i ve , comparative , open r and omized , multicenter trial , children were scheduled to return for visits on Days 12 to 14 ( main end point ) and Days 28 to 42 after the beginning of treatment for AOM . A nasopharyngeal swab for bacterial culture was obtained before the treatment and at Days 12 to 14 . RESULTS Between February , 1995 , and May , 1996 , 513 children with a mean age of 14.2 + /- 6.7 months were enrolled . All the patients were evaluable for the safety and intent-to-treat analyses and 463 for the per protocol efficacy . At Days 12 to 14 clinical success was obtained in 186 of the 235 children ( 79 % ) given ceftriaxone and in 188 of the 228 children ( 82.5 % ) treated with amox/clav . Among the patients with clinical success on Days 12 to 14 , the success was maintained at Days 28 to 42 for 108 of 183 ( 59 % ) patients in the ceftriaxone group and 103 of 187 ( 55 % ) patients in the amox/clav group . Before the antibiotic treatment the percentages of children carrying Streptococcus pneumoniae ( 59.1 % ) , Haemophilus influenzae ( 39.4 % ) , Moraxella catarrhalis ( 55.7 % ) and the rate of penicillin-resistant S. pneumoniae ( 52.2 % ) were comparable between the 2 groups . At Days 12 to 14 the carriage of S. pneumoniae and M. catarrhalis was significantly different between the patients treated with ceftriaxone , 43.9 and 42.2 , respectively , and the patients treated with amox/clav , 17.4 and 11.1 % , respectively . Among the children carrying S. pneumoniae at Days 12 to 14 , the percentage of penicillin-resistant strains reached 63.4 % in the ceftriaxone treatment group and 83.0 % in the amox/clav treatment group , ( P = 0.02 ) . Adverse events ( mainly diarrhea ) related to the study medication were reported more frequently ( P < 0.0001 ) in the amox/clav treatment group . CONCLUSIONS In an area with a high rate of penicillin-resistant S. pneumoniae , a single dose of ceftriaxone is as efficient as a 10-day course of amox/clav in the treatment of AOM in young children . There was for the two regimens an increased rate of penicillin-resistant strains among the pneumococci carried , whereas the chance for a child to carry a penicillin resistant S. pneumoniae did not increase after treatment This study evaluated the efficacy of a single dose of intramuscular ceftriaxone for acute otitis media in children , using amoxicillin as a control . ( There is currently no established single-dose treatment for this condition . ) In a prospect i ve , r and omized , double-blind , clinical trial , 233 children , aged 5 months to 5 years , with uncomplicated acute otitis media were r and omly assigned to receive either a single intramuscular injection of ceftriaxone ( 50 mg/kg ) plus placebo oral suspension for 10 days , or a placebo injection plus amoxicillin oral suspension ( 40 mg/kg per day divided three times per day ) for 10 days in a double-blind fashion . Demographic and clinical characteristics were similar in both groups . Treatment was successful in 107 of 117 given amoxicillin ( 91 % , 95 % confidence interval 86 % to 97 % ) and 105 of 116 given ceftriaxone ( 91 % , 95 % confidence interval 85 % to 96 % ) . Rates of improvement , failure , relapse , and reinfection were similar in both groups , as were the otoscopic and tympanometric evaluations at the 14- and 60-day follow-up visits . It is concluded that a single intramuscular injection of ceftriaxone ( 50 mg/kg ) is as effective as 10 days of oral amoxicillin for the treatment of uncomplicated acute otitis media in children The aim of the present study was to compare the efficacy and the tolerability of three different antibiotic regimens for the treatment of acute otitis media in paediatric patients . 75 children , age range 6 months-6 years , divided into three groups , were involved in the study , each group consisting of 25 r and omly assigned children ( Group 1 , amoxicillin 40 mg/kg tid per os for 10 days ; Group 2 , cefuroxime axetil 30 mg/kg bid per os for 10 days ; ceftriaxone 50 mg/kg single-dose i.m . ) . No statistically significant difference was noted in the clinical efficacy among the different groups . Although amoxicillin is the drug of choice in paediatric otitis media , single dose ceftriaxone might be considered as an interesting alternative regimen when ease of administration and cost of therapy are considered Fifty-two children ( mean age 23 months ) with acute otitis media were treated r and omly with either a single intramuscular dose of ceftriaxone ( Rocephin ) 50 mg/kg ( 27 patients ) or 7 days of amoxicillin 12.5 mg/kg t.i.d . ( 25 patients ) . The rate of resolution of acute symptoms and incidence of recurrences and relapses during the first months after commencement of the therapy was similar in the two groups . One week following the start of treatment no difference was observed in the proportion of patients with tympanometric evidence of middle ear effusion ( MEE ) in either of the two groups . On day 30 , however , significantly more patients from the ceftriaxone group had flat tympanograms-83 % as compared to 47 % in the amoxicillin group . Therefore , single-dose ceftriaxone therapy can not be suggested at present as routine therapy for acute otitis , although it may be considered a reasonable alternative in noncompliant patients OBJECTIVE To compare the efficacy and safety of a single ceftriaxone injection with 10-day oral amoxicillin in the treatment for children 's acute otitis media . METHODS This study was a prospect i ve , comparative , open r and omized , multicenter trial . In the ceftriaxone group , a single dose sodium ceftriaxone ( 50 mg/kg , total dose < 1 g ) was injected . In the amoxicillin group , the oral amoxicillin [ 40 mg/(kg.d ) , tid ] was used for 10 days . Totally 236 cases aged from 0.5 to 12 years were enrolled and 212 cases completed the study . These patients were followed up twice and clinical signs and symptoms were recorded , otoscopy , peripheral blood WBC count , hearing test ( pure tone test ) and tympanography were performed . RESULTS In the ceftriaxone group , 103/106 cases were cured or improved ( 97.17 % ) , while in the amoxicillin group 96/106 cases were cured or improved ( 90.57 % ) ( P < 0.05 ) . Ceftriaxone was significantly better than amoxicillin in the treatment . Totally 4 cases had side effects such as papular skin rash , urticaria around mouth , skin pigmentation , two cases in the ceftriaxone group and other two cases in the amoxicillin group . There was no significant difference between the 2 groups in side effects . CONCLUSION Ceftriaxone injection was significantly better than ten-day oral amoxicillin for treatment of acute otitis media in children . The single dose regimen with ceftriaxone seems to be a good choice for children , particularly for A prospect i ve study was carried out in 274 children aged 3 to 10 years with acute otitis media . They were r and omly allocated to one of two treatment regimens : ( a ) a seven day course of amoxycillin 125 mg three times a day , and ( b ) a two day course of amoxycillin 750 mg twice a day . They were followed up by symptom diaries and clinical examination . The findings in the 243 children who completed the trial showed that the short course of treatment was as effective as the seven day course in the speed of resolution of symptoms and signs , irrespective of previous history of otitis media or of episodes in which bulging of the eardrums was observed at presentation . A subgroup of 185 children was followed up for one year after entry to the trial . During this period no appreciable differences emerged between the two antibiotic regimens , either in recurrence rate of otitis media or in the frequency of hearing loss at one month and six months after entry to the study . Side effects of treatment were few , and those that could be attributed to antibiotic use occurred with equal frequency in the two treatment groups OBJECTIVE The purpose of this prospect i ve , r and omized , single-blind trial was to assess the clinical efficacy of a single intramuscular dose of ceftriaxone compared with 10 days of oral trimethoprim-sulfamethoxazole ( TMP-SMZ ) in treating acute otitis media ( AOM ) . METHODS Children aged 3 months through 3 years diagnosed with AOM ( signs of acute illness plus evidence of middle-ear effusion ) were r and omized to treatment with either a single intramuscular dose of ceftriaxone ( maximum dose of 50 mg/kg ) or 10 days of oral trimethoprim-sulfamethoxazole ( 8 mg of TMP and 40 mg of SMZ/kg/day in two divided doses ) . Children were evaluated at scheduled visits on days 3 , 14 , and 28 , and the parents were telephoned on day 5 . Children were assessed as cured , improved , or failed on day 3 , and as cured or failed on days 14 and 28 . Children ill at other times during the study period were , if possible , seen and assessed by the study team . RESULTS Of 596 children enrolled during the study period , 484 were evaluable . Characteristics of evaluable subjects did not differ significantly by drug . On day 3 , 223/241 children in the ceftriaxone group ( 92.5 % ) and 231/243 ( 95.1 % ) in the TMP-SMZ group were cured or improved . On day 14 , 158/197 ( 80.2 % ) in the ceftriaxone group and 174/212 ( 82.1 % ) in the TMP-SMZ group were cured . On day 28 , 108/136 ( 79.4 % ) in the ceftriaxone group and 124/155 ( 80 % ) in the TMP-SMZ group were cured . Persistence of middle-ear fluid did not differ between groups at day 14 ( 55 % in the ceftriaxone group vs 47 % in the TMP-SMZ group ; P = .16 ) or at day 28 ( 39 % vs 43 % ; P = .48 ) . Pain at the injection site persisting at day 3 occurred in 8.4 % of children receiving ceftriaxone . New diarrhea was more common in the ceftriaxone group ( 23.6 % vs 9.2 % ; P < .001 ) . CONCLUSION A single intramuscular dose of ceftriaxone is comparable in clinical efficacy to 10 days of oral TMP-SMZ for treatment of AOM The authors compared the efficacy , safety and tolerance of azithromycin and clarithromycin in pediatric patients with acute otitis media . A r and omized , open clinical trial was performed comparing azithromycin and clarithromycin in children aged 6 months to 12 years of age with acute otitis media with effusion . Patients were allocated to azithromycin at 10 mg/kg once daily for 3 days or to clarithromycin at 15 mg/kg day divided into two equal doses for 10 days . Clinical examinations and tympanometric evaluations were performed at baseline , day 3 - 5 , day 10 - 14 , day 28 - 30 and day 50 - 60 . Tympanocentesis fluid cultures were collected at enrollment and urine and blood sample s were obtained at baseline and day 10 - 14 . Of 100 patients enrolled , 97 were considered evaluable . The most common middle ear pathogens were Streptococcus pneumoniae ( 60 % ) , Haemophilus influenzae ( 15 % ) and Staphylococcus aureus ( 13 % ) . Fifty patients ( 100 % ) treated with azithromycin and 45 ( 95.7 % ) patients treated with clarithromycin had a satisfactory clinical response . Rates of persistence of middle ear effusion and possible drug related side effects were comparable . Based on the efficacy and safety results , azithromycin for 3 days and clarithromycin for 10 days are considered to represent an attractive alternative for the treatment of children with acute otitis media A r and omised double-blind controlled trial compared three-day and 10-day courses of amoxycillin ( 25 mg/kg daily ) in children with otitis media . Seventeen doctors from five centres admitted 84 children between the ages of 2 and 10 years . Symptoms and signs were measured on admission to the trial , on day 3 , and on day 15 . Mother 's observations were recorded daily for 10 days . Audiograms were performed at four and 12 weeks after the end of the trial . The treatment groups showed little difference in the speed of resolution of symptoms and signs , the numbers of primary treatment failures , or the frequency of recurrent ear infections . There were no complications in either group . Most children with otitis media can probably be successfully and safely treated with no more than a three-day course of amoxycillin providing their progress is review ed about the fifth or sixth day after treatment started . This policy could save over 1 million pounds annually in antibiotic costs In order to objective ly evaluate the efficacy and the safety of ceftriaxone ( CTRX ) using once daily administration of 1 g to cases of acute suppurative otitis media and acute exacerbation of chronic suppurative otitis media , a group comparison study by the envelope method was conducted using cefotiam ( CTM ) as the control drug ( 2 g twice daily ) . The results obtained are summarized as follows . 1 . Clinical efficacies evaluated by the committee were 71 % in the CTRX group and 86 % in the CTM group for acute suppurative otitis media , and 63 % and 60 % , respectively , for chronic suppurative otitis media . When all cases were considered both groups evidence d a clinical efficacy of 64 % , and no significant difference was observed between the 2 groups . 2 . Clinical efficacies evaluated by the physician in charge were 65 % in the CTRX group and 86 % in the CTM group for acute suppurative otitis media , and 72 % and 60 % , respectively , for chronic suppurative otitis media . When all cases were considered efficacies were , respectively , 70 % and 64 % , showing no significant difference between the 2 groups . 3 . Bacteriological efficacies were 88 % in the CTRX group and 86 % in the CTM group for acute suppurative otitis media , and 74 % and 62 % , respectively , for chronic suppurative otitis media . With all cases bacterial eradication rates were , respectively , 76 % and 67 % . Bacterial eradication rates were always higher for the CTRX group than for the CTM group , but the difference was not significant between the 2 groups . 4 . Against infections caused by Staphylococcus aureus alone , CTRX showed equal clinical and bacteriological efficacies to CTM . 5 . As side effects , dermatitis , vomiting , and malaise were observed in 5 cases ( 4 % ) of the CTRX group and 3 cases ( 3 % ) of the CTM group . As clinical testing abnormalities , elevations of GOT , GPT , and Al-P , and thrombocytopenia were noted only in 3 cases ( 5 % ) of the CTRX group . Furthermore , all of these abnormalities were temporary and of moderate degree or mild , thus the safety of either drug was considered high . 6 . Clinical utilities were 71 % in the CTRX group and 86 % in the CTM group for acute suppurative otitis media , and 72 % and 62 % , respectively , for chronic suppurative otitis media . When all cases were included , they were 72 % and 66 % , respectively , and there was no significant difference between the 2 groups . It is concluded from the above results that CTRX is a highly useful drug with once daily administration of 1 g in the treatment of suppurative otitis media A total of 389 children ( age 0.6 - 10.2 years ) with typical signs and symptoms of acute otitis media were r and omized ( 1:1 ) to treatment with either azithromycin or co-amoxiclav . The dosage schedule for azithromycin was 10 mg/kg/day , in a single daily dose , administered for three days . Co-amoxiclav was given at a dose of 13.3 mg/kg ( amoxycillin equivalent ) tid for ten days . Patients were evaluated 4 - 6 days and 12 - 16 days after the start of therapy . A satisfactory clinical response was reported for 93.2 % of the 192 evaluable azithromycin-treated patients ( 144 cured , 35 improved ) , and for 97.3 % of the 189 evaluable co-amoxiclav-treated patients ( 148 cured , 36 improved ) . Six ( 3.0 % ) relapses occurred in the azithromycin group , and four ( 2.1 % ) in the co-amoxiclav treatment group , respectively . Side-effects were recorded in a significantly fewer number of the azithromycin patients ( 23 of 197 ; 11.7 % ) compared with the co-amoxiclav patients ( 43 of 192 ; 22.4 % , P < 0.02 ) . Adverse events were mainly gastrointestinal in nature , with diarrhoea the most frequent complaint ( 32 cases with co-amoxiclav ; five with azithromycin ; P < 0.001 ) . One patient from each group discontinued therapy because of treatment-related adverse events . Laboratory analyses ( mainly haematological in nature ) showed abnormalities in six of 100 azithromycin patients and ten of 101 co-amoxiclav patients . It was concluded that three-day , single-dose azithromycin and ten-day tid co-amoxiclav therapy have comparable clinical efficacy in paediatric patients with acute otitis media ; however , there was a lower incidence of side effects in the azithromycin group Background : High dose amoxicillin is recommended for the initial treatment of children with acute otitis media ( AOM ) , particularly patients at risk for having drug-resistant Streptococcus pneumoniae . Single dose azithromycin ( 30 mg/kg ) is considered an alternative agent for the treatment of AOM . Objective : To compare the clinical efficacy and safety of single dose azithromycin with that of high dose amoxicillin among children with uncomplicated AOM . Methods : This was a double blind , double dummy , multinational , clinical trial in which children ( 6–30 months of age ) with AOM were r and omized to treatment with single dose azithromycin ( 30 mg/kg ) or high dose amoxicillin ( 90 mg/kg/d , in 2 divided doses ) for 10 days . Tympanocentesis was performed at baseline and clinical responses were assessed at days 12–14 ( end of therapy ) and at days 25–28 ( end of study ) . Results : The study enrolled 313 patients , and 83 % of the patients were ≤2 years of age . A total of 158 patients in the azithromycin group and 154 in the amoxicillin group were considered clinical modified intent-to-treat patients . A middle ear pathogen was detected for 212 patients ( 68 % ) . Haemophilus influenzae was the most common pathogen ( isolated for 96 patients ) , followed by S. pneumoniae ( 92 patients ) , Moraxella catarrhalis ( 23 patients ) and Streptococcus pyogenes ( 23 patients ) . β-Lactamase production was observed for 17 % of H. influenzae isolates and 100 % of M. catarrhalis isolates . Thirty-five ( 38 % ) S. pneumoniae isolates were penicillin-nonsusceptible and 24 ( 26 % ) isolates were macrolide-resistant . At the end of therapy , clinical success rates for azithromycin and amoxicillin were comparable for all patients ( 84 and 84 % , respectively ) and for children ≤2 years of age ( 82 and 82 % , respectively ) . At the end of therapy and end of study , clinical efficacies among all microbiologic modified intent-to-treat evaluable subjects were comparable for patients treated with azithromycin ( 80 % ) and patients treated with amoxicillin ( 83 % ) . The rates of treatment-related adverse events for azithromycin and amoxicillin were 20 % and 29 % , respectively ( P = 0.064 ) . Diarrhea was more common in the amoxicillin group than in the azithromycin group ( 17.5 and 8.2 % , respectively ) ( P = 0.017 ) . Compliance , defined as completion of ≥80 % of the study medication , was higher in the azithromycin group ( 100 % ) than in the amoxicillin group ( 90 % ) ( P = 0.001 ) . Conclusions : In this study , single dose azithromycin was as effective as high dose amoxicillin for the treatment of children with AOM , whereas rates of adverse events were lower and compliance improved with the simplified single dose regimen An open r and omized trial was conducted in 159 children ( aged 1 to 8 years ) with acute otitis media to compare the clinical efficacy of azithromycin ( n = 105 ) and co-amoxiclav ( n = 54 ) . Azithromycin ( 10 mg/kg/day ) was administered as a single dose for three days and co-amoxiclav was given tid for ten days at a dosage according to the manufacturer 's instructions for the country . Of 103 evaluable azithromycin patients on day 3 to 5 after the start of therapy , 31 ( 30 % ) were considered cured , 67 ( 65 % ) improved and five ( 5 % ) failed compared with eight ( 15 % ) cured , 45 ( 83 % ) improved and one ( 2 % ) failed among the 54 evaluable co-amoxiclav treated patients . There was a higher number of azithromycin patients with complete resolution of symptoms at this first visit ( P = 0.056 ) . By day 10 to 12 , clinical equivalence between the two treatment groups was observed with clinical cure in 86 ( 88 % ) , improvement in 11 ( 11 % ) and failure in one ( 1 % ) of the 98 azithromycin patients , and in the 54 patients treated with co-amoxiclav , clinical cure was observed in 45 ( 83 % ) , and improvement in nine ( 17 % ) patients . Both drugs were well tolerated and treatment related side-effects were reported in 8/105 ( 8 % ) azithromycin and 2/54 ( 4 % ) co-amoxiclav patients . In the azithromycin treatment group , these were predominantly mild to moderate gastrointestinal effects , whilst in the co-amoxiclav treatment group , both reports were of mild erythematous rash . One patient from each treatment group was withdrawn due to side-effects ( azithromycin -- diarrhoea and vomiting ; co-amoxiclav -- erythematous pruritic rash ) . ( ABSTRACT TRUNCATED AT 250 WORDS ABSTRACT A prospect i ve , open-label , r and omized study was conducted in order to determine the bacteriologic efficacies of cefaclor and azithromycin in acute otitis media ( AOM ) . Tympanocentesis was performed on entry into the study and 3 to 4 days after initiation of treatment . Bacteriologic failure after 3 to 4 days of treatment with both drugs occurred in a high proportion of culture-positive patients , especially in those in whom AOM was caused by Haemophilus influenzae(16 of 33 [ 53 % ] of those treated with azithromycin and 13 of 34 [ 52 % ] of those treated with cefaclor ) . Although a clear correlation of the persistence of the pathogen with increased MICs of the respective drugs could be demonstrated for Streptococcus pneumoniae , no such correlation was found for H. influenzae . It is proposed that susceptibility breakpoints forH. influenzae should be considerably lower than the current ones for both cefaclor and azithromycin for AOM caused by H. influenzae This r and omized , multicentre prospect i ve study was undertaken to compare the efficacy and tolerance of a one day course of injectable cefotaxime with a five day oral course of co-amoxyclav ( amoxycillin plus clavulanic acid ) in the treatment of acute otitis media in children . The study was conducted in 116 patients between the ages of three months and 12 years . No significant difference in efficacy was observed between the two treatment groups , but tolerance to the treatments differed significantly . There were no unwanted side-effects in the cefotaxime group whereas 22 % of children in the amoxycillin plus clavulanic acid group suffered side-effects ( P 0.0007 ) . Short-course antibiotic therapy with cefotaxime appears to be a valuable alternative to conventional treatment regimens for acute otitis media in children OBJECTIVE To determine if parents prefer single-dose intramuscular ( IM ) therapy or st and ard 10-day oral therapy for treatment of acute otitis media ( AOM ) . DESIGN Parents were asked their preference at the time their child was enrolled in a r and omized controlled trial comparing the clinical efficacy of single-dose IM ceftriaxone sodium with 10 days of oral amoxicillin and clavulanate potassium for AOM . Additional information was collected at days 3 to 5 and 14 to 16 after the initiation of the therapy . SETTING Primarily private practice s ; 15 sites . PATIENTS For this study , 648 children aged 3 months to 6 years were r and omly assigned to receive IM ( n=327 ) or oral ( n=321 ) therapy . RESULTS The groups were equivalent in all measured sociodemographic factors . At the time of enrollment , 85 % of parents expressed a preference for single-dose IM therapy . At days 3 to 5 , no differences were reported in days children were absent from school or day care , parental absence from work , or loss of sleep by children . However , more parents with children in the IM therapy group than in the oral therapy group reported loss of sleep by the parent ( 35 % vs 26 % , P=.02 , chi(2 ) ) . At days 14 to 16 , more parents with children in the IM group reported being " very satisfied " with the antibiotic ( 65 % ) compared with parents whose children were assigned to the oral therapy group ( 38 % , P<.001 ) . In comparing current therapy to past oral therapy for AOM , 71 % of the parents with children in the IM therapy group reported more satisfaction with current therapy , in contrast to 21 % of parents with children in the oral therapy group ( P<.001 ) . Of the parents , 83 % indicated they would prefer single-dose IM therapy for AOM in the future . CONCLUSION All of the parents prefer single-dose IM therapy for AOM over st and ard 10-day oral therapy BACKGROUND Acute otitis media ( AOM ) is a common childhood infection that is frequently treated by antibiotics . There are no prospect i ve and comprehensive trials evaluating childhood AOM for etiologic pathogens and resistance pattern in Turkey . The aims of the study were to determine the bacterial etiologies and resistance patterns , and identify the efficacy and the relapse rates of 3 days of azitromycin and 10 days of cefaclor therapy in AOM . METHODS This prospect i ve , r and omized , single-blind , open study was carried out in 78 cases of AOM . Mean age was 30.7+/-27 months . Tympanocentesis and aspiration of middle ear fluid ( MEF ) were used to obtain purulent material from the middle ear . Group 1 consisted of the cases ( n=41 ) on azitromycin therapy and Group 2 ( n=37 ) on cefaclor . Dosage of azitromycin was 10 mg/kg per day for 3 days and cefaclor 40 mg/kg per day for 10 days . The patients were evaluated on days 3 - 5 ( second visit ) , day 10 ( third visit ) , and day 30 ( fourth visit ) during follow-up . RESULTS A total of 50 species were isolated from 44 of 78 cases from which material s were obtained ( 44/78 ; 56.4 % ) . Most frequently isolated microorganism was Streptococcus pneumoniae ( n=18 ; 36 % ) , followed by Haemophilus influenzae ( n=11 ; 22 % ) , S. aureus ( n=9 ; 18 % ) , Moraxella catarrhalis ( n=4 ; 8 % ) , and group A beta-hemolytic streptococcus ( GAS , n=4 ; 8 % ) . Enterococcus faecalis was isolated from three cases and H. parainfluenzae from one . Penicillin and amoxicillin resistances of bacteria were found to be 40 and 36 % , respectively . The frequency of penicillin and amoxicillin resistance in < /=24-month age group was 59 and 66.6 % , respectively . The patients did not demonstrate significant differences in terms of cure rate on the third to fifth day ( Group 1 : 32.5 % ; Group 2 : 36.4 % ) , 10th day ( Group 1 : 76.9 % ; Group 2 : 84.8 % ) , and on 30th day ( Group 1 : 91.3 % ; Group 2 : 81.8 % ) . There were no significant differences with respect to side effects , relapse , and re-infection rate between the two groups . CONCLUSION In more than half of the AOM cases , bacteria were isolated from MEF and most frequently isolated organisms were S. pneumoniae , H. influenzae , and S. aureus . Three-day azitromycin therapy was as effective as 10-day cefaclor therapy A total of 371 children , aged 6 months to 12 years , with acute otitis media , acute sinusitis , streptococcal tonsillitis/pharyngitis , or pneumonia were included in an open , multicenter study . Among them , 192 children were r and omized to receive azithromycin for 3 days ( 10 mg/kg daily ) , and 179 for 5 days ( 10 mg/kg on day 1 and 5 mg/kg on days 2 - 5 ) . The overall clinical cure rate was 95.7 % and 96.1 % , and bacteriological eradication rate 90.1 % and 94.2 % in the 3-day and 5-day groups , respectively . Side effects , mostly mild gastrointestinal disturbances , were observed in 5.3 % of children from the 3-day , and 6.7 % from the 5-day group . Only in one child ( 0.3 % ) was therapy discontinued due to vomiting . The results of this study demonstrate that 3-day and 5-day azithromycin courses have comparable efficacy and tolerability in children with respiratory infections IN RECENT years a number of authors —this author among them — have called for restricting , in varying degree , the use of antimicrobials in treating otitis media . 1 - 5 Two factors have prompted these recommendations : compelling evidence that selective pressure from antimicrobial use contributes importantly to the rising prevalence of infections caused by multidrug resistant Streptococcus pneumoniae , 6,7 and the fact that otitis media accounts for a large proportion of all antimicrobial use . For example , in 1986 , of 44.5 million office-based prescriptions for antimicrobials for children younger than 10 years , 42 % were for otitis media 8 ; while in 1990,1 or more drugs — mainly antimicrobials — were prescribed at more than 80 % of the estimated 24.5 million visits to physicians ' offices for otitis media . 9,10 Of those visits , children younger than 2 years accounted for 33.3 % ; children aged 2 to 5 years , 29.2 % ; and children aged 6 to 14 years , 17.9 % . 9 In a recent prospect i ve study , Ninety-six children with acute otitis media were r and omized into a double-blind general practice trial of three-day and seven-day courses of cefaclor 125 mg tds . These regimens were equally effective in terms of resolution of symptoms and signs of otitis media , even in children presenting with bulging of the tympanic membrane . There was no difference between the groups in the recurrence of middle-ear infection during the six weeks after entry to the trial . The results provide further evidence about the effectiveness of short courses of antibiotics for children with presumed middle-ear infection We conducted a controlled clinical trial to determine the efficacy of single-dose intramuscular ceftriaxone for the treatment of acute otitis media . Fifty-four children aged 18 months to 6 years with clinical and tympanometric evidence of otitis media were r and omized to receive either 50 mg/kg ceftriaxone or 10 days of oral cefaclor 40 mg/kg/day . Resolution of symptoms and clinical and tympanometric appearance of the tympanic membrane at follow-up visits were used to determine outcome . Thirty-one children received ceftriaxone and 23 received oral cefaclor . There were no treatment failures . There were no significant differences between groups in persistence of effusion or recurrence of acute otitis media . We conclude that a single intramuscular dose of ceftriaxone compares favorably with 10 days of oral cefaclor for the treatment of acute otitis media The efficacy and safety of azithromycin and clarithromycin were compared in an open multicentre study involving 380 adult patients with acute otitis media , acute sinusitis , or acute streptococcal pharyngitis or tonsillitis . Patients were assigned r and omly to receive azithromycin as a single dose of 500 mg daily for three days , or clarithromycin 250 mg bid for ten days . Overall clinical efficacy was found to be similar in each treatment group at day 10 - 14 , with a satisfactory outcome ( cured or improved ) in 95 % of azithromycin and 96 % of clarithromycin patients . Bacteriological efficacy was also similar , with eradication of the pathogen in 94 % and 95 % of isolates , respectively , in the azithromycin and clarithromycin groups . In otitis media , a satisfactory clinical response was seen in 97 % of patients in each treatment group . Azithromycin therapy result ed in a clinical response rate of 93 % in sinusitis patients , with bacteriological eradication in 93 % of patients . Two patients ( who were cured clinical ly ) had persistent pathogens . Similarly , clarithromycin achieved clinical response and bacteriological eradication in 95 % and 92 % of sinusitis patients , respectively . Pathogens persisted in two patients with clinical cure , and in one case of clinical failure . In pharyngitis or tonsillitis , Streptococcus pyogenes was eradicated successfully in 95 % of patients in both groups , and the clinical success rates were 96 % and 97 % for azithromycin and clarithromycin , respectively . No case of clinical failure was associated with persistence of S. pyogenes infection . At the follow-up assessment of this diagnosis group , reinfection had occurred in three ( 8 % ) azithromycin patients and one ( 3 % ) clarithromycin patient , and all but one patient remained asymptomatic . Both drugs were well-tolerated , with 8.4 % of patients on azithromycin and 7.4 % on clarithromycin reporting adverse events , mainly gastrointestinal . It was concluded that a three-day course of azithromycin was as effective and well-tolerated as a ten-day course of clarithromycin in adults with acute upper respiratory tract infections A double blind study comparing a single dose of amoxicillin versus a 10-day course of amoxicillin in the treatment of acute otitis media ( AOM ) was undertaken . All children diagnosed with AOM in a pediatric clinic were requested to participate . After tympanocentesis was performed , patients were r and omly assigned to receive either amoxicillin ( 100 mg/kg ) followed by placebo every 8 hours for 10 days or placebo followed by amoxicillin ( 40 mg/kg/D ) for 10 days . Patients returned to clinic on days 3 and 10 post-treatment . Seventeen patients were enrolled : 7 received single dose therapy and 10 received 10 days of therapy . There were no failures in the control group and 3 failures in the single dose group ( day 5 , day 6 , and 11 ) ( p = 0.05 ) . Middle ear isolates included : S. pneumoniae 7 , H. influenzae 4 , B. catarrhalis 1 , and no pathogen in 5 . Due to the significant number of failures in the treatment group , the study was prematurely terminated Azithromycin and cefaclor were compared for the treatment of acute otitis media , streptococcal pharyngitis/tonsillitis , or sinusitis in an open multicentre study conducted in 530 adults . At the end of therapy ( day 11 - 15 ) , 228/245 ( 93 % ) patients treated with azithromycin 500 mg once daily for 3 days and 233/241 ( 97 % ) treated with cefaclor 250 mg given three times daily for 10 days were considered to have responded satisfactorily ( cured or improved ) . In bacteriologically evaluable patients with pharyngitis/ tonsillitis , Streptococcus pyogenes was eradicated in 116/117 ( 99 % ) azithromycin- and in 115/119 ( 97 % ) cefaclor-treated patients at day 11 - 15 ; one patient in each group had become reinfected after initial eradication of the pathogen . When followed up on day 25 - 30 , S. pyogenes infection had recurred in 5/105 ( 5 % ) azithromycin and 4/108 ( 3 % ) cefaclor patients who had responded satisfactorily at day 11 - 15 , and whose baseline pathogen had been eradicated . Of these patients , two in the azithromycin and one in the cefaclor group also relapsed clinical ly ; the others remained asymptomatic . Patients tolerated both treatments well ; treatment-related adverse events were recorded in 11 % of the 267 azithromycin- and 10 % of the 263 cefaclor-treated patients assessed for safety . One azithromycin patient and five cefaclor patients withdrew because of adverse events . The results of the study show that a 3-day regimen of azithromycin , given once daily , is as effective and well tolerated as a multiple-daily , 10-day cefaclor regimen for the treatment of upper respiratory tract infections in adults A comparison was made of the clinical effectiveness of azithromycin ( once daily for three days at a dose of 10 mg/kg in children or 500 mg/day in adults ) and amoxicillin/clavulanic acid and cefaclor ( st and ard doses for 7 to 14 days ) in acute ear , nose and throat infections in an open r and omized study . The group with azithromycin included 37 otitis media , 24 pharyngotonsillitis and 6 maxillary sinusitis ( n = 67 ) . The amoxicillin/clavulanic acid group , 22 otitis media , 19 pharyngotonsillitis and 6 maxillary sinusitis ( n = 47 ) and the cefaclor group , 15 otitis media , 12 pharyngotonsillitis and 4 maxillary sinusitis ( n = 31 ) . Fifteen days after beginning treatment , 97 % ( 65/67 ) of the patients who received azithromycin had improved or cured , compared with 85 % ( 40/47 ) of those who received amoxicillin/clavulanic acid and 84 % ( 26/31 ) , cefaclor ( p < 0.02 ) . Pathogens were not eradicated in 3 % ( 2/58 ) of the patients who received azithromycin , compared with 13 % ( 4/28 ) who received amoxicillin/clavulanic acid and 15 % ( 4/28 ) cefaclor . Patients with azithromycin showed an earlier clinical improvement and more rapid normalization of the leukocyte count , erythrocyte sedimentation rate and acute phase proteins . No patient with azithromycin had adverse effects , versus 15 % ( 7/47 ) for patients with amoxicillin/clavulanic acid and 16 % ( 5/31 ) for cefaclor . Treatment compliance was 100 , 83 ( 39/47 ) and 84 % ( 26/31 ) , respectively ( p < 0.01 ) . We conclude that azithromycin treatment for three days is faster and more effective clinical ly and analytically than st and ard treatment with amoxicillin/clavulanic acid or cefaclor in acute infections of the ear , nose and throat BACKGROUND Acute otitis media ( AOM ) is one of the most common acute bacterial infection in childhood and also the most frequent reason for outpatient antibiotic therapy . Little recent information about susceptibility patterns of AOM bacterial pathogens in Turkish children has been reported . OBJECTIVE To determine the bacterial etiology of acute otitis media in children and to compare the efficiency of 3 days course of azithromycin with a 10 days course of amoxicillin-clavulanate . METHODS This prospect i ve , single blind , r and omised comparative study was carried out in 180 children with AOM . Paracentesis was performed for middle ear fluid culture before the first dose antibiotic therapy . Children with acute otitis media were r and omised to receive either low dose amoxicillin-clavulanate ( 45/6.4 mg/kg/day in two divided doses for 10 days ) or low dose azithromycin ( 10mg/kg/day for 3 days ) . Clinical response was assessed on days 2 - 4 , 11 - 13 , 26 - 28 . RESULTS Bacterial pathogens were isolated from 108 ( 60 % ) of 180 children . Streptococcus pneumoniae was the most common isolated pathogen ( 39.7 % ) , followed by Haemophilus influenzae ( 20.7 % ) , Moraxella catarrhalis ( 15.5 % ) , Staphylococcus aureus ( 13.8 % ) , Group A beta-hemolytic streptococcus ( 5.1 % ) , Escherichia coli ( 3.4 % ) and Enterococcus faecalis ( 1.7 % ) . This study demonstrated low resistance rates compared to studies of different countries . Although clinical response rates were better in patients treated with amoxicillin-clavulanate , this was not statistically significant [ 86.6 % ( 78 of 90 ) ] versus [ 95.2 % ( 80 of 84 ) ] . Success rates of amoxicillin-clavulanate were high for both S. pneumoniae and H. influenzae . Difference between success rates was not statistically significant ( P=0.144 and 0.352 ) . CONCLUSIONS Bacteria were isolated in 60 % of AOM cases . The clinical efficiency of amoxicillin-clavulanate was found to be equal compared to azithromycin in children with acute otitis media An open , multicentre study involving 259 children between 6 months and 13 years of age was performed to assess the efficacy and safety of azithromycin and to compare it with cefaclor as treatment of acute otitis media . Patients were r and omized to receive either azithromycin 10 mg/kg once daily for 3 days or cefaclor 40 mg/kg daily in divided doses every 8 h for 10 days . Cure or improvement in signs and symptoms was observed in 112/114 ( 98 % ) evaluable azithromycin-treated patients and 116/120 ( 97 % ) evaluable cefaclor-treated patients on days 11 - 15 . In contrast to cefaclor , however , azithromycin was associated with a significantly ( P = 0.033 ) higher cure rate 1 month after completion of treatment . In those patients who were followed up to days 25 - 30 , the response was satisfactory ( cure or improvement ) in 31/32 ( 97 % ) patients who had received azithromycin and in 31/36 ( 86 % ) to whom cefaclor had been administered . Patients tolerated both treatments well and no severe adverse events related to therapy were recorded in either group . The results of this study show that a 3-day , once-daily regimen of azithromycin has comparable clinical efficacy and tolerability to a thrice-daily course of cefaclor administered for 10 days , but the azithromycin is associated with a lower incidence of relapse |
708 | 14,583,986 | REVIEW ER 'S CONCLUSIONS There is insufficient evidence to determine the effects of interventions to modify environmental home hazards . | BACKGROUND Injury in the home is extremely common , accounting for around a third of all injuries .
The majority of injuries of children under five and people aged 75 and over occur at home .
Multi-factorial injury prevention interventions have been shown to reduce injuries in the home .
However , few studies have focussed specifically on the impact of physical adaptations to the home environment and the effectiveness of such intervention needs to be ascertained .
OBJECTIVES To review the evidence for the effect on injuries of modification of the home environment with a primary focus on interventions to reduce physical hazards . | OBJECTIVE to evaluate a nurse-led management plan and care pathway for older people discharged from an Accident and Emergency Department after a fall . DESIGN r and omized controlled trial . SETTING a large teaching hospital . SUBJECTS 348 consecutive patients aged 65 or over attending the Accident and Emergency Department with a fall . INTERVENTIONS we r and omized patients to falls nurse intervention or usual care . Within 4 weeks , the intervention group received a home assessment to address easily modifiable risk factors for falls . This included assessment s of medication , ECG , blood pressure , cognition , visual acuity , hearing , vestibular dysfunction , balance , mobility , feet and footwear . All patients were given advice and education about general safety in the home . MAIN OUTCOME MEASURES Further falls , functional ability , re-attendance at the Accident and Emergency Department and admission to hospital . RESULTS at 6 months post-Index fall , 36 patients in the intervention group and 39 patients in the control group had had 89 and 145 falls respectively . Although the intervention group had less falls , this was not significant ( P>0.05 ) . Similarly , the intervention group had fewer fall-related admissions and bed days ( 8 and 69 respectively ) than the control group ( 10 and 233 respectively ) . The intervention group scored significantly higher in indicators of function ( P<0.05 ) and mobility within the community ( P<0.02 ) . CONCLUSIONS although the differences were not significant , patients in the intervention group had fewer falls , less hospital attendances and spent less time in hospital . Moreover , patients in the intervention group were more functionally independent at 6 months post-Index fall STUDY OBJECTIVE In the causative mechanism of falls among older community dwellers , slips and trips have been found to be significant precursors . The purpose of the two year trial was to assess the effectiveness of multi-component interventions targeting major risk factors for falls in reducing the incidence of slips , trips and falls among the well , older community . DESIGN Four groups with approximately equal numbers of participants were r and omly allocated to interventions . The prevention strategies included education and awareness raising of falls risk factors , exercise sessions to improve strength and balance , home safety advice to modify environmental hazards , and medical assessment to optimise health . The interventions combined the strategies in an add on approach . The first intervention group receiving the information session only was regarded as the control . The outcome of interest was the occurrence of a slip , trip or fall , monitored prospect ively using a daily calendar diary . PARTICIPANTS AND SETTING Two hundred and fifty two members of the National Seniors Association in the Brisbane district agreed to participate . National Seniors clubs provide a forum for active , community dwelling Australians aged 50 and over to participate in policy , personal development and recreation . MAIN RESULTS Using Cox 's proportional hazards regression model , adjusted hazard ratios comparing intervention groups with the control ranged from 0.35 ( 95 % CI 0.17 , 0.73 ) to 0.48 ( 0.25 , 0.91 ) for slips ; 0.29 ( 0.16 , 0.51 ) to 0.45 ( 0.27 , 0.74 ) for trips ; and 0.60 ( 0.36 , 1.01 ) to 0.82 ( 0.51 , 1.31 ) for falls . While calendar monitoring recorded outcome , it was also assessed as a prevention strategy by comparing the intervention groups with a hypothetical non-intervened group . At one year after intervention , reductions in the probability of slips , trips and falls ( 61(95%CI 54 , 66)% ; 56 ( 49 , 63)% ; 29 ( 22 , 36)% respectively ) were demonstrated . CONCLUSIONS This study makes an important contribution to the priority community health issue of falls prevention by showing that effective , sustainable , low cost programmes can be introduced through community-based organisations to reduce the incidence of slips , trips and falls in well , older people BACKGROUND Falls in elderly people are a common presenting complaint to accident and emergency departments . Current practice commonly focuses on the injury , with little systematic assessment of the underlying cause , functional consequences , and possibilities for future prevention . We undertook a r and omised controlled study to assess the benefit of a structured inderdisciplinary assessment of people who have fallen in terms of further falls . METHODS Eligible patients were aged 65 years and older , lived in the community , and presented to an accident and emergency department with a fall . Patients assigned to the intervention group ( n=184 ) underwent a detailed medical and occupational-therapy assessment with referral to relevant services if indicated ; those assigned to the control group ( n=213 ) received usual care only . The analyses were by intention to treat . Follow-up data were collected every 4 months for 1 year . FINDINGS At 12-month follow-up , 77 % of both groups remained in the study . The total reported number of falls during this period was 183 in the intervention group compared with 510 in the control group ( p=0.0002 ) . The risk of falling was significantly reduced in the intervention group ( odds ratio 0.39 [ 95 % CI 0.23 - 0.66 ] ) as was the risk of recurrent falls ( 0.33 [ 0.16 - 0.68 ] ) . In addition , the odds of admission to hospital were lower in the intervention group ( 0.61 [ 0.35 - 1.05 ] ) whereas the decline in Barthel score with time was greater in the control group ( p<0.00001 ) . INTERPRETATION The study shows that an interdisciplinary approach to this high-risk population can significantly decrease the risk of further falls and limit functional impairment The importance of environmental hazards in the home as risk factors for falls and fractures is uncertain . A case-control study was conducted , involving people aged 65 years and over referred to an occupational therapy department for home assessment . There were 52 subjects with a recent hip fracture , 43 fallers ( subjects with two or more falls in the past year but no hip fracture ) , and 157 non-fallers ( subjects without hip fracture and with fewer than two falls in the past year ) . Subjects ' homes were assessed for environmental hazards by occupational therapists using a structured home assessment form comprising 35 potential hazards . Overall , the homes of fallers were no more hazardous than the homes of non-fallers . However , fallers with cognitive impairment had significantly more hazards in their homes than non-fallers with cognitive impairment . A wide range of environmental hazards was associated with hip fractures . Many of the findings of this study could be due to bias inherent in the case-control design . To overcome the inadequacies of observational studies for the investigation of home hazards and falls , r and omized trials are recommended to determine if removing hazards reduces the risk of falls and fractures OBJECTIVES To evaluate the effectiveness of a multifaceted , nonpharmaceutical intervention on incidence of falls and fallers . DESIGN Prospect i ve , cluster-r and omized , controlled 12-month trial . SETTING Six community nursing homes in Germany . PARTICIPANTS Long-stay residents ( n = 981 ) aged 60 and older ; mean age 85 ; 79 % female . INTERVENTIONS Staff and resident education on fall prevention , advice on environmental adaptations , progressive balance and resistance training , and hip protectors . MEASUREMENTS Falls , fallers , and fractures . RESULTS The incidence density rate of falls per 1,000 resident years ( RY ) was 2,558 for the control group ( CG ) and 1,399 for the intervention group ( IG ) ( relative risk ( RR ) = 0.55 , 95 % confidence interval ( CI ) = 0.41 - 0.73 ) . Two hundred forty-seven ( 52.3 % ) fallers were detected in the CG and 188 ( 36.9 % ) in the IG ( RR = 0.75 , 95 % CI = 0.57 - 0.98 ) . The incidence density rate of frequent fallers ( > 2/year ) was 115 ( 24.4 % ) for the CG and 66 ( 13.0 % ) for the IG ( RR = 0.56 , 95 % CI = 0.35 - 0.89 ) . The incidence density rate of hip fractures per 1,000 RY was 39 for the CG and 43 for the IG ( RR = 1.11 , 95 % CI = 0.49 - 2.51 ) . Other fractures were diagnosed with an incidence density rate of 52 per 1,000 RY for CG and 41 per 1,000 RY for IG ( RR = 0.78 , 95 % CI = 0.57 - 1.07 ) . CONCLUSION The incidence density rate of falls and fallers differed considerably between the control and intervention groups . The study was underpowered to demonstrate a significant difference of hip or nonhip fractures . Because of a low fracture rate in both groups , the investigation of fracture rates would have required a larger sample size to detect an effect of the intervention OBJECTIVE To assess the effectiveness of an emergency department (ED)-based home safety intervention on caregivers ' behaviors and practice s related to home safety . METHODS We conducted a r and omized , clinical trial of 96 consecutive caregivers of children who were younger than 5 years and presented to an urban pediatric ED for evaluation of an acute unintentional injury sustained in the home . After completing a structured home safety question naire via face-to-face interview , caregivers were r and omly assigned to receive either comprehensive home safety education and free safety devices or focused , injury-specific ED discharge instructions . Participants were contacted by telephone 2 months after the initial ED visit for repeat administration of the safety question naire . The pretest and posttest question naires were scored such that the accrual of points correlated with reporting of safer practice s. Scores were then normalized to a 100-point scale . The overall safety score reflected performance on the entire question naire , and the 8 category safety scores reflected performance in single areas of home injury prevention ( fire , burn , poison , near-drowning , aspiration , cuts/piercings , falls , and safety device use ) . The main outcome was degree of improvement in safety practice s as assessed by improvement in safety scores . RESULTS The intervention group demonstrated a significantly higher average overall safety score at follow-up than the control group ( 73.3 % + /- 8.4 % vs 66.8 % + /-11.1 ) and significant improvements in poison , cut/piercing , and burns category scores . Caregivers in the intervention group also demonstrated greater improvement in reported use of the distributed safety devices . CONCLUSIONS This educational and device disbursement intervention was effective in improving the home safety practice s of caregivers of young children . Moreover , the ED was used effectively to disseminate home injury prevention information Abstract Objective : To determine the effectiveness of multifactorial intervention after a fall in older patients with cognitive impairment and dementia attending the accident and emergency department . Design : R and omised controlled trial . Participants : 274 cognitively impaired older people ( aged 65 or over ) presenting to the accident and emergency department after a fall : 130 were r and omised to assessment and intervention and 144 were r and omised to assessment followed by conventional care ( control group ) . Setting : Two accident and emergency departments , Newcastle upon Tyne . Main outcome measures : Primary outcome was number of participants who fell in year after intervention . Secondary outcomes were number of falls ( corrected for diary returns ) , time to first fall , injury rates , fall related attendances at accident and emergency department , fall related hospital admissions , and mortality . Results : Intention to treat analysis showed no significant difference between intervention and control groups in proportion of patients who fell during 1 year 's follow up ( 74 % ( 96/130 ) and 80 % ( 115/144 ) , relative risk ratio 0.92 , 95 % confidence interval 0.81 to 1.05 ) . No significant differences were found between groups for secondary outcome measures . Conclusions : Multifactorial intervention was not effective in preventing falls in older people with cognitive impairment and dementia presenting to the accident and emergency department after a fall . What is already known on this topic Multifactorial intervention prevents falls in cognitively normal older people living in the community and in those who present to the accident and emergency department after a fall Fall prevention strategies have not been tested by controlled trials in patients with cognitive impairment and dementia who fall What this study adds No benefit was shown from multifactorial assessment and intervention after a fall in patients with cognitive impairment and dementia presenting to the accident and emergency department The intervention was less effective in these patients than in cognitively normal older Parents of 171 children coming to the Yale-New Haven Hospital Primary Care Center for their 6-month checkup were r and omized into an intervention group ( n = 85 ) and a control group ( n = 86 ) . Parents in the intervention group received a three-part individualized course in child safety that required active parental participation . Parts 1 , 2 , and 3 were given at the 6-month , 9-month , and 12-month well-child visits , respectively . Parents in the control group received routine safety education as provided at well-child visits . The educational phase of the study was completed by 129 families , 65 in the intervention group and 64 in the control group . Safety knowledge , number of hazards in the home , and reported accidents were assessed by a " blinded " community health worker approximately 1 month after the 12-month well-child visit . A total of 109 home visits were made , 55 for the intervention group and 54 for the control group . Parental safety knowledge was assessed based upon pictorial hazard recognition . Of 13 possible hazards , the mean number of hazards recognized by the intervention group parents was 9.4 ( n = 55 ) v 8.4 ( n = 50 ) by the control group parents ( t = 2.1 , P less than .05 , two-tailed ) . A hazard score was determined for each family based on nine possible hazards observed at the home visit . The mean hazard score for the intervention group was 2.4 ( n = 55 v 3.0 ( n = 54 ) for the control group ( t = 2.4 , P less than .02 , two-tailed ) . Parentally reported accidents and accidents reported in hospital records were similar for both groups . Results of this study suggest that age-appropriate safety education that is repetitive and individualized and that requires active parental participation results in an increase in parental knowledge and an improvement in certain safety practice Abstract Objective : To evaluate whether a programme of multifactorial home visits reduces falls and impairments in mobility in elderly people living in the community . Design : R and omised controlled trial with 18 months of follow up . Setting : Six general practice s in Hoensbroek , the Netherl and s. Participants : 316 people aged 70 and over living in the community , with moderate impairments in mobility or a history of recent falls . Intervention : Five home visits by a community nurse over a period of one year . Visits consisted of screening for medical , environmental , and behavioural factors causing falls and impairments in mobility , followed by specific advice , referrals , and other actions aim ed at dealing with the observed hazards . Main outcome measures : Falls and impairments in mobility . Results : No differences were found in falls and mobility outcomes between the intervention and usual care groups . Conclusion : Multifactorial home visits had no effects on falls and impairments in mobility in elderly people at risk who were living in the community . Because falls and impairments in mobility remain a serious problem among elderly people , alternative strategies should be developed and evaluated Abstract Objective : To test the effectiveness of , and explore interactions between , three interventions to prevent falls among older people . Design : A r and omised controlled trial with a full factorial design . Setting : Urban community in Melbourne , Australia . Participants : 1090 aged 70 years and over and living at home . Most were Australian born and rated their health as good to excellent ; just over half lived alone . Interventions : Three interventions ( group based exercise , home hazard management , and vision improvement ) delivered to eight groups defined by the presence or absence of each intervention . Main outcome measure : Time to first fall ascertained by an 18 month falls calendar and analysed with survival analysis techniques . Changes to targeted risk factors were assessed by using measures of quadriceps strength , balance , vision , and number of hazards in the home . Results : The rate ratio for exercise was 0.82 ( 95 % confidence interval 0.70 to 0.97 , P=0.02 ) , and a significant effect ( P<0.05 ) was observed for the combinations of interventions that involved exercise . Balance measures improved significantly among the exercise group . Neither home hazard management nor treatment of poor vision showed a significant effect . The strongest effect was observed for all three interventions combined ( rate ratio 0.67 ( 0.51 to 0.88 , P=0.004 ) ) , producing an estimated 14.0 % reduction in the annual fall rate . The number of people needed to be treated to prevent one fall a year ranged from 32 for home hazard management to 7 for all three interventions combined . Conclusions : Group based exercise was the most potent single intervention tested , and the reduction in falls among this group seems to have been associated with improved balance . Falls were further reduced by the addition of home hazard management or reduced vision management , or both of these . Cost effectiveness is yet to be examined . These findings are most applicable to Australian born adults aged 70–84 years living at home who rate their health as good BACKGROUND Multifaceted programs that combine assessment with interventions have been shown to reduce subsequent falls in some clinical trials . We tested this approach to see whether it would be effective if offered as a consultation service using existing health care re sources . METHODS The subjects of this r and omized controlled trial had to be aged 65 years or more and had to have fallen within the previous 3 months . They were r and omly assigned to receive either usual care or the intervention , which consisted of in-home assessment in conjunction with the development of an individualized treatment plan , including an exercise program for those deemed likely to benefit . The primary outcomes were the proportion of participants who fell and the rate of falling during the following year . Visits to the emergency department and admissions to hospital were secondary outcomes . RESULTS One hundred and sixty-three subjects were r and omly assigned to either the control or the intervention group , and 152 provided data about their falls . There were no significant differences between the control and intervention groups in the cumulative number of falls ( 311 v. 241 , p = 0.34 ) , having one or more falls ( 79.2 % v. 72.0 % , p = 0.30 ) or in the mean number of falls ( 4.0 v. 3.2 , p = 0.43 ) . Analysis of secondary outcomes ( health care use ) also showed no significant differences between the intervention group and the control group . In the Cox regression analysis , there was no significant difference between the groups in the proportion of subjects having one or more falls ( p = 0.55 ) , but there was a significantly ( p < 0.001 ) longer time between falls in the intervention group . In a post hoc subgroup analysis , subjects with more than 2 falls in the 3 months preceding study entry who had been assigned to the intervention group were less likely to fall ( p = 0.046 ) and had a significantly longer time between falls ( p < 0.001 ) , when compared with the group who received usual care . INTERPRETATION The intervention did not decrease significantly the cumulative number of falls , the likelihood of participants having at least one fall over the next year or the mean number of falls . It did increase significantly the time between falls in a survival analysis when age , sex and history of falling were used as covariates BACKGROUND During the 20-month period September 1993 to April 1995 , a health education injury prevention programme focusing on home injuries among the young ( < or = 18 years old ) and elderly ( > or = 65 years old ) on the Greek isl and of Naxos was undertaken , its effectiveness was evaluated by comparing the subsequent injury experience in sentinel population groups in Naxos as well as in Spetses , another isl and of similar sociodemographic profile , where no such intervention programme had been formally implemented . METHODS On the isl and -of Naxos an injury prevention campaign was initially undertaken involving virtually all opinion leaders and implemented through lectures , workshops and publicity in the local media . The main intervention focused on 172 households on the isl and of Naxos and was done by trained local collaborators who visited each household weekly to provide injury prevention advice and assess home safety . Similar visits were done by untrained collaborators in 177 households on the isl and of Spetses in order to assure collaboration of household members in the comparative evaluation stage of the programme . The process evaluation was based on ascertained changes of safety features and attitudes in the participating households , whereas the outcome evaluation was based on the incidence of injuries among members of the participating households in the two isl and s over a period of 8.5 months ( 255 days ) . RESULTS On the intervention isl and of Naxos there were statistically significant improvements with respect to 11 of the 28 examined variables , whereas on the isl and of Spetses , such improvement was only noted for one variable . The age-adjusted incidence rate ratio of injuries overall among the target groups , contrasting the intervention and the control households was 0.85 with 90 % confidence interval ( CI ) : 0.69 - 1.05 . With respect to home accidents the corresponding ratio was 0.79 with 90 % CI : 0.60 - 1.04 . CONCLUSIONS An intensive and focused injury prevention intervention had only modest success when injuries themselves were the outcome variable Abstract Objective : To assess the effectiveness of safety advice at child health surveillance consultations , provision of low cost safety equipment to families receiving means tested state benefits , home safety checks , and first aid training on frequency and severity of unintentional injuries in children at home . Design : Cluster r and omised controlled trial . Setting : 36 general practice s in Nottingham . Subjects : All children aged 3 - 12 months registered with participating practice s. Interventions : A package of safety advice at child health surveillance consultations at 6 - 9 , 12 - 15 , and 18 - 24 months;provision of low cost safety equipment to families on means tested state benefits ; and home safety checks and first aid training by health visitors . Outcome measures : Primary outcomes measures were frequency and severity of medically attended injuries . Secondary outcome measures were self reported safety practice s , possession and use of safety equipment , knowledge and confidence in dealing with first aid , and perceptions of risk of injury and risk of hazards assessed by postal question naire at baseline and follow up at 25 months . Results : At baseline , both groups had similar risk factors for injury , sociodemographic characteristics , safety practice s , possession and use of safety equipment , knowledge and confidence in dealing with first aid , and perceptions of risk . No significant difference was found in frequency of at least one medically attended injury ( odds ratio 0.97 , 95 % confidence interval 0.72 to1.30 ) , at least one attendance at an accident and emergency department for injury ( , 0.76 to 1.37 ) , at least one primary care attendance for injury ( 0.75 , 0.48 to 1.17 ) , or at least one hospital admission for injury ( 0.69 , 0.42 to 1.12 ) . No significant difference in the secondary outcome measures was found between the intervention and control groups . Conclusions : The intervention package was not effective in reducing the frequency of minor unintentional injuries in children at home , and larger trials are required to assess the effect on more severe injuries OBJECTIVES To evaluate the outcome of an intervention to reduce hazards in the home on the rate of falls in seniors . DESIGN R and omized controlled trial , with follow-up of subjects for 1 year . SETTING Community-based study in Perth , Western Australia . PARTICIPANTS People age 70 and older . INTERVENTION One thous and eight hundred seventy-nine subjects were recruited and r and omly allocated by household to the intervention and control groups in the ratio 1:2 . Because of early withdrawals , 1,737 subjects commenced the study . All members of both groups received a single home visit from a research nurse . Intervention subjects ( n = 570 ) were offered a home hazard assessment , information on hazard reduction , and the installation of safety devices , whereas control subjects ( n = 1,167 ) received no safety devices or information on home hazard reduction . MEASUREMENTS Both groups recorded falls on a daily calendar . Reported falls were confirmed by a semistructured telephone interview and were assigned to one of three overlapping categories : all falls , falls inside the home , and falls involving environmental hazards in the home . Analysis was by multivariate modelling of rate ratios and odds ratios for falls , corrected for household clustering , using Poisson regression and logistic regression with robust variance estimation . RESULTS Overall , 86 % of study subjects completed the 1 year of follow-up . The intervention was not associated with any significant reduction in falls or fall-related injuries . There was no significant reduction in the intervention group in the incidence rate of falls involving environmental hazards inside the home ( adjusted rate ratio , 1.11 ; 95 % CI = 0.82 - 1.50 ) , or the proportion of the intervention group who fell because of hazards inside the home ( adjusted odds ratio , 0.97 ; 95 % CI = 0.74 - 1.28 ) . No reduction was seen in the rate of all falls ( adjusted rate ratio , 1.02 ; 95 % CI = 0.83 - 1.27 ) or the rate of falls inside the home ( adjusted rate ratio , 1.17 ; 95 % CI = 0.85 - 1.60 ) . There was no significant reduction in the rate of injurious falls in intervention subjects ( adjusted rate ratio , 0.92 ; 95 % CI = 0.73 - 1.14 ) . CONCLUSIONS The intervention failed to achieve a reduction in the occurrence of falls . This was most likely because the intervention strategies had a limited effect on the number of hazards in the homes of intervention subjects . The study provides evidence that a one-time intervention program of education , hazard assessment , and home modification to reduce fall hazards in the homes of healthy older people is not an effective strategy for the prevention of falls in seniors OBJECTIVE To present the results of an intervention trial to enhance parents ' home-safety practice s through pediatric safety counseling , home visits , and an on-site children 's safety center where parents receive personalized education and can purchase reduced-cost products . DESIGN Pediatricians were r and omized to a st and ard- or an enhanced-intervention group . Parents of their patients were enrolled when the patient was 6 months or younger and observed until 12 to 18 months of age . SETTING A hospital-based pediatric resident continuity clinic that serves families living in low-income , inner-city neighborhoods . PARTICIPANTS First- and second-year pediatric residents and their patient-parent dyads . INTERVENTIONS Parents in the st and ard-intervention group received safety counseling and referral to the children 's safety center from their pediatrician . Parents in the enhanced-intervention group received the st and ard services plus a home-safety visit by a community health worker . OUTCOMES Home observers assessed the following safety practice s : reduction of hot-water temperature , poison storage , and presence of smoke alarms , safety gates for stairs , and ipecac syrup . RESULTS The prevalence of safety practice s ranged from 11 % of parents who stored poisons safely to 82 % who had a working smoke alarm . No significant differences in safety practice s were found between study groups . However , families who visited the children 's safety center compared with those who did not had a significantly greater number of safety practice s ( 34 % vs 17 % had > or 3 ) . CONCLUSIONS Home visiting was not effective in improving parents ' safety practice s. Counseling coupled with convenient access to reduced-cost products appears to be an effective strategy for promoting children 's home safety Abstract Objective : To assess effectiveness of general practitioner advice about child safety , and provision of low cost safety equipment to low income families , on use of safety equipment and safe practice s at home . Design : R and omised , unblinded , controlled trial with initial assessment and six week follow up by telephone survey . Twenty families from intervention and control groups were r and omly selected for a home visit to assess validity of responses to second survey . Setting : A general practice in Nottingham . Subjects : 98 % ( 165/169 ) of families with children aged under 5 years registered with the practice . Interventions : General practitioner safety advice plus , for families receiving means tested state benefits , access to safety equipment at low cost . Control families received usual care . Main outcome measures : Possession and use of safety equipment and safe practice s at home . Results : Before intervention , the two groups differed only in possession of fireguards . After intervention , significantly more families in intervention group used fireguards ( relative risk 1.89 , 95 % confidence interval 1.18 to 2.94 ) , smoke alarms ( 1.14 , 1.04 to 1.25 ) , socket covers ( 1.27 , 1.10 to 1.48 ) , locks on cupboards for storing cleaning material s ( 1.38 , 1.02 to 1.88 ) , and door slam devices ( 3.60 , 2.17 to 5.97 ) . Also , significantly more families in intervention group showed very safe practice in storage of sharp objects ( 1.98 , 1.38 to 2.83 ) , storage of medicines ( 1.15 , 1.03 to 1.28 ) , window safety ( 1.30 , 1.06 to 1.58 ) , fireplace safety ( 1.84 , 1.34 to 2.54 ) , socket safety ( 1.77 , 1.37 to 2.28 ) , smoke alarm safety ( 1.11 , 1.01 to 1.22 ) , and door slam safety ( 7.00 , 3.15 to 15.6 ) . Stratifying results by receipt of state benefits showed that intervention was at least as effective in families receiving benefits as others . Conclusions : General practitioner advice , coupled with access to low cost equipment for low income families , increased use of safety equipment and other safe practice s. These findings are encouraging for provision of injury prevention in primary care . Key messages We assessed the effectiveness of general practitioner advice about child safety , and provision of low cost safety equipment to low income families , on safe practice s at home The intervention increased safe behaviour and use of safety equipment The intervention was equally effective in families receiving means tested benefits as in those not receiving benefits The effectiveness of this intervention should be evaluated over longer periods , in other practice s , and when delivered by other members of the primary healthcare OBJECTIVE To examine the effectiveness of a home visit program to improve home safety and decrease the frequency of injury in children . We examined the effects of the program on 1 ) parental injury awareness and knowledge ; 2 ) the extent that families used home safety measures ; 3 ) the rate of injury ; and 4 ) the cost effectiveness of the intervention . DESIGN A r and omized , controlled trial . SETTING A multicenter trial conducted at 5 hospitals in 4 Canadian urban centers . PARTICIPANTS Children < 8 years old , initially enrolled in an injury case-control study , were eligible to participate . Intervention . Subsequent to a home inspection conducted to determine baseline hazard rates for both groups , participants in the intervention group received a single home visit that included the provision of an information package , discount coupons , and specific instruction regarding home safety measures . MAIN RESULTS The median age was 2 years , with males comprising ~60 % of participants . The experimental groups were comparable at outset in terms of case-control status , age , gender , and socioeconomic status . Parental injury awareness and knowledge was high ; 73 % correctly identified injury as the leading cause of death in children , and an intervention effect was not demonstrated . The adjusted odds ratios ( ORs ) for the home inspection items indicated that significant safety modifications only occurred in the number of homes having hot water not exceeding 54 degrees C ( OR : 1.31 , 95 % confidence interval [ CI ] : 1.14 , 1.50 ) or the presence of a smoke detector ( OR : 1.45 , 95 % CI : 0.94 , 2.22 ) . However , the intervention group reported home safety modifications of 62 % at 4 months and significantly less injury visits to the doctor compared with the nonintervention group ( rate ratio : 0.75 ; 95 % CI : 0.58 , 0.96 ) . The total costs of care for injuries were significantly lower in the intervention group compared with the nonintervention group with a cost of $ 372 per injury prevented . CONCLUSIONS An intervention using a single home visit to improve the extent to which families use safety measures was found to be insufficient to influence the long-term adoption of home safety measures , but was effective to decrease the overall occurrence of injuries . Future programs should target a few , well-focused , evidence -based areas including the evaluation of high-risk groups and the effect of repeated visits on outcome Injuries in childhood are strongly related to poverty at the household level and to living in a deprived neighbourhood , but it is not clear whether these effects are independent . In this prospect i ve population study , all injuries to 5 - 14 year old children living in the city of Norwich , UK , and presented at the hospital Accident and Emergency Department over a 13 month period were recorded ( N=3526 ) . Information on the population of resident children and household composition was assembled from the health authority population register . Neighbourhood information was extracted from the census and local surveys . Unadjusted risks were calculated for individual and neighbourhood factors , followed by multilevel modelling in which predictors were included at three levels : individual , enumeration district and social area ( neighbourhood ) . The overall injury rate was 16.44 per 100 children per year . Injury rates between neighbourhoods varied two-fold and were highest in more deprived areas . In the final multilevel model injury risk was related to gender ( boys vs. girls OR=1.35 ) , age of child ( OR=1.07 per year ) , number of adults in the household ( OR=0.91 per adult ) , and age gap between child and eldest female ( 15 - 24 years vs. 25 - 34 years , OR=1.15 ) . Injury rates were also related to social area deprivation , although variations in injury rates between neighbourhoods were not wholly explained by deprivation . The adjusted odds ratio between the most and least deprived social areas was 1.35 . Excluding less serious injuries did not substantially change the results . The risks were very similar to those found in a previous study of pre-school children , with the same neighbourhoods identified as high and low risk as before . This evidence that neighbourhood factors independently influence injury risk over and above individual and household factors supports the use of area-based policies to reduce injuries in children To study prospect ively the injury patterns in under 14 year olds presenting to casualty . To use this information to assess the impact of a local Community Childhood Accident Prevention Project ( CCAPP ) Prospect i ve injury surveillance was collected on all attendees under 14 years of age . Casualty attendance for the members of the Safety Club and matched controls were analysed . Of the 4,267 attendees there was the expected male predominance . 2,261 ( 53 % ) of injuries occurred at home , 574 ( 13.5 % ) on the road , 553 ( 13 % ) at school with 202 ( 4.7 % ) during sports . Priority areas noted were high falls > 1 metre , road accidents , burns and poisonings . Those participating in the program demonstrated significantly ( p-value < 0.05 ) reduced admission rates and head injury rates when compared to non- participants . The above data base allows us to analyse injury patterns and to assess the success of an EU-sponsored local injury prevention campaign in areas of high social deprivation OBJECTIVES To evaluate the effectiveness of a multifactorial fall and injury prevention program in older people with higher and lower levels of cognition . DESIGN A preplanned subgroup comparison of the effectiveness of a cluster-r and omized , nonblinded , usual-care , controlled trial . SETTING Nine residential facilities in Umeå , Sweden . PARTICIPANTS All consenting residents living in the facilities , aged 65 and older , who could be assessed using the Mini-Mental State Examination ( MMSE ; n = 378 ) . An MMSE score of 19 was used to divide the sample into one group with lower and one with higher level of cognition . The lower MMSE group was older ( mean + /- st and ard deviation = 83.9 + /- 5.8 vs 82.2 + /- 7.5 ) and more functionally impaired ( Barthel Index , median ( interquartile range ) 11 ( 6 - 15 ) vs 17 ( 13 - 18 ) ) and had a higher risk of falling ( 64 % vs 36 % ) than the higher MMSE group . INTERVENTION A multifactorial fall prevention program comprising staff education , environmental adjustment , exercise , drug review , aids , hip protectors , and postfall problem-solving conferences . MEASUREMENTS The number of falls , time to first fall , and number of injuries were evaluated and compared by study group ( intervention vs control ) and by MMSE group . RESULTS A significant intervention effect on falls appeared in the higher MMSE group but not in the lower MMSE group ( adjusted incidence rates ratio of falls P = .016 and P = .121 and adjusted hazard ratio P < .001 and P = .420 , respectively ) . In the lower MMSE group , 10 femoral fractures were found , all of which occurred in the control group ( P = .006 ) . CONCLUSION The higher MMSE group experienced fewer falls after this multifactorial intervention program , whereas the lower MMSE group did not respond as well to the intervention , but femoral fractures were reduced in the lower MMSE group Accidents are the leading cause of death in children and a major factor in lost productive life . This case-control study investigates childhood accidents in the home by r and omly surveying children presenting to a Dublin Accident and Emergency Department . Risk factors for home accidents are examined by comparing cases ( those with accidental injuries sustained at home ) with controls . Of the 174 accident attenders , 59.2 % were boys ; 66 % of all surveyed were under 5 years . Cases were more likely to belong to Social Class 5 - 6 ( P < 0.01 ) , their fathers were less likely to be employed ( p < 0.01 ) and mothers were less likely to be working outside the home ( P < 0.01 ) . Over 50 % of injuries were due to falls ( 50.8 % ) . Blows and cuts accounted for 22.6 % of injuries , while 13 % were due to burns , 7.9 % were due to poisoning , and 5.7 % due to foreign bodies . Children under 5 were more likely than older children to have been supervised at the time of the accident . Most of the injuries were minor . However , 34 children ( 19.5 % ) required hospital admission . Measures to prevent accidents at home should be targeted towards those at most risk-parents of pre-school children and the lower social class groups . Accident prevention requires a three-pronged approach i.e. environmental change , enforcement of legislation and educational measures OBJECTIVES --To assess whether intervention by a health visitor could reduce the number of fractures , over a four year period , in those aged 70 and over . DESIGN --R and omised , controlled trial ; r and omisation by household . SETTING --General practice in a market town . SUBJECTS -- Of 863 patients aged 70 and over on the practice records , 674 were traced and successfully interviewed ; 350 were assigned to the intervention group , 324 as controls . INTERVENTION -- The people in the intervention group were allocated to the care of a health visitor . The approach was four pronged : assessment and correction of nutritional deficiencies , including reducing smoking and alcohol intake ; assessment and referral of medical conditions such as heart block or inappropriate medication ; assessment and correction of environmental hazards in the home such as poor lighting ; assessment and improvement of fitness -- for example , exercise classes for the moderately fit . The intervention continued for four years . MAIN OUTCOME MEASURE -- Fracture rate over four years . RESULTS --The incidence of fractures was 5 % ( 16/350 ) in the intervention group and 4 % ( 14/324 ) in the control group ( difference not significant ) . CONCLUSIONS --A health visitor visiting a group of people aged 70 and over and using simple preventive measures had no effect on the incidence of fractures OBJECTIVES Injury is a major US public health problem , particularly in urban minority communities . This paper evaluates the impact of the Safe Block Project , a comprehensive injury prevention trial , on home hazards and injury prevention knowledge in a poor urban African-American community . METHODS Nine census tracts in the community were allocated to either the intervention area or the control area . The intervention , carried out by trained community outreach workers , consisted of ( 1 ) home modification for simple prevention measures , ( 2 ) home inspection accompanied by information about home hazards , and ( 3 ) education about selected injury prevention practice s. Approximately 12 months after the intervention , r and om sample s of control and intervention homes were assessed for home hazards and injury prevention knowledge . RESULTS A significantly larger proportion of intervention homes than control homes had functioning smoke detectors , syrup of ipecac , safely stored medications , and reduced electrical and tripping hazards . No consistent differences were observed between control and intervention homes on home hazards requiring major effort to correct . CONCLUSIONS There was a distinct difference between control and intervention homes with respect to safety knowledge and home hazards requiring minimal to moderate effort to correct . The Safe Block Project could serve as a model for future urban injury prevention efforts OBJECTIVE To develop and evaluate an injury prevention anticipatory guidance training program for pediatric residents . DESIGN Thirty-one residents were r and omly assigned to an intervention or control group . Both groups attended a 1-hour seminar about injury prevention and the American Academy of Pediatrics TIPP ( The Injury Prevention Program ) material s. The intervention group also received 5 hours of experiential instruction on injury prevention content and counseling skills ( SAFE Counseling Framework ) . Families with infants from birth to age 6 months were enrolled in the study ( N = 196 ) ; they were followed up until the child was aged 12 to 18 months . Data were collected by means of baseline and follow-up interviews , audiotapes of medical visits , parent exit surveys , and home observations . SETTING A hospital-based continuity clinic that serves families living in low-income , inner-city neighborhoods . OUTCOMES Physician counseling and parent satisfaction , knowledge , beliefs , and behaviors . RESULTS Parents seen by physicians in the intervention group received significantly more injury prevention counseling for 5 of the 6 safety practice s , and they were significantly more satisfied with the help their physicians provided on safety topics . They were no less satisfied with their physicians ' counseling on other anticipatory guidance topics . Parents ' knowledge , beliefs , and home safety behaviors did not differ between the 2 groups . CONCLUSIONS The frequency and impact of pediatric counseling can be enhanced by experiential training that targets specific injury hazards . Because low-income families face many barriers to carrying out the recommended safety practice s , supplemental strategies are needed to ensure safer homes Pardessus V , Puisieux F , Di Pompeo C , Gaudefroy C , Thevenon A , Dewailly P : Benefits of home visits for falls and autonomy in the elderly : A r and omized trial study . Am J Phys Med Rehabil 2002;81:247–252 . Objective To investigate whether home visits by a occupational therapist reduces the risk of falling and improves the autonomy of older patients hospitalized for falling . Design In this r and omized , controlled trial set in a geriatric hospital , 60 patients ( mean age , 83.5 yr ) who were hospitalized for falling were recruited from the acute medicine department . A home visit from an occupational therapist and an ergotherapist assessed patients ’ homes for environmental hazards and recommended modifications . The outcomes measured were falls , autonomy , hospitalization for falling , institutionalization , and death . Results During the follow-up period , the rate of falls , hospitalization for falls , institutionalization , and death were not significantly different between the two groups . Both groups had a loss of dependence at 12 mo . This loss of dependence was significant in the control group but not in the intervention group . Conclusions Home visits from occupational therapists during hospitalization of older patients at risk for falling can help to preserve the patient ’s autonomy OBJECTIVES To evaluate the effect of an intervention by a multidisciplinary team to reduce falls in older people 's homes . DESIGN R and omized , controlled trial with follow-up of subjects for 1 year . SETTING University-affiliated geriatric hospital and older patients ' homes . PARTICIPANTS Three hundred sixty subjects ( mean age + /- st and ard deviation = 81.5 + /- 6.4 ) admitted from home to a geriatric hospital and showing functional decline , especially in mobility . INTERVENTION The participants were r and omly assigned to receive a comprehensive geriatric assessment followed by a diagnostic home visit and home intervention or a comprehensive geriatric assessment with recommendations and usual care at home . The home intervention included a diagnostic home visit , assessing the home for environmental hazards , advice about possible changes , offer of facilities for any necessary home modifications , and training in the use of technical and mobility aids . An additional home visit was made after 3 months to reinforce the recommendations . After 12 months of follow-up , a home visit was made to all study participants . MEASUREMENTS Number of falls , type of recommended home modifications , and compliance with recommendations . RESULTS After 1 year , there were 163 falls in the intervention group and 204 falls in the control group . The intervention group had 31 % fewer falls than the control group ( incidence rate ratio ( IRR ) = 0.69 , 95 % confidence interval ( CI ) = 0.51 - 0.97 ) . The intervention was most effective in a subgroup of participants who reported having had two or more falls during the year before recruitment into the study . In this subgroup , the proportion of frequent fallers and the rate of falls was significantly reduced for the intervention group compared with the control group ( 21 vs 36 subjects with recurrent falls , P = .009 ; IRR = 0.63 , 95 % CI = 0.43 - 0.94 ) . The compliance rate varied with the type of change recommended from 83 % to 33 % after 12 months of follow-up . CONCLUSION Home intervention based on home visits to assess the home for environmental hazards , providing information about possible changes , facilitating any necessary modifications , and training in the use of technical and mobility aids was effective in a selected group of frail older subjects with a history of recurrent falling OBJECTIVES This study was undertaken to determine whether vigorous and frail older people who identify environmental hazards in their homes have an increased risk for falls . METHODS A 1-year prospect i ve study was conducted among 266 female and 59 male community-dwelling volunteers aged 60 to 93 years who had fallen at least once during the previous year . Composite measures of home safety and of frailty were derived using principal components analysis . Participants were divided into vigorous and frail groups , and associations between baseline home safety measures and falls at home over the follow-up year were compared between the two groups . RESULTS Frail individuals were more than twice as likely as vigorous individuals to fall during follow-up ( rate ratio [ RR ] = 2.24 ; 95 % confidence interval [ CI ] = 1.54 , 3.27 ) . In the study group as a whole , falls were not strongly associated with the presence of home hazards . However , when compared with vigorous older persons living with fewer home hazards , vigorous older persons living with more home hazards were more likely to fall . The increased risk for falls among vigorous elderly was limited to falls where home hazards were present . By contrast , living with more home hazards was not associated with increased likelihood of falls among frail older persons . CONCLUSIONS While frail older persons experience higher overall fall rates , vigorous older persons should not be overlooked in fall prevention projects A r and omized trial of falls prevention program that addressed home safety , exercise , and behavioral risks was conducted with 3,182 independently living HMO members age 65 and older . The intervention decreased the odds of falling by 0.85 , but only reduced the average number of falls among those who fell by 7 % . The effect was strongest among men age 75 and older . The likelihood of avoiding falls requiring medical treatment was not significantly affected by the intervention . We conclude that the intervention dose was not of sufficient intensity or duration to have a marked protective effect on older persons . Future research should focus on more intensive intervention approaches because serious falls do not appear to be amendable to low-intensity environment/behavioral efforts OBJECTIVES Because preventing disability and falls in older adults is a national priority , a r and omized controlled trial was conducted to test a multicomponent intervention program . METHODS From a r and om sample of health maintenance organization ( HMO ) enrollees 65 years and older , 1559 ambulatory seniors were r and omized to one of three groups : a nurse assessment visit and follow-up interventions targeting risk factors for disability and falls ( group 1 , n = 635 ) ; a general health promotion nurse visit ( group 2 , n = 317 ) ; and usual care ( group 3 , n = 607 ) . Data collection consisted of a baseline and two annual follow-up surveys . RESULTS After 1 year , group 1 subjects reported a significantly lower incidence of declining functional status and a significantly lower incidence of falls than group 3 subjects . Group 2 subjects had intermediate levels of most outcomes . After 2 years of follow-up , the differences narrowed . CONCLUSIONS The results suggest that a modest , one-time prevention program appeared to confer short-term health benefits on ambulatory HMO enrollees , although benefits diminished by the second year of follow-up . The mechanisms by which the intervention may have improved outcomes require further investigation BACKGROUND Since falling is associated with serious morbidity among elderly people , we investigated whether the risk of falling could be reduced by modifying known risk factors . METHODS We studied 301 men and women living in the community who were at least 70 years of age and who had at least one of the following risk factors for falling : postural hypotension ; use of sedatives ; use of at least four prescription medications ; and impairment in arm or leg strength or range of motion , balance , ability to move safely from bed to chair or to the bathtub or toilet ( transfer skills ) , or gait . These subjects were given either a combination of adjustment in their medications , behavioral instructions , and exercise programs aim ed at modifying their risk factors ( intervention group , 153 subjects ) or usual health care plus social visits ( control group , 148 subjects ) . RESULTS During one year of follow-up , 35 percent of the intervention group fell , as compared with 47 percent of the control group ( P = 0.04 ) . The adjusted incidence-rate ratio for falling in the intervention group as compared with the control group was 0.69 ( 95 percent confidence interval , 0.52 to 0.90 ) . Among the subjects who had a particular risk factor at base line , a smaller percentage of those in the intervention group than of those in the control group still had the risk factor at the time of re assessment , as follows : at least four prescription medications , 63 percent versus 86 percent , P = 0.009 ; balance impairment , 21 percent versus 46 percent , P = 0.001 ; impairment in toilet-transfer skills , 49 percent versus 65 percent , P = 0.05 ; and gait impairment , 45 percent versus 62 percent , P = 0.07 . CONCLUSIONS The multiple-risk-factor intervention strategy result ed in a significant reduction in the risk of falling among elderly persons in the community . In addition , the proportion of persons who had the targeted risk factors for falling was reduced in the intervention group , as compared with the control group . Thus , risk-factor modification may partially explain the reduction in the risk of falling STUDY OBJECTIVE : To describe a community based programme to prevent fractures result ing from falls and evaluate the outcome in terms of changes in fracture rates and short term hospital care costs . DESIGN : Prospect i ve intervention study . SETTING : The Norwegian municipalities of Harstad ( intervention ) and Trondheim ( reference ) from 1 July 1985 to 30 June 1993 . PARTICIPANTS : The person-years of the study were estimated from yearly census data on people aged 65 years and over . There were 22970 person years in Harstad and 158911 in Trondheim . MEASUREMENTS AND MAIN RESULTS : The variables were selected and coded according to the Nordic system and the data were collected as part of a national injury surveillance system . The first three years of the study provided baseline data , while the last five years involved community based interventions -eg , the removal of environmental hazards in homes and promotion of the use of safe footwear outdoors in winter . Rates of fracture from falls did not decline in nursing homes but decreased 26.3 % in private homes ( p < 0.01 ) . In 65 - 79 year olds , there was a 48.7 % reduction in fall-fracture rates for men in traffic areas in winter ( p < 0.05 ) . The data from the reference city , Trondheim , suggested a significant rise in fractures caused by falls . There was a 16.7 % reduction in hospital admission rates of fall-fracture patients from private homes , indicating a substantial saving in short term hospital costs . The observed fall-fracture rate reductions in private homes and traffic areas suggest that major parts of the interventions were effective . CONCLUSION : Fall-fracture prophylaxis in the aged is possible in a community based setting that utilises high quality , local injury data The purpose of this research was to examine the effect of a multifactorial intervention to prevent falls by increasing self-efficacy to prevent falls , improving the knowledge of medication safety , and decreasing the number of environmental risks in older persons dwelling in the community . A sample of 120 cognitively intact residents of this community who were 65 years of age and older were recruited into a two-group pretest-post-test experimental design and r and omly assigned to an experimental group and a comparison group ( 60 in each group ) . The intervention was delivered , and data were collected during three home visits in a 4-month period . ( 1 ) Experimental subjects improved their fall self-efficacy , environmental safety , and knowledge of medication safety significantly ( p < 0.01 ) as compared with those in the comparison group at post-test ; ( 2 ) the incidence of falls was reduced at post-test in both groups compared to pretest scores , and the falling was more serious in the comparison group at post-test compared to that in the experimental group . The results can help community health professionals to individualize their interventions to the specific needs of the elderly , thus helping to prevent falls among community-dwelling elders OBJECTIVE To determine whether occupational therapist home visits targeted at environmental hazards reduce the risk of falls . DESIGN A r and omized controlled trial . SETTING Private dwellings in the community in Sydney , Australia . PARTICIPANTS A total of 530 subjects ( mean age 77 years ) , recruited primarily before discharge from selected hospital wards . INTERVENTION A home visit by an experienced occupational therapist , who assessed the home for environmental hazards and facilitated any necessary home modifications . MEASUREMENTS The primary study outcome was falls , ascertained over a 12-month follow-up period using a monthly falls calendar . RESULTS Thirty six percent of subjects in the intervention group had at least one fall during follow-up , compared with 45 % of controls ( P = .050 ) . The intervention was effective only among subjects ( n = 206 ) who reported having had one or more falls during the year before recruitment into the study ; in this group , the relative risk of at least one fall during follow-up was 0.64 ( 95 % confidence interval , 0.50 - 0.83 ) . Similar results were obtained when falls data were analyzed using survival analysis techniques ( proportional and multiplicative hazards models ) and fall rates ( mean number of falls per person per year ) . About 50 % of the recommended home modifications were in place at a 12-month follow-up visit . CONCLUSIONS Home visits by occupational therapists can prevent falls among older people who are at increased risk of falling . However , the effect may not be caused by home modifications alone . Home visits by occupational therapists may also lead to changes in behavior that enable older people to live more safely in both the home and the external environment OBJECTIVE To determine if home environmental hazards increase the risk of fall injury events among community-dwelling older persons . DESIGN Population -based case-control study . SETTING South Miami Beach , Florida . PARTICIPANTS 270 persons aged 65 years and older who sought treatment at six area hospitals for injuries result ing from falls within the dwelling unit and 691 controls , frequency matched for sex and age , selected r and omly from Health Care Financing Administration ( Medicare ) files . MAIN INDEPENDENT VARIABLES The home environment of each person , assessed directly by interviewers using a st and ardized instrument . RESULTS Environmental hazards were present in nearly all dwelling units . After adjusting for important confounding factors , most of these hazards were not associated with an increased risk of fall injury events among most older persons . Increasing numbers of tripping hazards , or total hazards in the dwelling unit , did not increase the risk of fall injury events , nor was there an increasing trend in risk . CONCLUSIONS Current fall-prevention strategies of finding and changing all environmental hazards in all community-dwelling older persons ' homes may have less potential effect than previously thought . The usefulness of grab bars , however , appears to warrant further evaluation OBJECTIVES This study estimated the effects of local pool-fencing ordinances and other factors on the rate of childhood drowning in Los Angeles County , California . METHODS Stage 1 was a retrospective dynamic cohort study of all drownings among children younger than 10 years that occurred in residential swimming pools in Los Angeles County between 1990 and 1995 . Stage 2 was a matched case-control study that compared pools in which childhood drownings occurred ( cases ) with r and omly selected pools in which drownings did not occur ( controls ) . RESULTS The drowning rate was relatively high among toddlers ( aged 1 - 4 years ) , boys , and African Americans and in areas with a high density of residential swimming pools . Pool-fencing ordinances were not associated with a reduced overall rate of childhood drowning . CONCLUSIONS Local ordinances enacted in Los Angeles County before 1996 do not appear to have been effective in reducing the rate of childhood drowning in residential pools . Possible reasons for this ineffectiveness are insufficient building codes for isolating pools from homes , inadequate enforcement of the ordinances , and inadequate operation or maintenance of fencing equipment by pool owners BACKGROUND Residential fires are the most important cause of fire-related mortality in the United States . Previous research has concentrated on fatal fires in urban areas ; considerably less is known about fatal fires in rural areas . METHODS We studied fatal and nonfatal residential fires in predominantly rural areas . Using a case-control design , we compared all 151 fatal fires ( cases ) in single-family dwellings in North Carolina during a 13-month period with a sample of nonfatal fires ( controls ) . Case fires were identified through the medical-examiner system , and control fires that occurred within a few weeks of the case fires were chosen from the records of r and omly selected fire departments statewide . For each fire , fire officials were interviewed about the dwelling , the fire , the people involved , and the fire-response system . RESULTS Although heating incidents were the leading cause of fires , fatal fires were more likely to have been caused by smoking ( 31 percent of fatal fires vs. 6 percent of nonfatal fires ) . Mobile homes posed a higher risk of death if a fire occurred ( odds ratio , 1.7 ; 95 percent confidence interval , 1.1 to 2.6 ) , as did the absence of a smoke detector ( odds ratio , 3.4 ; 95 percent confidence interval , 2.1 to 5.6 ) . Smoke detectors were more protective against death in fires involving young children and when no one present was impaired by alcohol or drugs or had a physical or mental disability . The presence of an alcohol-impaired person was the strongest independent risk factor for death in the case of a fire ( odds ratio , 7.5 ; 95 percent confidence interval , 4.4 to 12.7 ) . CONCLUSIONS Residential fires are most likely to be caused by heating equipment or smoking material s. The risk of death is greatest in fires in mobile homes , in those involving alcohol-impaired persons , and in those in houses without smoke detectors Background : Falls are a major cause of morbidity in old age . A small number of fall prevention trials in cognitively intact community-dwelling older people have been effective . This study set out to examine the preventability of falls in older people living in institutional care . Objective : To evaluate the effectiveness of falls risk factor assessment /modification and seated balance exercise training in reducing falls among elderly people living in residential care . Methods : 133 residents with a mean age of 84± ( SD ) 6.8 years were allocated at r and om by home to receive either a 6-month falls risk factor assessment /modification and seated balance exercise training programme ( n = 77 ) or 6 months of reminiscence therapy ( n = 56 ) . The risk factors targeted were postural hypotension , polypharmacy , visual acuity , and ambient lighting levels . Falls risk factor assessment s and recommendation for modifications were performed at baseline in the intervention group and assessment s repeated at 6 months . Functional reach , reaction time , timed up- and - go , grip strength , spinal flexibility , and Philadelphia Geriatric Centre Morale Scale and Mini-Mental State Examination scores were determined at baseline and at 6 months by a ‘ blind ’ observer . Falls and fractures were then monitored in both groups during a 7- to 12-month falls-monitoring follow-up period . Results : Only 90 of 133 ( 67.7 % ) residents completed the 6-month intervention period , and 84 ( 63.2 % ) completed the 7- to 12-month falls-monitoring follow-up period . Both prevalence of postural hypotension ( p = 0.0005 ) and poor visual acuity ( p = 0.04 ) were reduced in the intervention group . There was no difference between the groups in the number of falls sustained , the risk of falling [ odds ratio 0.45 ( 95 % CI 0.19–1.14 ) ] , or in the risk of recurrent falling [ odds ratio 1.07 ( 95 % CI 0.40–2.97 ) ] . No significant differences were found between the groups with regard to change in other outcome measures . Conclusions : The high drop-out rate reduced the power of this study to detect any effect of the interventions used . It is possible that either the exercises were not sufficiently vigorous or that to improve balance exercises must be performed st and ing . Further research is required to identify effective fall prevention strategies for elderly people in residential setting Objectives : Home delivery of counselling and safety devices to prevent child injuries could help parents to adopt safe behaviour . The aim of this study was to test a safety kit design ed and used in Quebec ( Canada ) . Design and subjects : One hundred families from four towns in the Paris suburbs were visited at home by nurses or doctors when their child reached 6–9 months . Selection criteria were : primipara , medical problem , psychological , and /or socioeconomic difficulties . Interventions : During the first visit , 50 families ( group 1 ) received counselling and a kit including preventive devices and pamphlets about indoor injuries and ways to avoid them . The other 50 families ( group 2 ) received counselling but not the kit . A second home visit was made 6–8 weeks later . Main outcome measures : The number of safety improvements was calculated 6–8 weeks after a first home visit . Perceived usefulness of the kit was collected from families and from interviewers . Results : Between the first and the second visits , safety improvement was significantly higher in the group with the kit . This was mainly related to the risk of fall ( p<0.02 ) , fire and burns ( p<0.001 ) , poisoning ( p<0.01 ) , and suffocation ( p<0.001 ) . For improvement related to devices provided in the kit , the difference between the groups was significant : 64.4 % improvement in group 1 versus 41.2 % in group 2 ( p<0.01 ) . The relative risk ( RR ) of safety improvement between groups was 1.56 ( 95 % confidence interval ( CI ) 1.35 to 1.80 ) . Even for improvements not related to the kit the difference remained significant : 31.2 % in group 1 versus 20.2 % in group 2 ( p<0.05 ) ; RR = 1.54 ( 95 % CI 1.22 to 1.93 ) . Conclusion : Routine home visits by social services offer a good opportunity to tackle child injury prevention . Free delivery of prevention kits and counselling allow families to modify their behaviour and homes so as to reduce risks The inclusion of counseling on home safety procedures has been recommended by the American Academy of Pediatrics as a routine part of well-child care . However , few , if any , data exist to give direction to the pediatrician interested in advising parents about home safety . In the present study , 58 couples were r and omly assigned , prospect ively , to an experimental group and a control group . Both were enrolled in a single group well-child care class that lasted 90 minutes . The control group was provided with information and discussion on nutrition , dental care , safety in the car and home , child development , child rearing , illness management , and immunizations . The experimental group received information and discussion on the same topics , and they also received specific information on burn prevention : hot water heater setting s and smoke detectors . On a subsequent home visit , 65 % of the couples in the experimental group had their hot water temperature measured at 54.4 degrees C ( 130 degrees F ) or less , whereas all of the couples in the control group had hot water temperatures of more than 54.4 degrees C ( 130 degrees F ) ( a significant difference ) . Although only one couple in the experimental group did not have an operational smoke detector , enough of the couples in the control group had operational smoke detectors that results were not significant . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To investigate the physical , social and psychological environment of families with preschool-age children to identify the most significant risk factors for unintentional injury . DESIGN A 1-year prospect i ve case-control study , using a health-visitor-administered question naire . SETTING East and Midlothian , Scotl and . SUBJECTS Seventy-nine children under 5 years of age presenting to an accident and emergency ( A&E ) department during 1998 - 1999 with an unintentional home injury and 128 matched controls . RESULTS Of 264 families , 207 responded ( 78.4 % response rate ) . The main carers of cases had a lower level of educational attainment than controls ( P<0.01 ) . This factor explained the case carer leaving fulltime education earlier , being less likely to be married and more often in receipt of government benefits . Cases lived in households with larger numbers of children , were more likely to have a physical illness , were less likely to have had a non-medically attended injury in the previous year ( P<0.01 ) but more likely to have had another A&E injury attendance . Case households had lower electrical socket cover utilization ( P<0.01 ) and fewer thought their child had adequate access to safe play areas . The main carers of cases tended to have a more negative life event experience in the preceding 6 months , but showed no significant differences in physical or mental well-being or social support . Cases seemed to be slightly more deprived members of their community . CONCLUSIONS The main carer 's educational attainment and socket cover utilization were lower in case families . These risk factors could be used to target families for injury-prevention work . Initiatives to raise educational achievement in the general population could lead to reductions in childhood injuries OBJECTIVE Our purpose was to test a four-domain predictive model of recurrent falls developed for this study . In this model , limited mobility is considered a necessary but not sufficient element in risk of recurrent falls . Three other domains , attitudinal , social , and environmental , are proposed to influence fall risk only in persons with impaired mobility . DESIGN Prospect i ve cohort study . SETTING Veterans Affairs Ambulatory Care Service serving rural and urban central North Carolina . SUBJECTS Male Veterans aged 70 or older ( n = 306 ) were monitored prospect ively for falls . At baseline , 159 screened as high-risk mobility status and 147 as low-risk mobility status . MEASUREMENTS The primary outcome was recurrent falls . The mobility screen used for risk assignment defined immobile as unable to sit without support for 60 seconds , mobile and stable as meeting criteria for normal ambulation and stair climbing , and mobile but unstable as those who met neither of the above criteria . The high-risk subjects were further assessed in their homes for mobility in more detail , attitude toward risk , social supports , and environmental status . Other data included demographics , functional status , diagnoses , and medications . RESULTS Recurrent falls occurred in 37 ( 23.3 % ) high-risk subjects and seven ( 4.8 % ) low-risk subjects ( relative risk = 4.8 , confidence interval 2.5 to 9.6 , P < 0.001 ) . Within the high-risk group , the probability of recurrent falls was significantly affected by degree of impaired mobility ( P < 0.001 ) , attitude toward risk ( P = 0.005 ) , and environment score ( P = 0.03 ) . CONCLUSIONS A simple mobility screen can identify elders at increased risk for recurrent falls . Risk within this group is further modified by risk-taking behavior and environment Tap water scald burns are an important topic of injury prevention in pediatricians ' offices . Consecutive pediatric clinic clients , r and omized to two groups , received an informational pamphlet , a one-minute discussion about tap water safety , and a baseline question naire . The first group also received a liquid-crystal thermometer for testing maximum hot tap water temperature . One month later in a follow-up telephone interview ( n = 503 ) , the impact of the added thermometer on knowledge regarding scalding , temperature testing , and thermostat lowering was assessed . Approximately 80 % of each group read the pamphlet . Reading the pamphlet was associated with greater temperature testing in the thermometer ( T ) group but not in the pamphlet only ( P ) group . Temperatures were checked by 46.4 % of the T group but by only 23.0 % of the P group ( P less than .001 ) . In the households in which the reported water temperature exceeded 54.4 degrees C ( 130 degrees F ) and the water heater was accessible , 77.3 % reported lowering the setting , independent of receiving the thermometer . The reliability of self-reported water temperature was assessed after 1 year by home visits . The use of relevant facilitating devices , such as a liquid-crystal thermometer , in-office anticipatory guidance efforts may increase behavioral compliance |
709 | 23,740,670 | Conversely , stiffness or restriction of shoulder movement was more common after conservative treatment ( data from three trials ) .
Limited evidence is available from r and omised controlled trials on the relative effectiveness of surgical versus conservative treatment for acute middle third clavicle fractures . | BACKGROUND Clavicle fractures are common , accounting for 2.6 % to 4 % of all fractures .
Eighty per cent of clavicle fractures are located in the middle third of the clavicle .
Although treatment of these fractures is usually non-surgical , displaced clavicle fractures may be considered for surgical treatment because of their greater risk of non-union .
OBJECTIVES To assess the effects ( benefits and harms ) of surgical versus conservative interventions for treating middle third clavicle fractures . | OBJECTIVES To evaluate the outcome and satisfaction of closed treatment versus open reduction and internal fixation in comminuted clavicular fractures . METHODS Sixty patients with displaced clavicular fractures were r and omized into operative ( 29 patients ) and nonoperative ( 31 patients ) groups . Three patients in the operative group did not accept the surgery , and seven patients in the nonoperative group did not complete the one-year follow-up . Outcomes were assessed using the Disability of the Arm , Shoulder and H and ( DASH ) score , Constant shoulder score , specific questions regarding patients ' final satisfaction , physical examination , measurement of the shortening of the clavicular length , and plain radiographs . RESULTS There was one nonunion in the operative group and one in the nonoperative group . The nonunion in operative group was the result of the only infection in this group . Four malunions were developed in the operative group and nineteen malunions in the nonoperative treatment , ( p<0.001 ) . Three patients in the operative group were completely dissatisfied with their treatment . Eighteen patients in the nonoperative group were partially satisfied . Pain was the main reason for dissatisfaction in this group . The mean shortening of the clavicle was 26.5 mm in the nonoperative group and 4.0 mm in the operative group . The mean DASH score for the operative and nonoperative groups were 8.6 and 21.3 , respectively ( p<0.001 ) ; and the Constant shoulder scores were 89.8 and 78.8 ( p<0.001 ) . CONCLUSION Open reduction and internal fixation of comminuted fractures of the clavicle using a reconstruction plate is an effective treatment modality . Despite the variety of complications , this method has a higher satisfaction rate than conservative treatment Background Clavicle fractures account for around 4 % of all fractures and up to 44 % of fractures of the shoulder girdle . Fractures of the middle third ( or mid-shaft ) account for approximately 80 % of all clavicle fractures . Management of this group of fractures is often challenging and the outcome can be unsatisfactory . In particular it is not clear whether surgery produces better outcomes than non-surgical management . Currently there is much variation in the use of surgery and a lack of good quality evidence to inform our decision . Methods / Design We aim to undertake a multicentre r and omised controlled trial evaluating the effectiveness and safety of conservative management versus open reduction and internal fixation for displaced mid-shaft clavicle fractures in adults . Surgical treatment will be performed using the Acumed clavicle fixation system . Conservative management will consist of immobilisation in a sling at the side in internal rotation for 6 weeks or until clinical or radiological union . We aim to recruit 300 patients . These patients will be followed-up for at least 9 months . The primary endpoint will be the rate of non-union at 3 months following treatment . Secondary endpoints will be limb function measured using the Constant-Murley Score and the Disabilities of the Arm , Shoulder and H and ( DASH ) Score at 3 and 9 months post-operatively . Discussion This article presents the protocol for a multicentre r and omised controlled trial . It gives extensive details of , and the basis for , the chosen methods , and describes the key measures taken to avoid bias and to ensure validity . Trial Registration United Kingdom Clinical Research Network ID : 8665 . The date of registration of the trial is 07/09/2006 . The date the first patient was recruited is 18/12/2007 CONTEXT The Consoli date d St and ards for Reporting of Trials ( CONSORT ) statement was developed to help improve the quality of reports of r and omized controlled trials ( RCTs ) . To date , a paucity of data exists regarding whether it has achieved this goal . OBJECTIVE To determine whether use of the CONSORT statement is associated with improvement in the quality of reports of RCTs . DESIGN AND SETTING Comparative before- and -after evaluation in which reports of RCTs published in 1994 ( pre-CONSORT ) were compared with RCT reports from the same journals published in 1998 ( post-CONSORT ) . We included 211 reports from BMJ , JAMA , and The Lancet ( journals that adopted CONSORT ) as well as The New Engl and Journal of Medicine ( a journal that did not adopt CONSORT and was used as a comparator ) . MAIN OUTCOME MEASURES Number of CONSORT items included in a report , frequency of unclear reporting of allocation concealment , and overall trial quality score based on the Jadad scale , a 5-point quality assessment instrument . RESULTS Compared with 1994 , the number of CONSORT checklist items in reports of RCTs increased in all 4 journals in 1998 , and this increase was statistically significant for the 3 adopter journals ( pre-CONSORT , 23.4 ; mean change , 3.7 ; 95 % confidence interval [ CI ] , 2.1 - 5.3 ) . The frequency of unclear reporting of allocation concealment decreased for each of the 4 journals , and this change was statistically significant for adopters ( pre-CONSORT , 61 % ; mean change , -22 % ; 95 % CI , -38 % to -6 % ) . Similarly , 3 of the 4 journals showed an improvement in the quality score for reports of RCTs , and this increase was statistically significant for adopter journals overall ( pre-CONSORT , 2.7 ; mean change , 0.4 ; 95 % CI , 0.1 - 0.8 ) . CONCLUSION Use of the CONSORT statement is associated with improvements in the quality of reports of RCTs We conducted a prospect i ve , r and omized study to determine if patients with midshaft clavicle fractures would benefit from immediate operative stabilization with a modified Hagie pin in comparison with a matched group treated with nonoperative therapy . At a level II trauma center , patients with closed midshaft clavicle fractures were prospect ively r and omized to receive either operative or nonoperative treatment . Fifty-seven ( 29 operative , 28 nonoperative ) patients were enrolled in the study . Operative patients underwent open reduction and internal fixation of the clavicle using a modified Hagie pin ; nonoperative patients were treated with a sling for comfort . All patients were followed at regular intervals for 1 year . They were evaluated for radiographic healing and complications and were scored with the Single Assessment Numeric Evaluation and L'Insalata instruments . Injury severities and radiographs were not statistically significantly different between the 2 groups . Functional scores in the operative group were slightly higher at 3 weeks , and the nonoperative group had slightly higher scores at 6 months and 1 year . The only statistically significant difference between the groups was at 3 weeks . Percentage follow-up at 1 year was 93 % for the operative group and 82 % for the nonoperative group . One patient in each group developed a nonunion , and 1 patient in each group had a refracture . Complications were higher in the operative group , and most were related to pin prominence at the posterior shoulder . Results of this study suggest that , though patients with midshaft clavicle fractures had higher functional scores at short-term follow-up after internal fixation , functional scores were similar at 6 months and 1 year . In addition , internal fixation with a modified Hagie pin was associated with a higher complication rate BACKGROUND Recent literature supports surgical intervention for shortened , displaced , mid-shaft clavicle fractures . We present the results of a r and omized clinical trial comparing locked intramedullary fixation and plate fixation for short , displaced , mid-shaft clavicle fractures . MATERIAL S AND METHODS Local ethical approval was obtained and power analysis and sample size calculations were performed prior to commencement . Patients r and omized to 2 groups to be treated with either locked intramedullary fixation or plating . Patients regularly followed up to clinical and radiographic union . The primary outcome measure was the Constant score , secondary outcome measures included the Oxford shoulder score , union rate , and complication rates . RESULTS Seventeen patients were r and omized to locked intramedullary fixation and 15 r and omized to plating . Mean age was 29.3 years . Mean follow-up was 12.4 months . There was no significant difference in either Constant scores ( P = .365 ) or Oxford scores ( P = .773 ) . There was 100 % union in both groups . In the intramedullary group , 1 case of soft tissue irritation settled after the pin removal ; 1 pin backed out and was revised . Three superficial wound infections result ed in plate removal and 8 plates ( 53 % ) were removed . DISCUSSION Intramedullary fixation has the theoretical advantage of preserving the periosteal blood supply , but carries the morbidity of pin removal . Clavicle plates are not routinely removed but require greater exposure and may compromise periosteal blood supply . CONCLUSION Both locked intramedullary fixation and plating produce good functional results ; however , metalwork may need to be removed as a second procedure BACKGROUND Time to union is a suspect measure for comparing treatments given the absence of a consensus definition of union , the limited reliability of diagnostic tests , and inconsistency in evaluation times . The purpose of this study was to quantify the variations in union and time to union according to different statistical methods and different approaches to missing data . MATERIAL S AND METHODS Data from a published multicenter , r and omized trial comparing operative and nonoperative treatment of clavicular fractures were reanalyzed . Two main types of missing data were encountered : ( 1 ) lost to follow-up or died before union and ( 2 ) missed appointment . We studied the effect of four statistical methods -comparison of means , comparison of medians , χ(2 ) , and Kaplan-Meier curves-for comparing union or time to union between cohorts for the following scenarios : strict intention-to-treat , intention-to-treat with exclusion of patients with less than 12 months of follow-up , as-treated analysis , and four different imputation methods for missing data . RESULTS Mean and median time to union varied up to 17 % , but comparative statistics consistently demonstrated shorter time to union among operatively treated patients . There were significant differences in the odds ratio , χ(2 ) values , and the number needed to treat ( 8%-62 % ) of union vs nonunion for the three principal analyses . CONCLUSION Different strategies for h and ling missed evaluations seem to influence categoric results ( eg , union or nonunion ) more than continuous measures such as time to union Objectives : To determine the cost-effectiveness of open reduction internal fixation ( ORIF ) of displaced , midshaft clavicle fractures in adults . Design : Formal cost-effectiveness analysis based on a prospect i ve , r and omized , controlled trial . Setting : Eight hospitals in Canada ( seven university-affiliated and one community hospital ) . Patients / Participants : One hundred thirty-two adults with acute , completely displaced , midshaft clavicle fractures . Intervention : Clavicle ORIF versus nonoperative treatment . Main Outcome Measurements : Utilities derived from SF-6D . Results : The base case cost per quality -adjusted life-year ( QALY ) gained for ORIF was $ 65,000 . Cost-effectiveness improved to $ 28,150/QALY gained when the functional benefit from ORIF was assumed to be permanent with cost per QALY gained falling below $ 50,000 when the functional advantage persisted for 9.3 years or more . In other sensitivity analyses , the cost per QALY gained for ORIF fell below $ 50,000 when ORIF cost less than $ 10,465 ( base case cost $ 13,668 ) or the long-term utility difference between nonoperative treatment and ORIF was greater than 0.034 ( base case difference 0.014 ) . Short-term disutility associated with fracture healing also affected cost-effectiveness with the cost per QALY gained for ORIF falling below $ 50,000 when the utility of a fracture treated nonoperatively before union was less than 0.617 ( base case utility 0.706 ) or when nonoperative treatment increased the time to union by 20 weeks ( base case difference 12 weeks ) . Conclusions : The cost-effectiveness of ORIF after acute clavicle fracture depended on the durability of functional advantage for ORIF compared with nonoperative treatment . When functional benefits persisted for more than 9 years , ORIF had a favorable value compared with many accepted health interventions Background The traditional view that the vast majority of midshaft clavicular fractures heal with good functional outcomes following non-operative treatment may be no longer valid for all midshaft clavicular fractures . Recent studies have presented a relatively high incidence of non-union and identified speciic limitations of the shoulder function in subgroups of patients with these injuries . Aim A prospect i ve , multicentre r and omised controlled trial ( RCT ) will be conducted in 21 hospitals in the Netherl and s , comparing fracture consolidation and shoulder function after either non-operative treatment with a sling or a plate fixation . Methods / design A total of 350 patients will be included , between 18 and 60 years of age , with a dislocated midshaft clavicular fracture . The primary outcome is the incidence of non-union , which will be determined with st and ardised X-rays ( Antero-Posterior and 30 degrees caudocephalad view ) . Secondary outcome will be the functional outcome , measured using the Constant Score . Strength of the shoulder muscles will be measured with a h and held dynamometer ( MicroFET2 ) . Furthermore , the health-related Quality of Life score ( ShortForm-36 ) and the Disabilities of Arm , Shoulder and H and ( DASH ) Outcome Measure will be monitored as subjective parameters . Data on complications , bone union , cosmetic aspects and use of painkillers will be collected with follow-up question naires . The follow-up time will be two years . All patients will be monitored at regular intervals over the subsequent twelve months ( two and six weeks , three months and one year ) . After two years an interview by telephone and a written survey will be performed to evaluate the two-year functional and mechanical outcomes . All data will be analysed on an intention-to-treat basis , using univariate and multivariate analyses . Discussion This trial will provide level-1 evidence for the comparison of consolidation and functional outcome between two st and ardised treatment options for dislocated midshaft clavicular fractures . The gathered data may support the development of a clinical guideline for treatment of clavicular fractures . Trial registration Netherl and s National Trial Register INTRODUCTION Elastic stable intramedullary nailing ( ESIN ) of displaced mid-shaft clavicular fractures is a minimally invasive technique which was reported to be an easy procedure with low complication rates , good cosmetic and functional results , restoration of clavicular length and fast return to daily activities . Recent studies , however , also report on higher complication rates and specific problems with the use of this technique . This prospect i ve study compares ESIN with non-operative treatment of displaced mid-shaft clavicular fractures . METHODS Between December 2003 and August 2007 , 120 patients volunteered to participate . Of these , 112 patients completed the study ( 60 in the operative and 52 in the non-operative group ) . Patients in the non-operative group were treated with a simple shoulder sling . In the operative group , intramedullary stabilisation was performed within 3 days of the trauma . Clavicular shortening was determined after trauma and after osseous consolidation on thorax posteroanterior radiographs as the proportional length difference between the left and right side with the uninjured side serving as a control for clavicular length ( 100 % ) . Radiographic union was assessed every 4 weeks on 20 degrees cephalad anteroposterior and posteroanterior radiographs of the clavicle . Constant shoulder scores and DASH scores ( DASH , disabilities of the arm , shoulder and h and ) were assessed at final follow-up after 2 years . RESULTS ESIN led to faster osseous healing and better restoration of clavicular length in simple fractures . We were not able to restore clavicular length in comminuted fractures using ESIN . Functional outcome at a mean follow-up of 24 months ( range : 22 - 27 months ) was better in the operative group . Delayed union and non-union accounted for the majority of complications in the non-operative group . In the operative group , telescoping was the main complication , which occurred in complex fractures with severe post-traumatic shortening only . CONCLUSION We recommend ESIN for all simple displaced mid-shaft clavicular fractures in order to minimise the rate of delayed union , non-union and symptomatic mal-union . We also recommend ESIN in comminuted fractures with moderate ( < or = 7 % ) post-traumatic shortening , as they will heal with moderate shortening . In comminuted fractures with severe shortening , however , we recommend plate osteo synthesis in order to provide for stability , clavicular length and endosteal blood supply BACKGROUND Clavicle fractures are common and usually heal without complications . In this study , we evaluated the outcomes of non-operative versus operative management of displaced fractures . METHODS In a prospect i ve clinical trial study , sixty-five patients with displaced clavicle mid-shaft fractures were non-r and omly divided in two treatment groups . The first group underwent non-operative treatment with figure of 8 b and age ( 30 patients ) , and the other underwent operative treatment with plate fixation ( 35 patients ) . Figure of 8 b and age and 3.5 millimeter DCP plate with at least six cortical screws were used in non-operative and operative groups respectively . We followed up all patients at weeks 2 , 6 and 12 , and at month sixth . In addition to clinical examination and x-ray evaluation , we assessed satisfaction , DASH and Constant Shoulder Score for each individual . RESULTS The average duration s of union were 19.3 and 24.4 weeks in operative and non-operative groups respectively ( P=0.006 ) . Satisfaction with operative treatment was 74.3 % and with non-operative treatment was 66.7 % , showing no significant difference ( P=0.500 ) . The non-union rate was 5.7 % in the operative group and 13.3 % in the non-operative group ( P=0.518 ) . A significant difference between the two groups in terms of DASH and Constant Shoulder Scores after the six-month follow-up was not found ( P=0.352 ) . CONCLUSIONS According to our results , we recommend operative treatment in mid-shaft clavicle fractures only when there is a definitive indication Objectives : To compare results of primary internal fixation of acute displaced midshaft clavicle fractures with those managed nonoperatively in terms of fracture union and functional outcome . Design : Prospect i ve cohort study . Setting : Level II military trauma center . Patients / Participants : Seventy-three patients ( civilian and military ) between 20 and 50 years of age with displaced midshaft clavicle fractures were allocated either to the operative ( n = 45 ) or nonoperative ( n = 28 ) group . Intervention : Patients in the nonoperative group were managed by simple sling immobilization , whereas in the operative group , fractures were reduced and fixed with a contoured reconstruction plate . Main Outcome Measurements : The patients were actively followed up during an 18-month period . Primary outcome measures were the rates of nonunion and symptomatic malunion ; secondary outcomes included the assessment of the Constant score and the overall local complication rate . Results : The 18-month follow-up rate was 90 % . All fractures in the operative group united compared with eight nonunions ( 29 % ) in the nonoperative group ( P = 0.002 ) . Ten symptomatic malunions ( 36 % ) occurred in the nonoperative group , whereas only two ( 4 % ) were reported for the operative group ( P = 0.0008 ) . Constant shoulder scores were significantly better for the operative group at all follow-ups ( P < 0.0001 ) . All six operative complications were implant-related . Conclusions : In this prospect i ve cohort study , primary open reduction and internal plate fixation of acute displaced midshaft clavicular fractures result ed in improved outcomes and a decreased rate of nonunion and symptomatic malunion compared with nonoperative treatment Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field Seventy-nine out- patients with midclavicular fractures were included in a prospect i ve , r and omized trial comparing treatment with a figure-of-eight b and age and a simple sling . Sixty-one patients completed the study and were reevaluated clinical ly and radiographically after 3 months . We found that treatment with a simple sling caused less discomfort and perhaps fewer complications than with the figure-of-eight b and age . The functional and cosmetic results of the two methods of treatment were identical and alignment of the healed fractures was unchanged from the initial displacement BACKGROUND Few r and omized controlled trials have compared operative with nonoperative treatment of clavicular fractures . METHODS Patients with displaced midshaft clavicular fractures were r and omized either to nonoperative treatment with a sling or to operative treatment with a stainless steel 3.5-mm reconstruction plate . Outcome measures were the Constant shoulder score , DASH ( Disabilities of the Arm , Shoulder and H and ) score , pain , fracture-healing , and complications . The null hypothesis was that the Constant and DASH scores would not differ between the groups at the one-year follow-up evaluation . RESULTS In accordance with the power analysis , we included sixty patients in the study ; thirty-two were r and omized to the nonoperative group and twenty-eight to the operative group . We found no difference in the Constant score ( p = 0.75 ) , the DASH score ( p = 0.89 ) , or pain ( p = 0.98 ) between the groups at the one-year follow-up evaluation . All fractures in the operative group healed , but six nonunions ( 24 % ) occurred in the nonoperative group . CONCLUSIONS One year after a displaced midshaft clavicular fracture , nonoperative treatment result ed in a higher nonunion rate but similar function and disability compared with operative treatment A self-administered question naire was design ed to assess the severity of symptoms related to and the functional status of the shoulder . It includes domains of global assessment , pain , daily activities , recreational and athletic activities , work , satisfaction , and areas for improvement . Each domain is grade d separately and is weighted to arrive at the total score . The over-all scale and each domain were prospect ively tested for validity , reliability , and responsiveness to clinical change . One hundred patients who were seen for evaluation of the shoulder were enrolled in the study . The validity of the scale was demonstrated by moderate-to-high correlation of the domains and individual questions of the Shoulder Rating Question naire with those of the Arthritis Impact Measurement Scales 2 . Validity was supported further by significant correlation of the scores in each domain with the level of satisfaction in that domain and by significantly lower scores in domains that patients selected as areas important for improvement . The over-all scale and each domain were internally consistent ( Cronbach alpha , 0.71 to 0.90 ) . Reproducibility was evaluated by repeated administration of the question naire after a mean of three days to forty patients whose condition was clinical ly stable . Reproducibility of the over-all question naire and individual domains was excellent ( Spearman-Brown index , 0.94 to 0.98 ) . Individual questions were reproducible , with a weighted kappa value of more than 0.7 for each . Responsiveness was evaluated by comparison of the preoperative and postoperative scores of thirty patients who had a satisfactory result one year after an operation on the shoulder . The over-all Shoulder Rating Question naire and each domain were responsive to clinical change as demonstrated by favorable st and ardized response means ( range , 1.1 to 1.9 ) and indices of responsiveness ( range , 1.1 to 2.0 ) . Similar analysis performed for individual diagnostic groups supported the validity , reliability , and responsiveness of the question naire in each group . The self-administered shoulder question naire was found to be valid , reliable , and responsive to clinical change . These qualities should make it a useful instrument for the prospect i ve assessment of the outcome of treatment of disorders related to the shoulder Objective : To compare elastic stable intramedullary nailing ( ESIN ) with nonoperative treatment of fully displaced midshaft clavicular fractures in adults . Design : The study was a r and omized , controlled , clinical trial . Setting : Level 1 trauma center . Patients and Methods : Sixty patients between 18 and 65 years of age participated and completed the study . They were r and omized to either operative or nonoperative treatment with a 2-year follow-up . Intervention : Thirty patients were treated with a simple shoulder sling and 30 patients with ESIN within 3 days after trauma . Main Outcome Measurement : Complications after operative and nonoperative treatments , Disabilities of the Arm , Shoulder and H and ( DASH ) score and Constant Shoulder Score for outcome measurement , and clavicular shortening . Results : Fracture union was achieved in all patients in the operative group , whereas nonunion was observed in 3 of 30 patients of the nonoperative group . Two symptomatic malunions required corrective osteotomy in the nonoperative group . Medial nail protrusion occurred in 7 cases in the operative group . Implant failure with revision surgery was necessary in 2 patients after an additional adequate trauma . DASH scores were lower in the operative group throughout the first 6 months and 2 years after trauma , with a significant difference during the first 18 weeks . Constant scores were significantly higher after 6 months and 2 years after intramedullary stabilization . Patients in the operative group showed a significant improvement of posttraumatic clavicular shortening ; they were also more satisfied with cosmetic appearance and overall outcome . Conclusions : ESIN of displaced midshaft clavicular fractures result ed in a lower rate of nonunion and delayed union , a faster return to daily activities , and a better functional outcome . Clavicular shortening was significantly lower , and overall satisfaction was higher in the operative group OBJECTIVES The aim of this prospect i ve study was to compare the results achieved in two groups of patients treated for mid-clavicular fracture . METHODS The first group of 27 patients was treated nonoperatively with a rucksack b and age , whereas the second group underwent intramedullary fixation with a titanium pin , using a minimally invasive technique . Within the follow-up period of 6 months , results were evaluated seven times . RESULTS During the whole period significantly ( p<0.05 ) better results were observed in the group of operated patients concerning shoulder function , Constant score , DASH score , personal satisfaction , pain , and cosmetic result . In the second group return to work occurred in less than half the time of the first group . CONCLUSION Intramedullary nailing of mid-clavicular fractures is a safe and minimally invasive operation technique . Early functional and cosmetic results are not worse than results after nonoperative treatment with a rucksack b and age AIM In Germany , non-operative treatment using a figure of eight dressing is the most common method for managing fractures of the mid-third of the clavicle . This treatment is chosen preferably even in cases of dislocated fractures . The described procedures of open osteo synthesis are characterised by a huge access trauma . Up to date literature shows the advantages of intramedullary pin osteo synthesis , which can be considered as a minimally invasive procedure . In this study we compare the results of pin-osteo synthesis with the non-operative treatment in athletes . METHODS This prospect i ve r and omised trial compares the results of 68 athletes with an isolated fracture of the middle third of the clavicle . One group ( n=35 ) received intramedullary splints , the other group ( n=33 ) had a figure of eight dressing instead . RESULTS Post-traumatic pain was significantly ( p=0.05 ) lower in the group that had intramedullary splints . Furthermore , the postoperative mobility of the injured area was significantly better ( p=0.05 ) . Measurements of the strength of the injured side 120 days after the trauma show a significant ( p=0.01 ) advantage of the pin osteo synthesis . CONCLUSION The intramedullary titanium pin osteo synthesis is a promising alternative with better results . Up to date literature and our own results prove the advantages of this minimally invasive osteo synthesis . This procedure allows sports activities to be resumed soon after the operation . As intramedullary pin osteo synthesis is an ideal operation of fractures of the middle third of the clavicle , this comparatively easy procedure with few complications should be more widespread Background Based on short-term ( 1 year or less ) followup , primary fixation of displaced midshaft clavicle fractures reportedly results in better function compared with that reported for nonoperative methods . Whether better function persists beyond 1 year is unclear . Questions / purpose sFor displaced midshaft clavicle fractures , do the better mean Disabilities of the Arm , Shoulder and H and ( DASH ) and Constant-Murley Shoulder ( CSS ) scores for operative versus nonoperative treatment at 1 year change between 1- and 2-year followup ? Patients and Methods We previously reported 132 patients in a r and omized prospect i ve trial at 1 year , and here we report a further followup of 95 of the 132 patients ( 72 % ) at 2 years after injury . We evaluated all patients with the DASH and CSS scores . Results The mean DASH and CSS scores were similar at 2 years compared with 1 year postinjury for both the nonoperated and operated patients . The mean scores for the operated patients remained higher than those in the nonoperative group ( DASH operative 4.1 ± 7.0 versus DASH nonoperative 11.4 ± 19.7 , CSS operative 97.1 ± 4.5 versus CSS nonoperative 91.6 ± 14.1 ) at 2 years postinjury . Conclusions The improvement in DASH and CSS scores seen with primary fixation of displaced clavicle fractures persists at 2 years but does not differ from values seen after 1 year of followup , suggesting a clinical steady state has been reached whereby outcome is unlikely to change with time . Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence BACKGROUND There is a growing trend to treat displaced midshaft clavicular fractures with primary open reduction and plate fixation ; whether such treatment results in improved patient outcomes is debatable . The aim of this multicenter , single-blinded , r and omized controlled trial was to compare union rates , functional outcomes , and economic costs for displaced midshaft clavicular fractures that were treated with either primary open reduction and plate fixation or nonoperative treatment . METHODS In a prospect i ve , multicenter , stratified , r and omized controlled trial , 200 patients between sixteen and sixty years of age who had an acute displaced midshaft clavicular fracture were r and omized to receive either primary open reduction and plate fixation or nonoperative treatment . Functional assessment was conducted at six weeks , three months , six months , and one year with use of the Disabilities of the Arm , Shoulder and H and ( DASH ) and Constant scores . Union was evaluated with use of three-dimensional computed tomography . Complications were recorded , and an economic evaluation was performed . RESULTS The rate of nonunion was significantly reduced after open reduction and plate fixation ( one nonunion ) as compared with nonoperative treatment ( sixteen nonunions ) ( relative risk = 0.07 ; p = 0.007 ) . Group allocation to nonoperative treatment was independently predictive of the development of nonunion ( p = 0.0001 ) . Overall , DASH and Constant scores were significantly better after open reduction and plate fixation than after nonoperative treatment at the time of the one-year follow-up ( DASH score , 3.4 versus 6.1 [ p = 0.04 ] ; Constant score , 92.0 versus 87.8 [ p = 0.01 ] ) . However , when patients with nonunion were excluded from analysis , there were no significant differences in the Constant scores or DASH scores at any time point . Patients were less dissatisfied with symptoms of shoulder droop , local bump at the fracture site , and shoulder asymmetry in the open reduction and plate fixation group ( p < 0.0001 ) . The cost of treatment was significantly greater after open reduction and plate fixation ( p < 0.0001 ) . CONCLUSIONS Open reduction and plate fixation reduces the rate of nonunion after acute displaced midshaft clavicular fracture compared with nonoperative treatment and is associated with better functional outcomes . However , the improved outcomes appear to result from the prevention of nonunion by open reduction and plate fixation . Open reduction and plate fixation is more expensive and is associated with implant-related complications that are not seen in association with nonoperative treatment . The results of the present study do not support routine primary open reduction and plate fixation for the treatment of displaced midshaft clavicular fractures BACKGROUND Recent studies have shown a high prevalence of symptomatic malunion and nonunion after nonoperative treatment of displaced midshaft clavicular fractures . We sought to compare patient-oriented outcome and complication rates following nonoperative treatment and those after plate fixation of displaced midshaft clavicular fractures . METHODS In a multicenter , prospect i ve clinical trial , 132 patients with a displaced midshaft fracture of the clavicle were r and omized ( by sealed envelope ) to either operative treatment with plate fixation ( sixty-seven patients ) or nonoperative treatment with a sling ( sixty-five patients ) . Outcome analysis included st and ard clinical follow-up and the Constant shoulder score , the Disabilities of the Arm , Shoulder and H and ( DASH ) score , and plain radiographs . One hundred and eleven patients ( sixty-two managed operatively and forty-nine managed nonoperatively ) completed one year of follow-up . There were no differences between the two groups with respect to patient demographics , mechanism of injury , associated injuries , Injury Severity Score , or fracture pattern . RESULTS Constant shoulder scores and DASH scores were significantly improved in the operative fixation group at all time-points ( p = 0.001 and p < 0.01 , respectively ) . The mean time to radiographic union was 28.4 weeks in the nonoperative group compared with 16.4 weeks in the operative group ( p = 0.001 ) . There were two nonunions in the operative group compared with seven in the nonoperative group ( p = 0.042 ) . Symptomatic malunion developed in nine patients in the nonoperative group and in none in the operative group ( p = 0.001 ) . Most complications in the operative group were hardware-related ( five patients had local irritation and /or prominence of the hardware , three had a wound infection , and one had mechanical failure ) . At one year after the injury , the patients in the operative group were more likely to be satisfied with the appearance of the shoulder ( p = 0.001 ) and with the shoulder in general ( p = 0.002 ) than were those in the nonoperative group . CONCLUSIONS Operative fixation of a displaced fracture of the clavicular shaft results in improved functional outcome and a lower rate of malunion and nonunion compared with nonoperative treatment at one year of follow-up . Hardware removal remains the most common reason for repeat intervention in the operative group . This study supports primary plate fixation of completely displaced midshaft clavicular fractures in active adult patients This prospect i ve consecutive case series was done to evaluate indications , technical pitfalls and functional outcome of elastic stable intramedullary nailing of displaced midclavicular fractures in 14 athletes . Constant score and radiographs were evaluated after 1 and 6 weeks , 3 months and 6 months in 13 patients . Mean age was 28 years . The average follow-up was 17 months . Mean operation time was 62 minutes . Open reduction through an additional small incision was necessary for 7 fractures . Mean hospital stay was 1.2 days . Secondary fracture displacement was observed in 1 patient . The Constant score averaged 81 after 1 week , 96 after 6 weeks and 98 after 6 months . Compared to the contralateral side , average shortening of the clavicle was 1.7 mm . Overall , elastic stable intramedullary nailing provided good restoration of the length of the clavicle and allowed immediate active mobilisation with early return to normal activity . Functional results were excellent OBJECTIVE Studies showed elastic stable intramedullary nailing ( ESIN ) of displaced midclavicular fractures has excellent outcomes , as well as high complication rates and specific problems . The aim was to discuss ESIN of midshaft clavicular fractures . METHODS Totally 60 eligible patients ( aged 18 - 63 years ) were r and omized to either ESIN group or non-operative group between January 2007 and May 2008 . Clavicular shortening was measured after trauma and osseous consolidation . Radiographic union and complications were assessed . Function analysis including Constant shoulder scores and disabilities of the arm , shoulder and h and ( DASH ) scores were performed after a 15-month follow-up . RESULTS ESIN led to a signifcantly shorter time to union , especially for simple fractures . In ESIN group , all patients got fracture union , of which 5 cases had medial skin irritation and 1 patient needed revision surgery because of implant failure . In the nonoperative group , there were 3 nonunion cases and 2 symptomatic malunions developed requiring corrective osteotomy . At 15 months after intramedullary stabilization , patients in the ESIN group were more satisfied with the appearance of the shoulder and overall outcome , and they benefited a lot from the great improvement of post-traumatic clavicular shortening . Furthermore , DASH scores were lower and Constant scores were significantly higher in contrast to the non-operative group . CONCLUSION ESIN is a safe minimally invasive surgical technique with lower complication rate , faster return to daily activities , excellent cosmetic and better functional results , restoration of clavicular length for treating mid-shaft clavicular fractures , result ing in high overall satisfaction , which can be regard as an alternative to plate fixation or nonoperative treatment of mid-shaft clavicular fractures BACKGROUND Nonunion is a rare complication of a fracture of the clavicle , but its occurrence can compromise shoulder function . The aim of this study was to evaluate the prevalence of and risk factors for nonunion in a cohort of patients who were treated nonoperatively after a clavicular fracture . METHODS Over a fifty-one-month period , we performed a prospect i ve , observational cohort study of a consecutive series of 868 patients ( 638 men and 230 women with a median age of 29.5 years ; interquartile range , 19.25 to 46.75 years ) with a radiographically confirmed fracture of the clavicle , which was treated nonoperatively . Eight patients were excluded from the study , as they received immediate surgery . Patients were evaluated clinical ly and radiographically at six , twelve , and twenty-four weeks after the injury . There were 581 fractures in the diaphysis , 263 fractures in the lateral fifth of the clavicle , and twenty-four fractures in the medial fifth . RESULTS On survivorship analysis , the overall prevalence of nonunion at twenty-four weeks after the fracture was 6.2 % , with 8.3 % of the medial end fractures , 4.5 % of the diaphyseal fractures , and 11.5 % of the lateral end fractures remaining ununited . Following a diaphyseal fracture , the risk of nonunion was significantly increased by advancing age , female gender , displacement of the fracture , and the presence of comminution ( p < 0.05 for all ) . On multivariate analysis , all of these factors remained independently predictive of nonunion , and , in the final model , the risk of nonunion was increased by lack of cortical apposition ( relative risk = 0.43 ; 95 % confidence interval = 0.34 to 0.54 ) , female gender ( relative risk = 0.70 ; 95 % confidence interval = 0.55 to 0.89 ) , the presence of comminution ( relative risk = 0.69 ; 95 % confidence interval = 0.52 to 0.91 ) , and advancing age ( relative risk = 0.99 ; 95 % confidence interval = 0.99 to 1.00 ) . Following a lateral end fracture , the risk of nonunion was significantly increased only by advancing age and displacement of the fracture ( p < 0.05 for both ) . On multivariate analysis , both of these factors remained independently predictive of nonunion ( p < 0.05 ) , and , in the final model , the risk of nonunion was increased by a lack of cortical apposition ( relative risk = 0.38 ; 95 % confidence interval = 0.25 to 0.57 ) and advancing age ( relative risk = 0.98 ; 95 % confidence interval = 0.97 to 0.99 ) . CONCLUSIONS Nonunion at twenty-four weeks after a clavicular fracture is an uncommon occurrence , although the prevalence is higher than previously reported . There are subgroups of individuals who appear to be predisposed to the development of this complication , either from intrinsic factors , such as age or gender , or from the type of injury sustained . The predictive models that we developed may be used clinical ly to counsel patients about the risk for the development of this complication immediately after the injury OBJECTIVE To discuss the concepts of the minimal clinical ly important difference ( MCID ) and the smallest detectable difference ( SDD ) and to examine their relation to required sample sizes for future studies using concrete data of the condition-specific Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and the generic Medical Outcomes Study 36-Item Short Form ( SF-36 ) in patients with osteoarthritis of the lower extremities undergoing a comprehensive inpatient rehabilitation intervention . METHODS SDD and MCID were determined in a prospect i ve study of 122 patients before a comprehensive inpatient rehabilitation intervention and at the 3-month followup . MCID was assessed by the transition method . Required SDD and sample sizes were determined by applying normal approximation and taking into account the calculation of power . RESULTS In the WOMAC sections the SDD and MCID ranged from 0.51 to 1.33 points ( scale 0 to 10 ) , and in the SF-36 sections the SDD and MCID ranged from 2.0 to 7.8 points ( scale 0 to 100 ) . Both question naires showed 2 moderately responsive sections that led to required sample sizes of 40 to 325 per treatment arm for a clinical study with unpaired data or total for paired followup data . CONCLUSION In rehabilitation intervention , effects larger than 12 % of baseline score ( 6 % of maximal score ) can be attained and detected as MCID by the transition method in both the WOMAC and the SF-36 . Effects of this size lead to reasonable sample sizes for future studies lying below n = 300 . The same holds true for moderately responsive question naire sections with effect sizes higher than 0.25 . When design ing studies , assumed effects below the MCID may be detectable but are clinical ly meaningless BACKGROUND The minimal clinical ly important difference ( MCID ) is increasingly used to evaluate treatment effectiveness . The MCID for the Constant score has not been previously reported . MATERIAL S AND METHODS A prospect ively collected cohort of 802 consecutive shoulders with arthroscopically treated partial- or full-thickness rotator cuff tears was analyzed . The Constant score was measured preoperatively and at 3 months and 1 year postoperatively . At follow-up visits , the patients were asked a simple 2-stage question : Is the shoulder better or worse after the operation compared with the preoperative state ? This single 2-level question was used as an indicator of patient satisfaction and as an anchor to calculate the MCID for the Constant score . RESULTS At 1 year , 781 ( 97.4 % ) patients ( 474 men , 307 women ) were available for follow-up . The preoperative Constant score was 53.1 ( SD 17.2 ) in all patients , 56.2 ( SD 17.4 ) in male patients , and 48.2 ( SD 15.6 ) in female patients . Postoperatively at 3 months , the scores were 61.7 ( SD 16.4 ) in all patients , 65.1 ( SD 16.1 ) in male patients , and 56.8 ( SD 15.5 ) in female patients . At 1 year , the scores were 75.9 ( SD 15.2 ) in all patients , 79.0 ( SD 14.9 ) in male patients , and 71.0 ( SD 14.3 ) in female patients . At 3 months postoperatively , 92.2 % of male patients and 87.2 % of female patients were satisfied with the outcome ( P = .027 ) ; at 1 year , the satisfaction was 93.2 % and 89.5 % , respectively ( P = .067 ) . Five different statistical approaches yielded 5 different MCID estimates ( range , 2 - 16 ) . The 3-month mean change estimate of MCID was 10.4 points . CONCLUSION Our study demonstrates an MCID estimate of 10.4 points as the threshold for the Constant score in patients with rotator cuff tear . LEVEL OF EVIDENCE Basic science study , validation of outcomes instruments/classification systems In a prospect i ve study , the age- and gender-specific incidence and features of clavicular fractures were studied during 1989 and 1990 . The population at risk consisted of about 200,000 individuals aged 15 or above in the county of Uppsala , Sweden . There were 187 clavicular fractures in 185 patients corresponding to an annual incidence of 50/100,000 ( males 71/100,000 , women 30/100,000 ) . Males were significantly younger and sustained comminuted fractures more often than women . The fracture incidence decreased with age in both genders , although the reduction was significant only in men . Bicycle accidents most frequently caused clavicular fractures in both genders , whereas sports activities were significantly more common in men . Right and left clavicles were almost as frequently fractured , and a direct fall on the shoulder was the most frequent mechanism of injury for both genders . There was no difference between genders in the anatomical location with about three of four fractures occurring through the middle part and one of four through the acromial part of the clavicle . Ninety-five percent healed uneventfully , while non-union developed in 5 % - evenly distributed between the middle part of the clavicle and the acromial part |
710 | 26,747,131 | Conclusion : Our findings suggest that erythropoietin levels in AUE , although elevated , remain inappropriately low , particularly when compared with other forms of anemia .
This suggests a relative erythropoietin deficiency or a blunted erythroid cell response | Introduction : We conducted a systematic review and meta- analysis of observational studies in order to explore the relationship between erythropoietin ( EPO ) and hemoglobin in elderly individuals with anemia of unknown etiology ( AUE ) and other forms of anemia . | OBJECTIVES To characterize anemia in elderly nursing home residents . DESIGN Prospect i ve multiinstitutional cohort study . SETTING Five nursing homes . PARTICIPANTS From retrospective analysis , residents found to be anemic using chart review were prospect ively r and omized . Of the 81 residents enrolled , 60 were anemic . MEASUREMENTS Chart review for medical history and factors related to treatment or history of anemia , extensive laboratory evaluation for causes of anemia , and classification of anemia by two hematologists . RESULTS Among the 60 anemic residents , the causes of anemia were idiopathic ( n=27 ) , iron-deficiency ( n=14 ) , anemia associated with chronic disease ( n=8 ) , anemia of renal insufficiency ( n=6 ) , and other ( n=5 ) . The eryrthropoietin ( EPO ) response to anemia was lower in residents with idiopathic anemia ( IA ) than in those with iron-deficiency anemia , and this correlated with renal function as estimated using calculated creatinine clearance . In this elderly population , advancing age was not correlated with lower EPO response . CONCLUSION IA is common in nursing home residents . A lower EPO response contributes to the high prevalence of anemia in this setting and may be due , in part , to occult renal dysfunction BACKGROUND To accurately determine the causes of anemia and proportion of unexplained anemia in a racially diverse cohort of older adults after a comprehensive and st and ardized evaluation . METHODS We evaluated results from a single-institutional university anemia clinic . Patients with anemia , defined as a hemoglobin less than 13.0 g/dL for men and less than 12.0 g/dL for women , underwent a prospect i ve st and ardized history , physical examination , and laboratory measures , with additional studies including bone marrow examination as indicated . Empiric treatment trials were given for identified deficiencies . RESULTS One hundred and seventy-four primarily community-dwelling adults aged 65 years and older were evaluable . African Americans accounted for 69 % of patients and whites were 27 % . Anemia etiologies included iron deficiency anemia at 25.3 % , anemia of chronic inflammation at 9.8 % , and hematologic malignancy in 7.5 % . Unexplained anemia in the elderly accounted for 43.7 % and predominated in both African Americans and whites . The prevalence of iron deficiency anemia and hematologic malignancies did not differ by race . Unexplained anemia in the elderly showed a consistent phenotype composed of a hypoproliferative mild-to-moderate anemia with suppressed serum erythropoietin . Specifically , erythropoietin levels showed no correlation with hemoglobin concentration in unexplained anemia in the elderly ( r = -.15 , p = .19 ) as opposed to iron deficiency anemia ( r = -.63 , p < .0001 ) . CONCLUSIONS In summary , an intensive hematologic evaluation reveals a wide number of anemia etiologies among older adults , including 7.5 % with hematologic malignancies ; nevertheless , unexplained anemia in the elderly prevails as the most common category in whites and African Americans BACKGROUND In the older population , anemia has been associated with poor outcomes including disability and mortality . Underst and ing the mechanisms leading to anemia is essential to plan better treatment and prevention strategies . We tested the hypothesis that the age-related decline in kidney function is associated with an increased prevalence of anemia and that such an increase is accompanied by a concomitant decrement in erythropoietin levels . METHODS Data were from the InCHIANTI study , a population -based study performed in a sample of community-dwelling older ( > or = 65 years ) persons living in Italy . This analysis included 1005 participants with complete data on hemoglobin and erythropoietin levels and markers of renal function . RESULTS The prevalence of anemia according to the World Health Organization criteria ( hemoglobin level < 12 g/dL for women and < 13 g/dL for men ) was 12.0 % and increased with age in both sexes . After adjusting for age , diseases , and other confounders , only participants with a creatinine clearance ( CrCl ) of 30 mL/min or lower ( < or = 0.50 mL/s ) had a higher prevalence of anemia compared with those with a CrCl higher than 90 mL/min ( > 1.50 mL/s ) ( P<.01 ) . Consistently , participants with a CrCl of 30 mL/min or lower ( < or = 0.50 mL/s ) had significantly lower age- and hemoglobin-adjusted erythropoietin endogenous levels . After excluding men and women with CrCl of 30 mL/min or lower ( < or = 0.50 mL/s ) and adjusting for confounders , we found a trend toward an increase in prevalence of anemia with decreasing renal function ; however , it was not statistically significant . CONCLUSIONS Severe age-related decline in renal function is associated with a reduced erythropoietin secretion and anemia . Whether moderate kidney impairment in older persons is associated with a progressively increasing risk of anemia remains to be determined The reasons for inadequate production of erythropoietin ( EPO ) in patients with ESRD are poorly understood . A better underst and ing of EPO regulation , namely oxygen-dependent hydroxylation of the hypoxia-inducible transcription factor ( HIF ) , may enable targeted pharmacological intervention . Here , we tested the ability of fibrotic kidneys and extrarenal tissues to produce EPO . In this phase 1 study , we used an orally active prolyl-hydroxylase inhibitor , FG-2216 , to stabilize HIF independent of oxygen availability in 12 hemodialysis ( HD ) patients , six of whom were anephric , and in six healthy volunteers . FG-2216 increased plasma EPO levels 30.8-fold in HD patients with kidneys , 14.5-fold in anephric HD patients , and 12.7-fold in healthy volunteers . These data demonstrate that pharmacologic manipulation of the HIF system can stimulate endogenous EPO production . Furthermore , the data indicate that deranged oxygen sensing -- not a loss of EPO production capacity -- causes renal anemia OBJECTIVES To examine whether anemia is associated with a higher incidence of recurrent falls . DESIGN Prospect i ve cohort study . SETTING Community-dwelling sample in The Netherl and s. PARTICIPANTS Three hundred ninety-four participants aged 65 to 88 from the Longitudinal Aging Study Amsterdam . MEASUREMENTS Anemia was defined according to World Health Organization criteria as a hemoglobin concentration less than 12 g/dL in women and less than 13 g/dL in men . Falls were prospect ively determined using fall calendars that participants filled out weekly for 3 years . Recurrent fallers were identified as those who fell at least two times within 6 months during the 3-year follow-up . RESULTS Of the 394 persons , 11.9 % ( 18 women and 29 men ) had anemia . The incidence of recurrent falls was 38.3 % of anemic persons versus 19.6 % of nonanemic persons ( P=.004 ) . After adjustment for sex , age , body mass index , and diseases , anemia was significantly associated with a 1.91 times greater risk for recurrent falls ( 95 % confidence interval=1.09 - 3.36 ) . Poor physical function ( indicated by muscle strength , physical performance , and limitations ) partly mediated the association between anemia and incidence of recurrent falls . CONCLUSION Late-life anemia is common and associated with twice the risk of recurrent falls . Muscle weakness and poor physical performance appear to partly mediate this association PURPOSE Anemia is prevalent in old age and is potentially modifiable , but its effects on physical function have not been determined . We examined whether anemia in older persons increases the risk of subsequent decline in physical function , as measured by objective performance-based tests . METHODS Participants in this 4-year prospect i ve cohort study included 1146 participants , aged 71 years or older , living in Iowa and Washington counties , Iowa . Anemia was defined according to World Health Organization ( WHO ) criteria as a hemoglobin concentration below 12 g/dL in women and below 13 g/dL in men . An assessment of st and ing balance , a timed 2.4-m walk , and a timed test of five chair rises were used to assess physical performance ; these were combined into a 0 ( poor ) to 12 ( excellent ) summary scale . RESULTS After adjustment for baseline performance score , health status , and demographic characteristics , anemia was associated with greater mean decline in physical performance over 4 years ; the adjusted mean decline was 2.3 ( 95 % confidence interval [ CI ] : 1.7 to 2.8 ) in subjects with anemia and 1.4 ( 95 % CI : 1.2 to 1.5 ) in those without anemia ( P = 0.003 ) . The association between anemia and greater physical decline was also present in participants who were free of diseases associated with anemia ( cancer , infectious disease , and renal failure ) , and after adjustment for serum cholesterol , iron , and albumin levels . Persons with borderline anemia , a hemoglobin concentration within 1 g/dL above the WHO criteria , also showed greater mean physical decline ( 1.8 ; 95 % CI : 1.5 to 2.2 ) than did those with higher hemoglobin concentrations ( P = 0.02 ) . CONCLUSION This study suggests that anemia in old age is an independent risk factor for decline in physical performance The aim of this study was to prospect ively determine the etiology of anemia in a cohort of community-dwelling older out patients with a comprehensive hematologic evaluation . Participants were men and women age 65 and older with anemia as defined by World Health Organization criteria recruited from outpatient hematology clinics at Stanford Hospital and Clinics ( SHC ) and Veterans Affairs Palo Alto Health Care System ( VAPAHCS ) . Each participant underwent a history and physical examination , followed by a comprehensive hematologic evaluation , which in all participants included complete blood count , red cell indices , review of the blood smear , and assessment of vitamin B12 , folate , iron status and renal function . Additional evaluation was obtained by clinical providers as per their discretion . 190 participants enrolled and completed the evaluation . Twelve percent of participants had iron deficiency anemia . Of those with iron deficiency in whom there was follow-up information , half normalized their hemoglobin in response to iron repletion , and half did not . Thirty-five percent of participants had unexplained anemia . Those with unexplained anemia had mildly increased inflammatory markers compared to non-anemic controls , and , at the lower hemoglobin ranges had relatively low erythropoietin levels . Sixteen percent of participants were categorized as being " suspicious for myelodysplastic syndrome . " Thus , even with comprehensive hematologic evaluation , unexplained anemia is common in older anemic out patients . Iron deficiency anemia is also common and can be difficult to diagnose , and frequently the anemia is not fully corrected with iron repletion PURPOSE To explore the impact of varying hemoglobin levels on mortality , function , and cognition in a representative population of older persons . METHODS Participants in this prospect i ve cohort study included 1 744 men and women , aged 71 years or older , from a r and om household sample living in Durham and surrounding counties in North Carolina . Hemoglobin levels were obtained from participants at baseline in 1992 . Functional status was measured at the 4-year follow-up interview using Katz and instrumental activities of daily living . Cognition was measured using the Short Portable Mental Status Question naire ( SPMSQ ) . Death was determined by search of the National Death Index , and all deaths through 2000 are included . RESULTS Using World Health Organization ( WHO ) criteria , the prevalence of anemia was 24 % . There was a strong racial difference with an odds ratio , adjusted for age , education , estimated glomerular filtration rate and comorbidity of 3.0 ( 95 % CI , 2.3 - 3.9 ) in African Americans compared with Caucasians . The risk ratio for 8-year mortality was 1.7 ( 95 % CI , 1.5 - 2.0 ) for anemic subjects ( P = .0001 ) and did not differ by sex or race . Anemia was strongly associated with poorer physical function ( P = .0001 ) and cognitive function ( P = .0001 ) , and predicted decreases in both over a 4-year period . CONCLUSIONS In an elderly community-based population , anemia is more prevalent in African Americans and is independently associated with increased mortality over 8 years for both races and sexes . Anemia also is a risk factor for functional and cognitive decrease |
711 | 30,699,470 | General health checks are unlikely to be beneficial | BACKGROUND General health checks are common elements of health care in some countries .
They aim to detect disease and risk factors for disease with the purpose of reducing morbidity and mortality .
Most of the commonly used individual screening tests offered in general health checks have been incompletely studied .
Also , screening leads to increased use of diagnostic and therapeutic interventions , which can be harmful as well as beneficial .
It is therefore important to assess whether general health checks do more good than harm .
This is the first up date of the review published in 2012 .
OBJECTIVES To quantify the benefits and harms of general health checks . | Background The benefit of regular multidimensional assessment of older people remains controversial . The majority of trials have been too small to produce adequate evidence to inform policy . Despite the lack of a firm evidence base , UK primary care practitioners ( general practitioners ) are required to offer an annual health check to patients aged 75 years and over . Design Cluster-r and omised factorial trial in primary care comparing a package of assessment s ( i ) universal versus targeted assessment and ( ii ) management by the primary care team ( PC ) or a multidisciplinary geriatric assessment team ( GM ) . The unit of r and omization is the general practice . Methods Older people aged 75 and over eligible for the over 75s health check and excluding those in nursing homes or terminally ill were invited to participate . All participants receive a brief assessment covering all areas of the over 75s check . In the universal arm all participants also receive a detailed health and social assessment by a study nurse while in the targeted arm only participants with a pre-determined number and range of problems at the brief assessment go on to have the detailed assessment . The study nurse follows a st and ard protocol based on results and responses in the detailed assessment to make referrals to ( i ) the r and omised management team ( PC or GM ) ( ii ) other medical services , health care workers or agencies ( iii ) emergency referrals to the GP . The main outcomes are mortality , hospital and institutional admissions and quality of life . 106 practice s and 33,000 older people have been recruited to the trial Aims : There is ongoing debate over the effectiveness of preventive home visits ( PHVs ) for the elderly . A municipality in the north of Sweden carried out a controlled trial of such visits . Healthy seniors aged 75 years and over received two PHVs per year over 2 years . The aim of this study was to do a cost utility analysis of the intervention . Methods : The intervention group ( n=196 ) was compared with a control group ( n=346 ) , and a cost utility analysis was performed . The analysis was carried out with three different time perspectives . Data were source d from official documents and medical and social records . Results : From a societal perspective , using a time period of 4 years , the analysis of PHVs to healthy seniors showed net savings . When including estimated future costs for health and elderly care during gained life years , the result changed from a net saving to a cost of Euro 200,000 . A lifetime perspective also result ed in net savings if the costs of future health and elderly care were not included in the analysis . In this case , the total costs rose to approximately Euro 900,000 . The cost could also be expressed as Euro 14,200 per quality -adjusted life year gained if future costs for elderly care and healthcare were included . Conclusions : PHVs represent a cost-effective intervention in this setting . The costs are justified by the outcomes Objective To quantify the psychological impact of primary care based stepwise screening for type 2 diabetes . Design Controlled trial and comparative study embedded in a r and omised controlled trial . Setting 15 practice s ( 10 screening , five control ) in the ADDITION ( Cambridge ) trial in the east of Engl and . Participants 7380 adults ( aged 40 - 69 ) in the top fourth for risk of having undiagnosed type 2 diabetes ( 6416 invited for screening , 964 controls ) . Interventions Invited for screening for type 2 diabetes or not invited ( controls ) , incorporating a comparative study of subgroups of screening attenders . Attenders completed question naires after a r and om blood glucose test and at 3 - 6 months and 12 - 15 months later . Controls were sent question naires at corresponding time points . Non-attenders were sent question naires at 3 - 6 months and 12 - 15 months . Main outcome measures State anxiety ( Spielberger state anxiety inventory ) , anxiety and depression ( hospital anxiety and depression scale ) , worry about diabetes , and self rated health . Results No significant differences were found between the screening and control participants at any time — for example , difference in means ( 95 % confidence intervals ) for state anxiety after the initial blood glucose test was −0.53 , −2.60 to 1.54 , at 3 - 6 months was 1.51 ( −0.17 to 3.20 ) , and at 12 - 15 months was 0.57 , −1.11 to 2.24 . After the initial test , compared with participants who screened negative , those who screened positive reported significantly poorer general health ( difference in means −0.19 , −0.25 to −0.13 ) , higher state anxiety ( 0.93 , −0.02 to 1.88 ) , higher depression ( 0.32 , 0.08 to 0.56 ) , and higher worry about diabetes ( 0.25 , 0.09 to 0.41 ) , although effect sizes were small . Small but significant trends were found for self rated health across the screening subgroups at 3 - 6 months ( P=0.047 ) and for worry about diabetes across the screen negative groups at 3 - 6 months and 12 - 15 months ( P=0.001 ) . Conclusions Screening for type 2 diabetes has limited psychological impact on patients . Implementing a national screening programme based on the stepwise screening procedure used in the ADDITION ( Cambridge ) trial is unlikely to have significant consequences for patients ' psychological health . Trial registration Current Controlled Trials IS RCT N99175498 Cluster r and omization trials are increasingly being used in primary care research . The main feature of these trials is that patients are nested within large clusters such as physician practice s or communities and the intervention is applied to the cluster . This study design necessitates calculation of intraclass correlation coefficients in order to determine the required sample size . The purpose of this study is to determine intraclass correlation coefficients for a number of outcome measures at the primary care practice level . The CEART study is a r and omized trial testing the effectiveness of translating ATP III guidelines into clinical practice , with primary care physician practice s as the unit of r and omization and patients as the unit of data collection . The intraclass correlation coefficient ( ICC ) was<0.02 and the design effect ranged from 1.0 to 2.3 , respectively , for weight , total cholesterol , LDL , non-HDL , glucose , creatinine , and % at non-HDL goal . For smoking status , body mass index , systolic blood pressure , HDL cholesterol triglycerides , total cholesterol/HDL ratio and % at LDL goal , the ICC was 0.02 - 0.047 and the design effect was 2.6 - 4.1 . The largest ICCs ( 0.05 - 0.12 ) and design effects ( 4.4 - 9.4 ) were found for height and diastolic blood pressure . These findings suggest that cluster r and omization may substantially increase the sample size necessary to maintain adequate statistical power for selected outcomes such as diastolic blood pressure studies compared with simple r and omization for most outcomes evaluated in this study where the design effect is small to moderate . Overall , the ICCs presented will be useful in calculating sample sizes at the primary care level Aim : The aim of this article is to describe the program and study design of our preventive home visit model that targets the specific care needs of Japanese ambulatory frail elders living at home . Methods : The program focused on ambulatory frail elders who were certified as being in the two lowest levels of care need in the Long-Term Care Insurance system and eligible for care , but who were currently not using long-term care services . To provide efficient community-based preventive care , we developed a program model composed of structured assessment s and individualized care recommendations conducted by community care nurses or workers . The assessment protocol focused on locomotion , activities of daily living , social activities , health status , and possibility of abuse . Care needs were clarified every six months over two years . The effectiveness of the program is being assessed in a r and omized controlled trial . Results : A total of 243 elders were assigned r and omly to the preventive home-visit intervention ( n=122 ) or control group ( n=121 ) . Their mean age was 80 years , 76 % were women , and 25 % lived alone . Outcomes including ADLs , IADLs , depression , and social support were measured by postal question naire at baseline , and at 12- and 24-month follow-ups . Utilization of public health or long-term care insurance and service uses over the period is also being documented . Conclusions : The design ’s unique elements of regular evaluation of healthcare needs for targeted individuals within the long-term care insurance context will allow new underst and ing of the role and effectiveness of preventive home visits Objectives To assess whether screening improves the detection of atrial fibrillation ( cluster r and omisation ) and to compare systematic and opportunistic screening . Design Multicentred cluster r and omised controlled trial , with subsidiary trial embedded within the intervention arm . Setting 50 primary care centres in Engl and , with further individual r and omisation of patients in the intervention practice s. Participants 14 802 patients aged 65 or over in 25 intervention and 25 control practice s. Interventions Patients in intervention practice s were r and omly allocated to systematic screening ( invitation for electrocardiography ) or opportunistic screening ( pulse taking and invitation for electrocardiography if the pulse was irregular ) . Screening took place over 12 months in each practice from October 2001 to February 2003 . No active screening took place in control practice s. Main outcome measure Newly identified atrial fibrillation . Results The detection rate of new cases of atrial fibrillation was 1.63 % a year in the intervention practice s and 1.04 % in control practice s ( difference 0.59 % , 95 % confidence interval 0.20 % to 0.98 % ) . Systematic and opportunistic screening detected similar numbers of new cases ( 1.62 % v 1.64 % , difference 0.02 % , −0.5 % to 0.5 % ) . Conclusion Active screening for atrial fibrillation detects additional cases over current practice . The preferred method of screening in patients aged 65 or over in primary care is opportunistic pulse taking with follow-up electrocardiography . Trial registration Current Controlled Trials IS RCT N19633732 OBJECTIVES To apply and evaluate the effects of a program for computer generated physician reminders , integrated with an electronic patient record ( EPR ) system , for opportunistic health screening in elderly patients . DESIGN A pilot study design ed as a 20-month clinical trial with a control group and a 20-month non-intervention follow-up using a computer reminder program that selects patients for screening in five intervention areas ( diabetes , hypertension , cobalamin deficiency , hypothyroidism and anaemia ) . SETTING Four primary health care ( PHC ) centres in suburban Stockholm . SUBJECTS The intervention was design ed for patients 70 years or older from one health care centre who visited a general practitioner ( GP ) during the first 20-month period . Patients from the three remaining centres served as controls . MAIN OUTCOME MEASURES The number of patients who underwent the tests , who had pathological test results , new diagnoses and new pharmacological treatments in both patient groups . RESULTS In total , 602 patients underwent screening and 1989 were controls . There was a statistically significant , moderate or marked increase ( 13 - 75 % ) in the number of patients who were tested in all five intervention areas . An increase in pathological test results ( 1 - 8 % ) was found in two areas : hypertension and cobalamin deficiency . There was an increase in the number of patients with the diagnosis of cobalamin deficiency during the study . At follow-up a decrease in new diagnoses for anaemia was found . CONCLUSION The system seems to be associated with a moderate to large increase in laboratory and manual screening tests for both established and new screening areas . The effect on clinical outcomes was found mainly in a not-yet-established screening area ( cobalamin deficiency ) , indicating that the system may be clinical ly useful when introducing new screening services Multiphasic screening as a case-finding tool was evaluated in a r and omized , controlled study . For each of 112 physicians , a patient was assigned to one of three groups : multiphasic screening group ( SG ) , chart abstract group ( AG ) , or chart review group ( RG ) . Medical problem lists constructed before and after receiving additional information were compared . Physicians for 36 SG patients identified considerably more new medical problems , both total ( 77 ) and ones they considered important ( 25 ) , than 40 AG physicians ( 14 and 8) and 36 RG physicians ( 4 and 0 ) . One year later , 38 of the 95 newly identified problems had been acted on , 31 in the SG . Medical care was affected in nine patients : six in SG , two in AG , and one in RG . Multiphasic screening may help physicians identify new medical problems in clinic patients Background The global burden of the major vascular diseases is projected to rise and to remain the dominant non-communicable disease cluster well into the twenty first century . The Department of Health in Engl and has developed the NHS Health Check service as a policy initiative to reduce population vascular disease risk . The aims of this study were to monitor population changes in cardiovascular disease ( CVD ) risk factors over the first year of the new service and to assess the value of tailored lifestyle support , including motivational interview with ongoing support and referral to other services . Methods R and omised trial comparing NHS Health Check service only with NHS Health Check service plus additional lifestyle support in Stoke on Trent , Engl and . Thirty eight general practice s and 601 ( 365 usual care , 236 additional lifestyle support ) patients were recruited and r and omised independently between September 2009 and February 2010 . Changes in population CVD risk between baseline and one year follow-up were compared , using intention-to-treat analysis . The primary outcome was the Framingham 10 year CVD risk score . Secondary outcomes included individual modifiable risk measures and prevalence of individual risk categories . Additional lifestyle support included referral to a lifestyle coach and free sessions as needed for : weight management , physical activity , cook and eat and positive thinking . Results Average population CVD risk decreased from 32.9 % to 29.4 % ( p < 0.001 ) in the NHS Health Check only group and from 31.9 % to 29.2 % ( p < 0.001 ) in the NHS Health Check plus additional lifestyle support group . There was no significant difference between the two groups at either measurement point . Prevalence of high blood pressure , high cholesterol and smoking were reduced significantly ( p < 0.01 ) in both groups . Prevalence of central obesity was reduced significantly ( p < 0.01 ) in the group receiving additional lifestyle support but not in the NHS Health Check only group . Conclusions The NHS Health Check service in Stoke on Trent result ed in significant reduction in estimated population CVD risk . There was no evidence of further benefit of the additional lifestyle support services in terms of absolute CVD risk reduction Abstract The drop-out problem was studied in a r and omly selected population sample of men invited to a primary preventive trial against coronary heart disease among middle-aged men . Participants and non- participants in the intervention group were compared with regard to mortality , causes of death , autopsy findings , morbidity and sobriety . The non-participation group was characterized by a somewhat higher prevalence of chronic diseases and alcoholic problems . These features were more pronounced in subjects who died during the follow-up compared to still living subjects . Mortality , total as well as cause-specific , was considerably higher among non- participants . The death rate was higher in the non-participation group irrespective of duration of sick leave . The amount of coronary atherosclerosis , evaluated post-mortem , was essentially the same in those who died in the participation and non-participation groups . The difference in characteristics between participants and non- participants affects the possibilities of generalization to the total population under study . Similar differences between participants and non- participants are certainly present in other studies too Background Regarding demographic changes in Germany it can be assumed that the number of elderly and the result ing need for long term care is increasing in the near future . It is not only an individual 's interest but also of public concern to avoid a nursing home admission . Current evidence indicates that preventive home visits can be an effective way to reduce the admission rate in this way making it possible for elderly people to stay longer at home than without home visits . As the effectiveness and cost-effectiveness of preventive home visits strongly depends on existing services in the social and health system existing international results can not be merely transferred to Germany . Therefore it is necessary to investigate the effectiveness and cost-effectiveness of such an intervention in Germany by a r and omized controlled trial . Methods The trial is design ed as a prospect i ve multi-center r and omized controlled trial in the cities of Halle and Leipzig . The trial includes an intervention and a control group . The control group receives usual care . The intervention group receives three additional home visits by non-physician health professionals ( 1 ) geriatric assessment , ( 2 ) consultation , ( 3 ) booster session . The nursing home admission rate after 18 months will be defined as the primary outcome . An absolute risk reduction from a 20 % in the control-group to a 7 % admission rate in the intervention group including an assumed drop out rate of 30 % result ed in a required sample size of N = 320 ( n = 160 vs. n = 160).Parallel to the clinical outcome measurement the intervention will be evaluated economically . The economic evaluation will be performed from a society perspective . Discussion To the authors ' knowledge for the first time a trial will investigate the effectiveness and cost-effectiveness of preventive home visits for people aged 80 and over in Germany using the design of a r and omized controlled trial . Thus , the trial will contribute to the existing evidence on preventive home visits especially in Germany Background The Health Improvement and Prevention Study ( HIPS ) study aims to evaluate the capacity of general practice to identify patients at high risk for developing vascular disease and to reduce their risk of vascular disease and diabetes through behavioural interventions delivered in general practice and by the local primary care organization . Methods / Design HIPS is a stratified r and omized controlled trial involving 30 general practice s in NSW , Australia . Practice s are r and omly allocated to an ' intervention ' or ' control ' group . General practitioners ( GPs ) and practice nurses ( PNs ) are offered training in lifestyle counselling and motivational interviewing as well as practice visits and patient educational re sources . Patients enrolled in the trial present for a health check in which the GP and PN provide brief lifestyle counselling based on the 5As model ( ask , assess , advise , assist , and arrange ) and refer high risk patients to a diet education and physical activity program . The program consists of two individual visits with a dietician or exercise physiologist and four group sessions , after which patients are followed up by the GP or PN . In each practice 160 eligible patients aged between 40 and 64 years are invited to participate in the study , with the expectation that 40 will be eligible and willing to participate . Evaluation data collection consists of ( 1 ) a practice question naire , ( 2 ) GP and PN question naires to assess preventive care attitudes and practice s , ( 3 ) patient question naire to assess self-reported lifestyle behaviours and readiness to change , ( 4 ) physical assessment including weight , height , body mass index ( BMI ) , waist circumference and blood pressure , ( 5 ) a fasting blood test for glucose and lipids , ( 6 ) a clinical record audit , and ( 7 ) qualitative data collection . All measures are collected at baseline and 12 months except the patient question naire which is also collected at 6 months . Study outcomes before and after the intervention is compared between intervention and control groups after adjusting for baseline differences and clustering at the level of the practice . Discussion This study will provide evidence of the effectiveness of a primary care intervention to reduce the risk of cardiovascular disease and diabetes in general practice patients . It will inform current policies and programs design ed to prevent these conditions in Australian primary health care . Trial Registration Summary Background The increasing prevalence of type 2 diabetes poses a major public health challenge . Population -based screening and early treatment for type 2 diabetes could reduce this growing burden . However , uncertainty persists around the benefits of screening for type 2 diabetes . We assessed the effect of a population -based stepwise screening programme on mortality . Methods In a pragmatic parallel group , cluster-r and omised trial , 33 general practice s in eastern Engl and were r and omly assigned by the method of minimisation in an unbalanced design to : screening followed by intensive multifactorial treatment for people diagnosed with diabetes ( n=15 ) ; screening plus routine care of diabetes according to national guidelines ( n=13 ) ; and a no-screening control group ( n=5 ) . The study population consisted of 20 184 individuals aged 40–69 years ( mean 58 years ) , at high risk of prevalent undiagnosed diabetes , on the basis of a previously vali date d risk score . In screening practice s , individuals were invited to a stepwise programme including r and om capillary blood glucose and glycated haemoglobin ( HbA1c ) tests , a fasting capillary blood glucose test , and a confirmatory oral glucose tolerance test . The primary outcome was all-cause mortality . All participants were flagged for mortality surveillance by the Engl and and Wales Office of National Statistics . Analysis was by intention-to-screen and compared all-cause mortality rates between screening and control groups . This study is registered , number IS RCT N86769081 . Findings Of 16 047 high-risk individuals in screening practice s , 15 089 ( 94 % ) were invited for screening during 2001–06 , 11 737 ( 73 % ) attended , and 466 ( 3 % ) were diagnosed with diabetes . 4137 control individuals were followed up . During 184 057 person-years of follow up ( median duration 9·6 years [ IQR 8·9–9·9 ] ) , there were 1532 deaths in the screening practice s and 377 in control practice s ( mortality hazard ratio [ HR ] 1·06 , 95 % CI 0·90–1·25 ) . We noted no significant reduction in cardiovascular ( HR 1·02 , 95 % CI 0·75–1·38 ) , cancer ( 1·08 , 0·90–1·30 ) , or diabetes-related mortality ( 1·26 , 0·75–2·10 ) associated with invitation to screening . Interpretation In this large UK sample , screening for type 2 diabetes in patients at increased risk was not associated with a reduction in all-cause , cardiovascular , or diabetes-related mortality within 10 years . The benefits of screening might be smaller than expected and restricted to individuals with detectable disease . Funding Wellcome Trust ; UK Medical Research Council ; National Health Service research and development support ; UK National Institute for Health Research ; University of Aarhus , Denmark ; Bio-Rad Purpose . To evaluate the efficacy of computerized health risk appraisal ( HRA ) when it is incorporated into a periodic health examination at the worksite . Design . A r and omized , controlled trial comparing change in health behaviors for a 6-month follow-up period was conducted . Setting . A large financial services firm in New York City . Subjects . A total of 161 employees who volunteered for a worksite periodic health examination . Intervention . All employees received a physician-based history and physical examination , including laboratory tests , and were counseled on the basis of the results . Half the employees were r and omly assigned , to receive an HRA report , with counseling from the 1984 version of the Centers for Disease Control HRA , whereas the other half completed the HRA question naire but received no HRA report or counseling . Measures . Blood pressure , cholesterol , and weight were measured by project staff physical activity and seatbelt use were measured by self-report , and change in computerized appraised age was calculated by the HRA program . Results . Evaluation of the 90 participants who returned for follow-up revealed a statistically significant improvement in computerized appraised age and physical activity in those who had received the HRA report and counseling compared with those who had not ( p < .05 ) , and also showed trends toward greater improvement in blood pressure , weight , and seatbelt use . Conclusions . Results provide support for the efficacy of HRA when incorporated into a periodic health examination at the worksite Background There is a wealth of evidence regarding the detrimental impact of excessive alcohol consumption . In older population s excessive alcohol consumption is associated with increased risk of coronary heart disease , hypertension , stroke and a range of cancers . Alcohol consumption is also associated with an increased risk of falls , early onset of dementia and other cognitive deficits . Physiological changes that occur as part of the ageing process mean that older people experience alcohol related problems at lower consumption levels . There is a strong evidence base for the effectiveness of brief psychosocial interventions in reducing alcohol consumption in population s identified opportunistically in primary care setting s. Stepped care interventions involve the delivery of more intensive interventions only to those in the population who fail to respond to less intensive interventions and provide a potentially re source efficient means of meeting the needs of this population . Methods / design The study design is a pragmatic prospect i ve multi-centre two arm r and omised controlled trial . The primary hypothesis is that stepped care interventions for older hazardous alcohol users reduce alcohol consumption compared with a minimal intervention at 12 months post r and omisation . Potential participants are identified using the AUDIT question naire . Eligible and consenting participants are r and omised with equal probability to either a minimal intervention or a three step treatment approach . The step treatment approach incorporates as step 1 behavioural change counselling , step 2 three sessions of motivational enhancement therapy and step 3 referral to specialist services . The primary outcome is measured using average st and ard drinks per day and secondary outcome measures include the Drinking Problems Index , health related quality of life and health utility . The study incorporates a comprehensive economic analysis to assess the relative cost-effectiveness of the interventions . Discussion The paper presents a protocol for the first pragmatic r and omised controlled trial evaluating the effectiveness and cost-effectiveness of stepped care interventions for older hazardous alcohol users in primary care . Trial registration IS RCT Background Primary care provides most of the evidence -based chronic disease prevention and screening services offered by the healthcare system . However , there remains a gap between recommended preventive services and actual practice . This trial ( the BETTER Trial ) aim ed to improve preventive care of heart disease , diabetes , colorectal , breast and cervical cancers , and relevant lifestyle factors through a practice facilitation intervention set in primary care . Methods Pragmatic two-way factorial cluster RCT with Primary Care Physicians ’ practice s as the unit of allocation and individual patients as the unit of analysis . The setting was urban Primary Care Team practice s in two Canadian provinces . Eight Primary Care Team practice s were r and omly assigned to receive the practice -level intervention or wait-list control ; 4 physicians in each team ( 32 physicians ) were r and omly assigned to receive the patient-level intervention or wait-list control . Patients r and omly selected from physicians ’ rosters were stratified into two groups : 1 ) general and 2 ) moderate mental illness . The interventions involved a multifaceted , evidence -based , tailored practice -level intervention with a Practice Facilitator , and a patient-level intervention involving a one-hour visit with a Prevention Practitioner where patients received a tailored ‘ prevention prescription ’ . The primary outcome was a composite Summary Quality Index of 28 evidence -based chronic disease prevention and screening actions with pre-defined targets , expressed as the ratio of eligible actions at baseline that were met at follow-up . A cost-effectiveness analysis was conducted . Results 789 of 1,260 ( 63 % ) eligible patients participated . On average , patients were eligible for 8.96 ( SD 3.2 ) actions at baseline . In the adjusted analysis , control patients met 23.1 % ( 95 % CI : 19.2 % to 27.1 % ) of target actions , compared to 28.5 % ( 95 % CI : 20.9 % to 36.0 % ) receiving the practice -level intervention , 55.6 % ( 95 % CI : 49.0 % to 62.1 % ) receiving the patient-level intervention , and 58.9 % ( 95 % CI : 54.7 % to 63.1 % ) receiving both practice - and patient-level interventions ( patient-level intervention versus control , P < 0.001 ) . The benefit of the patient-level intervention was seen in both strata . The extra cost of the intervention was $ 26.43CAN ( 95 % CI : $ 16 to $ 44 ) per additional action met . Conclusions A Prevention Practitioner can improve the implementation of clinical ly important prevention and screening for chronic diseases in a cost-effective manner Background Because of their complex clinical presentations and needs frail elderly people require another approach than people who age without many complications . Several inpatient geriatric health services have proven effectiveness in frail persons . However , the wish to live independently and policies that promote independent living as an answer to population aging call for community intervention models for frail elderly people . Maybe models such as preventive home visits , comprehensive geriatric assessment , and intermediate care qualify , but their efficacy is controversial , especially in frail elderly persons living in the community . With the Dutch EASYcare Study Geriatric Intervention Programme ( DGIP ) we developed a model to study effectiveness of problem based community intervention models in frail elderly people . Methods / Design DGIP is a community intervention model for frail elderly persons where the GP refers elderly patients with a problem in cognition , mood , behaviour , mobility , and nutrition . A geriatric specialist nurse applies a guideline -based intervention with a limited number of follow up visits . The intervention starts with the application of the EASYcare instrument for geriatric screening . The EASYcare instrument assesses ( instrumental ) activities of daily life , cognition , mood , and includes a goal setting item . During the intervention the nurse regularly consults the referring GP and a geriatrician . Effects on functional performance ( Groningen Activity Restriction Scale ) , health related quality of life ( MOS-20 ) , and carer burden ( Zarit Burden Interview ) are studied in an observer blinded r and omised controlled trial . 151 participants were r and omised over two treatment arms – DGIP and regular care – using pseudo cluster r and omisation . We are currently performing the follow up visits . These visits are planned three and six months after inclusion . Process measures and cost measures will be recorded . Intention to treat analyses will focus on post intervention differences between treatment groups . Discussion The design of a trial evaluating the effects of a community intervention model for frail elderly people was presented . The problem-based participant selection procedure satisfied ; few patients that the GP referred did not meet our eligibility criteria . The use of st and ard terminology makes detailed insight into the contents of our intervention possible using terminology others can underst and well Background Screening for vascular disease , risk assessment and management are encouraged in general practice however there is limited evidence about the emotional impact on patients . The Health Improvement and Prevention Study evaluated the impact of a general practice -based vascular risk factor intervention on behavioural and physiological risk factors in 30 Australian practice s. The primary aim of this analysis is to investigate the psychological impact of participating in the intervention arm of the trial . The secondary aim is to identify the mediating effects of changes in behavioural risk factors or BMI . Methods This study is an analysis of a secondary outcome from a cluster r and omized controlled trial . Patients , aged 40–65 years , were r and omly selected from practice records . Those with pre-existing cardiovascular disease were excluded . Socio-demographic details , behavioural risk factors and psychological distress were measured at baseline and 12 months . The Kessler Psychological Distress Score ( K10 ) was the outcome measure for multi-level , multivariable analysis and a product-of-coefficient test to assess the mediating effects of behaviour change . Results Baseline data were available 384 participants in the intervention group and 315 in the control group . Twelve month data were available for 355 in the intervention group and 300 in the control group . The K10 score of patients in the intervention group ( 14.78 , SD 5.74 ) was lower at 12 months compared to the control group ( 15.97 , SD 6.30 ) . K10 at 12 months was significantly associated with the score at baseline and being unable to work but not with age , gender , change in behavioural risk factors or change in BMI . Conclusions The reduction of K10 in the intervention group demonstrates that a general practice based intervention to identify and manage vascular risk factors did not adversely impact on the psychological distress of the participants . The impact of the intervention on distress was not mediated by a change in the behavioural risk factors or BMI , suggesting that there must be other mediators that might explain the positive impact of the intervention on emotional wellbeing . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12607000423415 OBJECTIVES To investigate the impact of general health screenings and discussion s with general practitioners on the cardiovascular risk profile of a r and om population of patients . STUDY DESIGN A population -based , r and omized , controlled , 5-year follow-up trial conducted in a primary care setting . POPULATION The study group consisted of 2000 patients , r and omly selected middle-aged men and women aged 30 to 50 years from family practice s in the district of Ebeltoft , Denmark . Of these patients , 1507 ( 75.4 % ) agreed to participate . Patients were r and omized into ( 1 ) a control group who did not receive health screenings , ( 2 ) an intervention group that received 2 health screenings , ( 3 ) an intervention group that received both the 2 screenings and a 45-minute follow-up consultation annually with their general practitioner . OUTCOMES MEASURED Cardiovascular risk score ( CRS ) , body mass index ( BMI ) , blood pressure , serum cholesterol , carbon monoxide in expiratory air , and tobacco use . RESULTS After 5 years , the CRS , BMI , and serum cholesterol levels were lower in the intervention groups compared with the control group . The improved outcome was greater in the baseline risk groups . The number of patients with elevated CRS in the intervention groups was approximately half the number of patients with elevated CRS in the control group . The difference was not a result of medication use . There was no difference between the group that received consultations after the screenings and the group that had health screenings alone . CONCLUSIONS Health screenings reduced the CRS in the intervention groups . After 5 years of follow-up , the number of persons at elevated cardiovascular risk was about half that expected , based on the prevalence/proportion in a population not receiving the health checks ( the control group ) . The impact of intervention was higher among at-risk individuals . Consultations about health did not appear to improve the cardiovascular profile of the study population Incidence and mortality results are presented from an international controlled trial of multifactorial prevention of coronary heart disease , involving r and omization of 66 factories ( 49 781 men ) in U.K. , Belgium , Italy and Pol and ( Cracow ) . Results for Pol and ( Warsaw ) are not yet complete . Net average reductions in risk factors ( all subjects ) were 1.2 % for plasma cholesterol , 8.9 % for daily cigarettes , 0.4 % for weight , 2.0 % for systolic blood pressure , and 11.1 % for a combined risk estimate . Greater reductions occurred in high-risk subjects ( 19.4 % for the combined estimate ) . The net overall reduction in CHD rates was 7.4 % ( 95 % confidence interval -29 to + 15 % ) for deaths ( 722 cases ) , and 3.9 % ( 95 % confidence interval -10 to + 2 % ) for fatal CHD + non-fatal myocardial infa rct ion ( 1502 cases ) . Among men aged 40 - 49 the reduction for this end-point was 15 % ; at ages 50 - 59 there was a small net increase . All-causes deaths after an early adverse trend showed 2.7 % reduction overall . There were large differences between centres , ranging from a 5 % net increase in CHD for U.K. to a decrease of 24 % in Belgium . In Belgium the decrease both in CHD and in all deaths was significant at the 5 % level . The effect on CHD in the different centres correlated broadly with their changes in risk factors . It is concluded that reduction in major coronary risk factors in industrial population s is possible , but it depends on adequate re sources ; the results support the hypotheses that CHD risk in middle-aged men is reversible and that community intervention can be beneficial OBJECTIVE To analyze mental distress in relation to participation in lifestyle intervention . METHODS In 2000 - 2001 a total of 1948 consecutive participants , living in the suburbs of Copenhagen , were asked to complete a short version of SCL-90-R ( anxiety , depression , and somatization ) before screening , immediately after screening , and one and 10 months after screening . The screening classified participants into high or low risk individuals . High risk individuals received personal lifestyle counselling and were r and omized to either group-based counselling ( A ) or referred care ( B ) . Multilevel regression models taking into account repeated measurements and missing data at follow-up were performed . RESULTS Before screening , high risk individuals had higher scores on anxiety , depression , and somatization than low risk individuals . All categories of participants decreased in scores after screening . The scores increased after 1 month , but were still significantly lower than before screening . After 10 months , low risk individuals and high risk individuals in group A still had significantly lower scores ( except for depression ) compared with pre-screening levels , whereas high risk individuals in group B reached the pre-screening level ( except for anxiety ) . CONCLUSION Screening for risk of cardiovascular disease followed by health counselling does not give rise to mental distress , but has a temporary beneficial effect Background Preventive home visits to elderly people by public health nurses aim to maintain or improve the functional status of elderly and reduce the use of institutional care services . A number of trials that investigated the effects of home visits show positive results , but others do not . The outcomes can depend on differences in characteristics of the intervention programme , but also on the selection of the target population . A risk group approach seems promising , but further evidence is needed . We decided to carry out a study to investigate the effects in a population of elderly with ( perceived ) poor health rather than the general population . Also , we test whether nurses who are qualified at a lower professional level ( home nurses instead of public health nurses ) are able to obtain convincing effects . The results of this study will contribute to the discussion on effective public health strategies for the aged . Methods / design The study is carried out as a parallel group r and omised trial . To screen eligible participants , we sent a postal question naire to 4901 elderly people ( 70–84 years ) living at home in a town in the south of the Netherl and s. After applying inclusion criteria ( e.g. , self-reported poor health status ) and exclusion criteria ( e.g. , those who already receive home nursing care ) , we selected 330 participants . They entered the r and omisation procedure ; 160 were allocated to the intervention group and 170 to the control group . The intervention consists of ( at least ) 8 systematic home visits over an 18 months period . Experienced home nurses from the local home care organisation carry out the visits . The control group receives usual care . Effects on health status are measured by means of postal question naires after 12 months , 18 months ( the end of the intervention period ) and after 24 months ( the end of 6-months follow-up ) , and face-to-face interviews after 18 months . Data on mortality and service use are continuously registered during 24 months . A cost-benefit analysis is included . The design and setting of the study , the selection of eligible participants and the study interventions are described in this article . Other included items are : the primary and secondary outcome measures , the statistical analysis and the economic evaluation Abstract Background The objective of this article is to describe the design of an evaluation of the cost-effectiveness of systematic home visits by nurses to frail elderly primary care patients . Pilot objectives were : 1 . To determine the feasibility of postal multidimensional frailty screening instruments ; 2 . to identify the need for home visits to elderly . Methods Main study : The main study concerns a r and omized controlled in primary care practice s ( PCP ) with 18 months follow-up and blinded PCPs . Frail persons aged 75 years or older and living at home but neither terminally ill nor demented from 33 PCPs were eligible . Trained community nurses ( 1 ) visit patients at home and assess the care needs with the Resident Assessment Instrument-Home Care , a multidimensional computerized geriatric assessment instrument , enabling direct identification of problem areas ; ( 2 ) determine the care priorities together with the patient ; ( 3 ) design and execute interventions according to protocol s ; ( 4 ) and visit patients at least five times during a year in order to execute and monitor the care-plan . Controls receive usual care . Outcome measures are Quality of life , and Quality Adjusted Life Years ; time to nursing home admission ; mortality ; hospital admissions ; health care utilization . Pilot 1 : Three brief postal multidimensional screening measures to identify frail health among elderly persons were tested on percentage complete item response ( selected after a literature search ): 1 ) Vulnerable Elders Screen , 2 ) Strawbridge 's frailty screen , and 3 ) COOP-WONCA charts . Pilot 2 : Three nurses visited elderly frail patients as identified by PCPs in a health center of 5400 patients and used an assessment protocol to identify psychosocial and medical problems . The needs and experiences of all participants were gathered by semi-structured interviews . Discussion The design holds several unique elements such as early identification of frail persons combined with case-management by nurses . From two pilots we learned that of three potential postal frailty measures , the COOP-WONCA charts were completed best by elderly and that preventive home visits by nurses were positively evaluated to have potential for quality of care improvement OBJECTIVES This study was undertaken to determine whether adding a benefit for preventive services to older Medicare beneficiaries would affect utilization and costs under Medicare . METHODS The demonstration used an experimental design , enrolling 4195 older , community-dwelling Medicare recipients . Medicare cl aims data for the 2 years in which the preventive visits occurred were compared for the intervention ( n = 2105 ) and control ( n = 2090 ) groups . Monthly allowable charges for Part A and Part B services and number of hospital discharges and ambulatory visits were compared . RESULTS There were no significant differences in the charges between the groups owing to the intervention , although total charges were somewhat lower for the intervention group even when the cost of the intervention was included . Charges for both groups rose significantly as would be expected for an aging population . A companion paper describes a modest health benefit . CONCLUSIONS There appears to be a modest health benefit with no negative cost impact . This finding gives an early quantitative basis for the discussion of whether to extend Medicare benefits to include a general preventive visit from a primary care clinician OBJECTIVE To illustrate the geographical West-to-East division of coronary heart disease ( CHD ) by comparing a population from Sweden , that represents a Western country to a population from Estonia , that represents an Eastern country . Estonia has an approximately 2 - 4-fold higher CHD prevalence for 55-year-old women and men , respectively , than Sweden . DESIGN R and omized screening of 35- and 55-year-old men and women in Sollentuna county , Sweden and Tartu county , Estonia . Eight hundred subjects , 100 from each cohort , were invited to participate in the study , 272 Swedes and 277 Estonians participated . SETTING Preventive cardiology , administered by a primary health care centre at the Karolinska Hospital , Sweden and a cardiology centre at Tartu University Hospital , Estonia . MAIN OUTCOME MEASURES The CHD risk factors ( smoking , blood pressure , concentrations of lipoproteins , fibrinogen , and glucose ) and certain environmental factors and attitudes related to CHD risk by question naires ( fat-type and alcohol ingestion , self-assessed rating of CHD susceptibility ) . RESULTS Of the 55-year-old men , 57 % smoked in Estonia and 20 % smoked in Sweden . Similar , although less pronounced differences showing higher smoking prevalence , were seen for 35-year-old Estonian men and women , whilst for 55-year-old women , less than 20 % smoked in either country . Estonian 55-year-old women had lower HDL cholesterol and higher LDL cholesterol serum concentrations than Swedish 55-year-old women . Estonians reportedly ate food containing more saturated fats than Swedes , as indicated by the scale-score question naire . Estonians , relative to Swedes , rated their chance of developing CHD higher , and paradoxically , Estonians did to a much lesser degree believe that life style influences the risk of developing CHD . CONCLUSIONS Elevated smoking prevalence is a striking difference between the Estonian and Swedish population s likely to explain the much higher CHD prevalence in Estonian men . The lower HDL cholesterol and higher LDL cholesterol in Estonian 55-year-old women may explain the higher CHD prevalence in Estonian women . Furthermore , the SWESTONIA CHD study ( i.e. comparison between Sweden and Estonia ) shows several environmental differences between the countries population s related to fat content in food , alcohol drinking patterns , and views on CHD risk and the importance of lifestyle intervention , that could contribute to the higher CHD prevalence in Estonia OBJECTIVES To determine whether preventive in-home comprehensive geriatric assessment ( CGA ) prevents functional decline in community-dwelling older persons with different baseline functional status : ( 1 ) without any basic activities of daily living ( BADL ) dependency at baseline ; and ( 2 ) without any instrumental ADL ( IADL ) and basic ADL dependency at baseline . DESIGN Subgroup analyses of a 3-year r and omized controlled trial . SETTING The city of Santa Monica , California . PARTICIPANTS Participants came from the original population ( n = 414 ) of community-living older persons aged 75 years and older who participated in a trial testing the effectiveness of annual preventive in-home CGA . For the first subgroup analysis , we excluded subjects ( n = 27 ) who were dependent in one or more BADL before r and omization ( final sample size , n = 387 ) ; for the second subgroup analysis , we excluded 93 additional subjects who were dependent in one or more IADL before r and omization ( final sample size , n = 294 ) . INTERVENTION Annual preventive in-home CGA , with quarterly home visits by gerontologic nurse practitioners , for 3 years . MEASUREMENTS Functional status data were collected through yearly in-home interviews by independent observers . Subjects were classified as ( 1 ) independent in both BADL and IADL , ( 2 ) dependent in IADL but independent in BADL , or ( 3 ) dependent in both IADL and BADL . RESULTS In both subgroup analyses , there was no difference in survival between intervention and control subjects . In the subgroup with no BADL impairment at baseline , intervention subjects spent significantly fewer days dependent in both BADL and IADL during each year of the study ( 5 days vs 14 days , P = .022 ; 13 vs 33 , P = .016 ; and 19 vs 44 , P = .014 for years 1 , 2 , and 3 , respectively ) and over all 3 years combined ( 36 days vs 92 days , P = .016 ) in bivariate analyses . In multivariate analyses , the intervention reduced time spent in complete ( BADL and IADL ) dependency ( P = .028 ) . In the subgroup of subjects without any IADL or BADL impairment at baseline , no significant differences were apparent in the number of days spent in complete independence and days spent in complete dependency . Intervention group subjects spent more days in partial dependency during Year 1 ( 24 days vs 9 days , P = .021 ) , but the difference was not significant during Year 2 ( 47 vs 29 , P = .088 ) , Year 3 ( 49 vs 41 , P = .370 ) , and over all 3 years combined ( 120 vs 79 , P = .123 ) as well as in multivariate analysis ( P = .062 ) . CONCLUSION These findings support the hypothesis that in-home preventive visits delay the onset of disability in people without initial BADL impairment . Further studies in larger sample s are needed to determine optimal intervention strategies and effectiveness among well functioning older people Aims : In controlled intervention studies , a selective non-response or refusal to participate at baseline may bias measurable effects of the intervention . The aim of this study was to compare mortality and nursing home admission among older persons who accepted ( participants ) and older person who declined ( non- participants ) to join a controlled feasibility trial , and to describe and evaluate defined subgroups of non- participants . Methods : Prospect i ve controlled three-year intervention study ( 1999—2001 ) in 34 Danish municipalities with five-year follow-up . R and omization and intervention ( education of municipality employees ) was done at municipality level . In total 5,788 home-dwelling 75- and 80-year-olds living in these municipalities were invited to participate in the study . Written consent was obtained from 4,060 persons ( participation rate 71 % ) . Results : During five-year follow-up non- participants had a higher mortality rate ( survival analysis risk ratio RR=1.5 , 95 % CI=1.3—1.7 , p<0.0001 ) and a higher rate of nursing home admissions ( RR=1.7 , 95 % CI=1.3— 2.1 , p<0.0001 ) compared with participants . Subgroups of non- participants describing themselves as ` ` too ill ' ' and persons ` ` not reached ' ' had a significantly higher mortality rate and risk of admission to nursing home than participants , whereas the subgroups of non- participants describing themselves as ` ` too healthy ' ' and having ` ` another reason for refusal ' ' did not differ from the participants . There was no difference in mortality rates between non- participants living in intervention municipalities compared with non- participants living in control municipalities . Conclusions : Mortality and nursing home admissions were higher among non- participants . Selection participation bias was of no clinical importance since subgroups of non- participants eligible for the intervention did not differ from the participants Objective : To improve the delivery of preventive care in a medical clinic , a controlled trial was conducted of two interventions that were expected to influence delivery of preventive services differently , depending on level of initiative required of the physician or patient to complete a service . Design : A prospect i ve , controlled trial of five-months ’ duration . Setting : A university hospital-based , general medical clinic . Participants : Thirty-nine junior and senior medical residents who saw patients in stable clinic teams throughout the study .Intervention : A computerized reminder system for physicians and a patient question naire and educational h and out on preventive care . Measurements and main results : Delivery of five of six audited preventive services improved significantly after the interventions were introduced . The computerized reminder alone increased completion rates of services that relied primarily on physician initiative ; the question naire alone increased completion rate of the service that depended more on patient compliance as well as on some physician-dependent services . Both interventions used together were slightly less effective in improving performance of physician-dependent services than the computerized reminder used alone . Conclusions : These interventions can improve the delivery of preventive care but they differ in their impacts on physician and patient behaviors . Overall , the computer reminder was the more effective intervention BACKGROUND Screening tests for sub clinical cardiovascular disease , such as markers of atherosclerosis , are increasingly used in clinical prevention to identify individuals at high cardiovascular risk . Being aware of these test results might also enhance patient motivation to change unhealthy behaviors but the effectiveness of such a screening strategy has been poorly studied . METHODS The CAROtid plaque Screening trial on Smoking cessation ( CAROSS ) is a r and omized controlled trial in 530 regular smokers aged 40 - 70 years to test the hypothesis that carotid plaque screening will influence smokers ' behavior with an increased rate of smoking cessation ( primary outcome ) and an improved control of other cardiovascular risk factors ( secondary outcomes ) after 1-year follow-up . All smokers will receive a brief advice for smoking cessation , and will subsequently be r and omly assigned to either the intervention group ( with plaques screening ) or the control group ( without plaque screening ) . Carotid ultrasound will be conducted with a st and ard protocol . Smokers with at least one carotid plaque will receive pictures of their own plaques with a structured explanation on the general significance of plaques . To ensure equal contact conditions , smokers not undergoing ultrasound and those without plaque will receive a relevant explanation on the risks associated with tobacco smoking . Study outcomes will be compared between smokers r and omized to plaque screening and smokers not su bmi tted to plaque screening . SUMMARY This will be the first trial to assess the impact of carotid plaque screening on 1-year smoking cessation rates and levels of control of other cardiovascular risk factors Background To determine the effectiveness of a single checklist reminder form to improve the delivery of preventive health services at adult health check-ups in a family practice setting . Methods A prospect i ve cluster r and omized controlled trial was conducted at four urban family practice clinics among 38 primary care physicians affiliated with the University of Toronto . Preventive Care Checklist Forms © were created to be used by family physicians at adult health check-ups over a five-month period . The sex-specific forms incorporate evidence -based recommendations on preventive health services and documentation space for routine procedures such as physical examination . The forms were used in two intervention clinics and two control clinics . Rates and relative risks ( RR ) of the performance of 13 preventive health maneuvers at baseline and post-intervention and the percentage of up-to- date preventive health services delivered per patient were compared between the two groups . Results R and omly-selected charts were review ed at baseline ( n = 509 ) and post-intervention ( n = 608 ) . Baseline rates for provision of preventive health services ranged from 3 % ( fecal occult blood testing ) to 93 % ( blood pressure measurement ) , similar to other setting s. The percentage of up-to- date preventive health services delivered per patient at the end of the intervention was 48.9 % in the control group and 71.7 % in the intervention group . This is an overall 22.8 % absolute increase ( p = 0.0001 ) , and 46.6 % relative increase in the delivery of preventive health services per patient in the intervention group compared to controls . Eight of thirteen preventive health services showed a statistically significant change ( p < 0.05 ) in favor of the intervention ( adjusted RR ( 95 % C.I. ) ) : counseling on brushing/flossing teeth ( 9.2 ( 4.3–19.6 ) ) , folic acid counseling ( 7.5 ( 2.7–20.8 ) ) , fecal occult blood testing ( 6.7 ( 1.9–24.1 ) ) , smoking cessation counseling ( 3.9 ( 2.2–7.2 ) ) , tetanus immunization ( 3.0 ( 1.7–5.2 ) ) , history of alcohol intake ( 1.33 ( 1.2–1.5 ) ) , history of smoking habits ( 1.28 ( 1.2–1.4 ) ) and blood pressure measurement ( 1.05 ( 1.00–1.10 ) ) . Conclusion This simple , low cost , clinical ly relevant intervention improves the delivery of preventive health services by prompting physicians of evidence -based recommendations in a checklist format that incorporates existing practice patterns . Periodic up date s of the Preventive Care Checklist Forms © will allow a feasible and easy-to-use tool for primary care physicians to provide evidence -based preventive health services to adults at routine health check-ups . The forms can also be incorporated into an electronic health record . The Preventive Care Checklist Forms © are accessible in English and French at the College of Family Physicians of Canada web site OBJECTIVE To determine the rates at which private primary -care clinics are recommending blood pressure and cholesterol measurement , smoking cessation , clinical breast examination , screening mammography , Papanicolaou testing , and influenza and pneumococcus immunizations . MATERIAL AND METHODS We conducted a mail survey of 7,997 r and omly selected patients from 44 primary -care clinics in and around Minneapolis-St . Paul , Minnesota , of whom 6,830 ( 85.4 % ) completed the question naire on preventive services delivery rates . The responses were analyzed statistically , including stratification by reason for the clinic visit . RESULTS On the average , about two-thirds of the patients in each clinic reported being up-to- date on preventive services before their clinic visit ; an exception was pneumococcus immunization ( mean rate , 33 % ) . Except for blood pressure and smoking cessation advice , less than 30 % of patients who were not up-to- date on a preventive service were offered it if the clinic visit was for a reason other than a checkup or physical examination . For patients who said that they saw their physician for a checkup or physical examination , the rate was more than 50 % only for Papanicolaou smear . In contrast , nearly all responding practitioners agreed that each of the eight preventive services was very important or important . CONCLUSION Preventive services consensus goals are not being met , even for patients who report that their clinic visit was for a checkup or physical examination . This finding suggests that it may be necessary to develop clinical systems that support and enable the delivery of preventive services OBJECTIVE To introduce the ASSUME study with the presentation of a clinical , socio-demographic , preventive and psychological profile of a geriatric population of patients who receive their health care in the General Internal Medicine Ambulatory Sector of our institution . METHODS The Assume study is a prospect i ve , r and omized trial which is directed at increasing the participation of patients in preventive health care strategies at a primary , secondary and tertiary level . In this paper we focus on the initial stage of the process which aims to define and synthesize predisposing risk factors in the geriatric patient which would be amenable to primary , secondary and tertiary preventive strategies . Through a process of patient interview profiles of a physical , social and psychological nature are have been constructed . With the availability of this profile a clearer definition of the potential benefit of preventive strategies could be established . In this paper we present the initial profile of patients of all patients r and omized to the study as of Sept. 01 , 1997 . RESULTS A total of 123 patients have been enrolled with 48(39 % ) males and 75(61 % ) females . The mean age of patients is 70 years with a median of 68 years . Cardiovascular disorders establish the leading disease events in our population of patients with Hypertension in 85 % , Ischemic heart disease in 50 % , Myocardial Infa rct ion in 19 % and 40 % with a history of Congestive Heart failure . Diabetes and Heart Failure were seen in 40 % . An average of 4.4 prescribed drugs per patient was documented . A minority of patients took more than 7 drugs and none took more than 9 medications . Most patients ( 67 or 55 % ) had not required hospitalizations in the preceding 12 months and none of the patients required more than 4 hospitalizations . The average LOS was 8.60 days . The Preventive Medicine profile reveals a large number of un-vaccinated adults . Regular cigarette smoking was seen in 12 % . We have used the body mass index as a measure of adequacy of weight . We highlight the number of patients who have a BMI equivalent to an obese , severely obese or morbidly obese category ( 41 % ) . The number of patients who follow a prescribed diet was found to be 54 patients for 44 % of the study group . With regards to the interventions primarily design ed for early cancer detecting , approximately half of the patients undergo the recommended annual screening interventions . The screening of visual accuracy was reported in 54 % , dental screen ( 24 % ) and auditory screening ( 15 % ) . Nearly a quarter of patients have severe depression . The CAPE testing reveal that in the information and orientation section most patients presented none or light dysfunction(87 % ) . In the conductual phase marked or severe impairment was detected in 12 % of patients . In the mental ability section 22 % of patients presented marked or severe impairment . CONCLUSION The geriatric population studied would benefit from modalities which would increment the modern modalities for primary and secondary prevention of disease . Follow-up studies will allow the evaluation of the effectiveness of the conceptual model proposed , which would increment the patient participation in these preventive modalities The objectives of this study were to : ( 1 ) study if an opportunistic screening of coronary heart disease ( CHD ) risk factors among male attenders in general practice ( GP ) influenced the overall subjective satisfaction with life of persons labelled ‘ high risk ’ compared to other screened persons ; ( 2 ) compare psychological well-being and patient satisfaction in a patient centred and self-directive ( PCSD ) intervention with conventional care ( CC ) ; and ( 3 ) evaluate patient satisfaction and psychological well-being among subjects with high CHD risk during a one year intervention study . Effects of ‘ labelling ’ were evaluated in 115 subjects with high CHD risk in comparison with a low risk reference population . The 22 participating GP centres were r and omly allocated to follow either a PCSD intervention or a CC approach . An overall satisfaction with life question was employed and psychological well-being were measured using the General Health Question naire ( 20 item version ) . Satisfaction measures on health care aspects were also included . No difference of change between the high risk and the reference population was found concerning satisfaction with life after screening . No significant difference of change was found within or between the PCSD and the CC group concerning emotional well-being or overall satisfaction with life during one year intervention . Satisfaction with the care received was significantly better in the CC group as compared with the PCSD group ( p=0.02 ) . Satisfaction with own efforts for improving health was , however , more pronounced in the PCSD group ( p=0.01 ) . A substantial number ( n=61 ) of the participants reported distaste of being reminded of the risk of heart disease and no more than 60 of the participants were satisfied with their own efforts for improving health . Although no significant change of satisfaction with life and emotional well-being due to screening or intervention could be detected , clinicians should be aware that encouraging patients to change life style may lead to patients ' annoyance of being reminded of the risk of disease and dissatisfaction with their own efforts . Increasing patient responsibility and self-determination may improve their satisfaction with their own efforts , but reduce satisfaction with medical care Aim : To analyze the consequence of preventive health screenings and discussion s on the utilization of secondary healthcare . Methods : All 30- to 49-year-old residents registered with a general practitioner in the district of Ebeltoft , Denmark , were included ( n=3,464 ) in a r and omized controlled trial with eight years ' follow-up . A r and om sample of 2,030 subjects was selected for invitation ( Invited ) . The remaining 1,434 persons were never contacted and served as external control group ( Non-Invited ) . Persons accepting participation were r and omly divided into one internal control group ( Question naire ) and two intervention groups . One intervention group was offered three health screenings ( Health Screening ) during the five years . The other intervention group were in addition offered a yearly health discussion with their general practitioner ( Health Screening and Discussion ) . Results : The rate ratio for hospital admissions was 0.97 ( 95 % confidence interval 0.80 to 1.18 ) in the Invited group compared with the Non-Invited . The annual admission rates showed a significant trend ( p=0.0003 ) with a decrease four and five years after intervention launch for the Invited group compared with the Non-Invited . A similar trend was found when comparing the internal control group with intervention groups ( p=0.0016 ) . Conclusions : A 30- to 49-year-old general population 's utilization of secondary healthcare did not increase in response to a general health promotion offer . During the observation period a significant decline in annual hospital admission rates was seen A study of hypertension in an industrial setting allowed us to confirm and explore an earlier retrospective finding that the labeling of patients as hypertensive result ed in increased absenteeism from work . After screening and referral , we found that absenteeism rose ( mean + /- 1 S.E. ) 5.2 + /- 2.3 days per year ( P less than 0.025 ) ; this 80 per cent increase greatly exceeded the 9 per cent rise in absenteeism in the general employee population during this period . The main factors associated with increased absenteeism were becoming aware of the condition ( P less than 0.01 ) and low compliance with treatment ( P less than 0.001 ) . Subsequent absenteeism among patients unaware of their hypertension before screening was not related to the degree of hypertension , whether the worker was started on therapy , the degree of blood-pressure control achieved or exposure to attempts to promote compliance . These results have major implication s for hypertension screening programs , especially since absenteeism rose among those previously unaware of their condition , regardless of whether antihypertensive therapy was begun BACKGROUND Decision-support information technology is often adopted to improve clinical decision making , but it is rarely rigorously evaluated . Congress m and ated the evaluation of Problem-Knowledge Couplers ( PKC Corp , Burlington , Vt ) , a decision-support tool proposed for the Department of Defense 's new health information network . METHODS This was a patient-level r and omized trial conducted at 2 military practice s. A total of 936 patients were allocated to the intervention group and 966 to usual care . Couplers were applied before routine ambulatory clinic visits . The primary outcome was quality of care , which was assessed based on the total percentage of any of 24 health care quality process measures ( opportunities to provide evidence -based care ) that were fulfilled . Secondary outcomes included medical re sources consumed within 60 days of enrollment and patient and provider satisfaction . RESULTS There were 4639 health care opportunities ( 2374 in the Coupler group and 2265 in the usual-care group ) , with no difference in the proportion of opportunities fulfilled ( 33.9 % vs 30.7 % ; P = .12 ) . Although there was a modest improvement in performance on screening/preventive measures , it was offset by poorer performance on some measures of acute care . Coupler patients used more laboratory and pharmacy re sources than usual-care patients ( logarithmic mean difference , 71 dollars ) . No difference in patient satisfaction was observed between groups , and provider satisfaction was mixed . CONCLUSION This study provides no strong evidence to support the utility of this decision-support tool , but it demonstrates the value of rigorous evaluation of decision-support information technology BACKGROUND The U.S. Congress m and ated evaluations , initiated in 1989 , to determine whether extending Medicare benefits to include preventive services would improve health status , reduce costs of care , and improve health risk behaviors of beneficiaries . METHODS The Johns Hopkins Medicare Preventive Services Demonstration was a r and omized trial in which Medicare beneficiaries were assigned either to an intervention group that was offered yearly preventive visits for 2 years and optional counseling visits to their primary care provider or to a control group that received usual care . This report describes the effect of the intervention over a period of 2 years on smoking , problem alcohol use , and sedentary lifestyle . RESULTS Differences were observed between the intervention and control groups in the extent to which changes occurred in smoking and problem alcohol use , but none of the differences was statistically significant . The proportion of smokers who quit was higher in the intervention group than in the control group ( 24.2 vs 17.9 % , P = 0.09 ) . However , a higher proportion of problem drinkers in the control group improved ( 67.1 vs 57.0 % , P = 0.183 ) . There was virtually no difference between the intervention and the control groups in the proportion with improvement in sedentary lifestyle . CONCLUSIONS This study demonstrates the difficulty of bringing about health behavior change in older patients in the course of a yearly preventive visit for 2 years with their primary care physician when the visit encompasses screening and immunizations , as well as health behavior counseling directed by the physician . Further study is required to determine whether a more intense program of counseling for health behavior change among older persons by their primary care providers would be effective While most intervention studies on coronary heart disease have focused on the high-risk person only , the present study used the family as the unit of intervention . In the study 1373 high-risk men , ages 30 - 54 years , were identified on the basis of high total cholesterol ( TC ) and /or low relative high-density lipoprotein cholesterol ( HDL-C ) ( HDL-C/TC ) following the 1979/1980 survey in Tromsø . The men and their families were r and omly allocated to a control or intervention condition . The intervention families were given advice on diet , smoking , and exercise . At rescreening in 1986/1987 , significantly lower risk factor levels were found in both the intervention men and their spouses compared with those in the control group . For children , the differences were small and mostly nonsignificant . Men , spouses , and children in the intervention group reported more favorable dietary habits than those in the control group . No differences were found in smoking or leisure time physical activity Background There is a debate on whether preventive home visits to older people have any impact . This study was undertaken to investigate whether preventive home visits by professional health workers to older persons can postpone mortality in a Swedish context . Method A controlled trial in a small community in the north of Sweden . Participants are healthy pensioners aged 75 years and over . 196 pensioners were selected as the intervention group and 346 as the control group . The intervention , two visits per year , lasted two years . Results During the intervention , mortality was 27 per 1000 in the intervention group and 48 per 1000 in the control group . The incidence rate ratio for the control group IR2000–2001 was 1,79 ( 95%CI = 0,94–3,40 ) . Analysing the data with an " on treatment approach " gave a significant result , 2,31 ( 95%CI = 1,07–5,02 ) After the trial the difference between the groups disappeared . Conclusion Preventive home visits in a healthy older population can postpone mortality in a Swedish context if they are carried out by professional health-workers in a structured way . When the home visit programme ended the effect on mortality disappeared . These findings are dependent on context ual factors that make it difficult to form general policy recommendations Abstract Objective : To determine the effectiveness of health checks , performed by nurses in primary care , in reducing risk factors for cardiovascular disease and cancer . Design : R and omised controlled trial . Setting : Five urban general practice s in Bedfordshire . Subjects : 2205 men and women who were r and omly allocated a first health check in 1989 - 90 and a re-examination in 1992 - 3 ( the intervention group ) ; 1916 men and women who were r and omly allocated an initial health check in 1992 - 3 ( the control group ) . All subjects were aged 35 - 64 at recruitment in 1989 . Main outcome measures : Serum total cholesterol concentration , blood pressure , body mass index , and smoking prevalence ( with biochemical validation of cessation ) ; self reported dietary , exercise , and alcohol habits . Results : Mean serum total cholesterol was 3.1 % lower in the intervention group than controls ( difference 0.19 mmol/l ( 95 % confidence interval 0.12 to 0.26 ) ; in women it was 4.5 % lower ( P<0.0001 ) and in men 1.6 % ( P<0.05 ) , a significant difference between the sexes ( P<0.01 ) . Self reported saturated fat intake was also significantly lower in the intervention group . Systolic and diastolic blood pressures and body mass index were respectively 1.9 % , 1.9 % , and 1.4 % lower in the intervention group ( P<0.005 in all cases ) . There was a 3.9 % ( 2.4 to 5.3 ) difference in the percentage of subjects with a cholesterol concentration > /=8 mmol/l , but no significant differences in the number with diastolic blood pressure > /=100 mm Hg or body mass index > /=30 kg/m2 . There was no significant difference between the two groups in prevalence of smoking or excessive alcohol use . Annual rechecks were no more effective than a single recheck at three years , but health checks led to a significant increase in visits to the nurse according to patients ' degree of cardiovascular risk . Conclusions : The benefits of health checks were sustained over three years . The main effects were to promote dietary change and reduce cholesterol concentrations ; small differences in blood pressure may have been attributable to accommodation to measurement . The benefits of systematic health promotion in primary care are real , but must be weighed against the costs in relation to other priorities . Key messages Key messages There is little effect on smoking or alcohol use , and more targeted approaches to modifying these behaviours may be appropriate Systematic implementation of health checks might lead to a reduction in risk of myocardial infa rct ion among those who attend of about 5 - 15 % ; men , who are at higher risk , show less change than women Health checks consume substantial re sources , and their effect is attenuated by non-attendance The benefits of health promotion through primary care must be weighed against their costs and in relation to other Background The increasing prevalence of type 2 diabetes poses a major public health challenge . Population -based screening and early treatment for type 2 diabetes could reduce this growing burden . However , the benefits of such a strategy remain uncertain . Methods and design The ADDITION-Cambridge study aims to evaluate the effectiveness and cost-effectiveness of ( i ) a stepwise screening strategy for type 2 diabetes ; and ( ii ) intensive multifactorial treatment for people with screen-detected diabetes in primary care . 63 practice s in the East Anglia region participated . Three undertook the pilot study , 33 were allocated to three groups : no screening ( control ) , screening followed by intensive treatment ( IT ) and screening plus routine care ( RC ) in an unbalanced ( 1:3:3 ) r and omisation . The remaining 27 practice s were r and omly allocated to IT and RC . A risk score incorporating routine practice data was used to identify people aged 40–69 years at high-risk of undiagnosed diabetes . In the screening practice s , high-risk individuals were invited to take part in a stepwise screening programme . In the IT group , diabetes treatment is optimised through guidelines , target-led multifactorial treatment , audit , feedback , and academic detailing for practice teams , alongside provision of educational material s for newly diagnosed participants . Primary endpoints are modelled cardiovascular risk at one year , and cardiovascular mortality and morbidity at five years after diagnosis of diabetes . Secondary endpoints include all-cause mortality , development of renal and visual impairment , peripheral neuropathy , health service costs , self-reported quality of life , functional status and health utility . Impact of the screening programme at the population level is also assessed through measures of mortality , cardiovascular morbidity , health status and health service use among high-risk individuals . Discussion ADDITION-Cambridge is conducted in a defined high-risk group accessible through primary care . It addresses the feasibility of population -based screening for diabetes , as well as the benefits and costs of screening and intensive multifactorial treatment early in the disease trajectory . The intensive treatment algorithm is based on evidence from studies including individuals with clinical ly diagnosed diabetes and the education material s are informed by psychological theory . ADDITION-Cambridge will provide timely evidence concerning the benefits of early intensive treatment and will inform policy decisions concerning screening for type 2 diabetes . Trial registration Current Controlled trials IS RCT A neuropsychological screening battery including the Mini-Mental State Examination and four other brief cognitive tests ( Russell 's Adaptation of the Visual Reproduction Test , Trail Making Test , Verbal Fluency Tests on letters and category , and the Buschke Selective Reminding Test ) was administered to a r and omly selected population sample of 403 subjects aged 68 to 77 years to evaluate the effect of education , age , and sex on test scores . The difference in neuropsychological screening tests between various education groups ( 3 years or less , 4 to 6 years , 7 years or more ) was statistically highly significant , even after the adjustment for the effect of age . The subscores and total scores were lowest in the minimal education group on every neuropsychological test . Education correlated more strongly than age with all neuropsychological test scores and subscores . The effect of sex on test results was seen only in some subscores of brief neuropsychological tests but not in a single item of the Mini-Mental State Examination . On the basis of our results , the effects of education , age , and sex have to be evaluated before using brief neuropsychological tests in population -based dementia screening . ( J Geriatr Psychiatry Neurol 1992;5:162–171 ) In a gerontological field- study in Cologne , West-Germany , 1114 subjects of a r and om sample of elderlies were successively offered three modalities for a medical check-up , which covered a physical examination and a psychiatric interview : 1 . in the out-patient department of a psychiatric hospital ( Rheinische L and esklinik Köln ) ( 38 % of the subjects ) ; 2 . in the subjects ' home by a psychiatrist of the hospital ( 13 % ) ; 3 . by having the general practitioner fill out a question naire ( 21 % ) . There remained a fourth group of subjects who refused any medical check-up ( 28 % ) . Data on social and economic problems had been obtained for all subjects in a preceding interview . These data were used to find out to what extent selection mechanisms were effective . Results indicate that to a certain extent the modality of the medical check-up chosen by the subject is related to some of the variables analyzed BACKGROUND Preventive assessment of prevalent disorders may be considered as an instrument to maintain independence in the elderly . However , the outcomes of studies on these types of screening differ considerably regarding their effects . OBJECTIVES The aim of the present study was to assess the effects of GPs ' screening of the elderly on four highly prevalent disorders with possibilities for treatment : hearing and visual disorders , urinary incontinence and mobility disorders . METHODS In an intervention study in 12 general practice s , 1121 subjects aged 75 years and over were screened . R and omization was done by practice into an intervention group ( 576 ) and a control group ( 545 ) . In the intervention group , all elderly patients were screened for the four disorders during the first year of the study . When the GP and patient agreed on intervention , usual care was provided by the GP . The patients in the control group were not screened in the first year . In the second year , all patients in both groups were screened for the four disorders . RESULTS For none of the four disorders was a measurable effect of the screening at the population level found . In the first year , 1013 new disorders were found involving 479 of 576 people . The GPs considered information to be new in 293 cases . In 245 cases ( out of 293 ) , the GP discussed the new information with the patient . Of the 89 cases in which the patient agreed with an intervention , improvement was reported in 17 cases . CONCLUSIONS Implementing a st and ardized screening programme for four highly prevalent disorders for elderly people is not recommended . Preventive assessment of the elderly should be applied in ways other than by screening . Preventive care should pay attention to the individual needs of the elderly , should be started before the age of 75 years and should be offered in a flexible way We have assessed the acceptability of a method for screening for risk of future hip fracture in elderly women . After receipt of an initial response to a mailed risk-factor question naire sent out to 5,306 women , women were r and omly assigned to active or control groups . The active group was invited to participate in a screening visit that comprised a life-style question naire and a quantitative ultrasound heel scan . General practitioners ( GPs ) of women who were found to be in the lowest quartile of broadb and ultrasound attenuation and /or who had two or more risk factors for hip fracture were advised to prescribe a calcium and vitamin D supplement . A second mailed question naire was sent to both groups 1 to 3 years later . Compared with the control group , the active group had a 56 % lower risk of fracture ( odds ratio [ OR ] , 0.44 ; 95 % confidence interval [ CI ] , 0.24–0.81 adjusted age , weight , and treatment status ) . At follow-up , the proportion of fallers in the active group ( 25.3 % ) was lower than that in the control group ( 29.6 % ) ( P = 0.064 ) . The control group was found to have a higher rate of falls at follow-up than the active group ( 95 % CI , 0.02–0.22 ) ; no difference was found at baseline ( 95 % CI , −0.08 to + 0.14 ) . The screening method used was found to be acceptable to the majority of elderly women in this study . Screening the elderly in this way together with simple advice on treatment appears to reduce the age-associated increase in fall rates and the number of subsequent fractures . This form of screening may provide a cost-effective method to reduce falls and fractures in free-living elderly women . However , no such cost-effectiveness analysis has been performed to date The results of a four year demonstration project of preventive services for Medicare managed care enrollees suggest that health promotion programs can impact health behaviors and outcomes . The study provided selected preventive services to 1,800 Medicare enrollees in a managed care environment . Participants were r and omly assigned to control and experimental groups with the experimental group receiving an intervention service package and the control group usual care . The results included enhanced health behavior practice s , lower depression , and higher immunization rates among those individuals in the experimental group . This study suggests that selected preventive services can be provided in a managed care environment to Medicare enrollees with likely positive health status and utilization outcomes BACKGROUND In a r and omized trial evaluating preventive services for older adults excess mortality was observed in the treatment group . We examined four explanations : unbalance of baseline characteristics , unintended effects of the intervention , consequence of an autonomy intervention ( including increased number of living wills in the treatment group ) , and chance . We focus here on the effects of the autonomy intervention . METHODS Preparation of living wills in the treatment and control groups was compared both at baseline and follow-up . A linear predictor of mortality was used to identify participants at high risk of dying . Charts of these 200 participants were review ed for evidence of serious medical events and resuscitation decisions . Rates of life-sustaining treatment were compared between treatment and controls using logistic regression . RESULTS More living wills ( 65 % ) were noted for the treatment group than control group ( 47 % ) at follow-up . Thirty-six per cent of participants were identified as having a serious medical event ; of these , participants in the treatment group were over twice as likely not to receive life-sustaining treatment . CONCLUSIONS Advance directives contributed to excess deaths , indicating the success of the autonomy intervention Objectives : Older immigrants from non-industrialised countries are a growing group , they have comparatively many health problems and are often hard to reach through health promotion and other preventive services . The aim of this study was to assess the effect of a short health education and physical exercise programme on the health and the physical activity of Turkish first generation elderly immigrants . Design : R and omised controlled trial . Setting : Welfare services in six Dutch cities . Participants : 126 people born in Turkey and aged 45 years and over , of whom 92 completed the trial . Intervention : Eight , two hour sessions consisting of health education and exercises . Topics in health education focused on means to maintain a good health . Education was adapted to the culture and knowledge of older Turks and offered by a Turkish peer educator , in Turkish . Main outcome measures : Physical and mental wellbeing , and mental health based on the SF-12/36 ; knowledge on health and disease ; physical activity . Results : Participants were highly disadvantaged ; 52 % had not completed primary school and 49 % had considerable problems in speaking Dutch . Participants in the intervention group showed an improvement in mental health ( effect size : 0.38 SD ( 95 % confidence intervals 0.03 to 0.73 ) , p=0.03 ) ; the oldest subgroup also in mental wellbeing ( effect size 0.75 SD ( 0.22 to 1.28 ) , p=0.01 ) . No improvements were seen in physical wellbeing and activity , nor in knowledge . Conclusions : Health education and physical exercise improve the mental state of deprived immigrants . Painstaking cultural adaptations to contents and method of delivery are essential to reach this effect Results are reported from a trial of multifactorial prevention of coronary heart disease ( CHD ) in occupational groups , involving r and omization of 66 factories to intervention and control ( 49,781 men ages 40 to 59 ) in the United Kingdom , Belgium , Italy , and Pol and . Net average reductions in the intervention factors were 1.2 % ( plasma cholesterol ) , 8.9 % ( daily cigarettes ) , 0.4 % ( weight ) , 2 % ( systolic blood pressure ) , and 11 % for a combined risk estimate . Reductions were larger in high-risk men ( 19 % for the combined estimate ) . Red blood cell fatty acid profiles were substantially changed . There was a net overall reduction of 7.4 % in fatal CHD and 2.7 % in total deaths . Benefits were larger in centers achieving larger risk factor reductions , and in one country -- Belgium -- the net decreases in CHD incidence and total deaths were significant at the 5 % level . Benefit was at least as great in men with established ECG abnormality . It is concluded that CHD risk in middle-aged men seems to be reducible by simple and cost-effective means Medicare beneficiaries enrolled in a health maintenance organization ( HMO ) were r and omized to a preventive services benefit package for 2 years or to usual care . At 24- and 48-month followups , the treatment group had completed more advance directives , participated in more exercise , and consumed less dietary fat than the control group . Unexpectedly , more deaths occurred in the treatment group . Surviving treatment-group enrollees reported higher satisfaction with health , less decline in self-rated health status , and fewer depressive symptoms than surviving control participants . Despite these changes , the intervention did not yield lower cost per quality -adjusted life year in this historically prevention-oriented HMO The study describes changes in cardiovascular risk factors during 10 years of a community intervention program conducted in a rural area in Central Italy . Two areas were involved , one for treatment and one for reference . In 1983 - 84 , 739 men and 859 women in the treatment area and 942 men and 1045 women in the control area , aged 20 - 69 years , were screened ; total and HDL cholesterol , systolic and diastolic blood pressure , fasting blood glucose , smoking habit , weight and height were measured . Between 1983 and 1993 several intervention activities based on community medicine were carried out in the treatment area . They were based on interaction with the local socio-sanitary institutions and school system in order to influence individual persons , small groups and entire community . Major effort was addressed to mass health education , nutrition education , antismoking-propag and a and detection and treatment of hypertension , diabetes and hyperlipidemia INTRODUCTION Self-reported health has been shown to predict mortality . We lack knowledge on whether a lifestyle intervention can improve self-reported mental and physical health in a general population . METHODS Inter99 , Denmark ( 1999 - 2006 ) is a r and omised population -based intervention study . We screened for ischemic heart disease and repeatedly offered advice and assistance to obtain a healthier lifestyle . Health related quality of life was measured by Short Form 12 ( SF-12 ) ; completed by 9322 at baseline and 7719 at five-year follow-up . In linear mixed models we investigated the effect of the intervention on self-reported health over time . RESULTS At baseline men had higher physical health-component scores ( PCS ) than women . Living with a partner , being employed , and being healthy was associated with high PCS . The mental health-component scores ( MCS ) showed the same socio-demographic differences , except that MCS increased with age . Significantly fewer participants in the intervention groups had decreased their PCS and MCS compared with the control group . Adjusted multilevel analyses confirmed that the intervention significantly improved physical- ( p=0.008 ) and mental health ( p<0.001 ) over time compared with the control group . CONCLUSION Screening for ischemic heart disease and offering lifestyle intervention had a significantly beneficial effect on mental and physical self-reported health in the long term in a general population Background and aims : Programs of preventive home visits for ambulatory housebound elders have not yet become established in Japan . The aim of this r and omized pilot study was to investigate effects of such visits by public health nurses in Japan . Methods : A r and omized controlled study with 18-month follow-up was conducted in a small Japanese agricultural town . Participants ( n=119 ) were ambulatory housebound elders aged 65 and over , who were able to walk but who went outdoors less than three times a week at baseline survey . They were r and omly assigned to intervention ( n=59 ) or control group ( n=60 ) . Intervention group subjects received preventive home visits by public health nurses over 18 months ( mean home visits=4.3 ) . Control group subjects received usual primary and community care . Activities of daily living ( ADLs ) , functional capacity , self-efficacy for daily activities , self-efficacy for health promotion , depression , and social support were collected via question naire at baseline and at the 18-month follow-up point . Results : At follow-up , 81.4 % of intervention group subjects were still living at home vs 73.3 % of control group subjects ( NS ) . Simple group comparisons following repeated measures ( ANCOVA ) showed that the intervention group had higher ADL scores than the control group at follow-up ( p=0.044 ) . Conclusions : These pilot results suggest that home visits by public health nurses may be effective in helping to reduce ADL decline among ambulatory housebound elders Aim : To compare the effects of information pamphlets with those of group counselling on cardiovascular risk among individuals from a community with low socioeconomic status . Methods : Risk factors for coronary heart disease were assessed in 1131 men and women from a community with low socioeconomic status in suburban Melbourne . Individuals deemed to be at moderate risk , on the basis of an integrated risk score greater than 65 , were asked to participate in a r and omized trial comparing two simple interventions design ed to reduce cardiovascular risk . One hundred and sixty-four individuals were r and omly assigned to group A ( n = 85 ) and participated in a single group counselling session lasting between 1.5 and 2.0 h. Group B ( n = 79 ) received a specially prepared pamphlet that provided brief written information concerning risk-factor modification . Both groups were asked to attend a follow-up assessment of risk factors 3 and 6 months after entry . Results : There was no significant difference in the change in risk-factor levels between those receiving information pamphlets and those attending the group counselling session after 3 or 6 months of follow-up . Small but significant decreases ( P < 0.05 ) were seen in systolic and diastolic blood pressures ( −−5/4 mmHg for group A , −−5/3 mmHg for group B ) , total plasma cholesterol level ( −−0.30 mmol/l for groups A and B ) and overall coronary risk score ( −14.4 and −13.9 for groups A and B , respectively ) . Body weight remained unchanged during the study period in both groups . Conclusion : Screening together with 1.5−2 h group counselling had no more influence on cardiovascular risk factors than screening together with provision of information pamphlets in a population with low socioeconomic status In a prospect i ve study of 7735 middle-aged men , both current and ex-cigarette-smokers had a risk of a major IHD event , within an average 6.2 years of screening , more than twice that in men who had never smoked cigarettes ; men who had given up smoking more than 20 years ago still had an increased risk . This excess risk among ex-smokers is only to a small extent explained by their higher blood pressure , serum total cholesterol , and body-mass index . An increased prevalence of IHD in men who had recently given up smoking also made a small contribution to excess risk . In both current and former cigarette smokers , the number of years a man had smoked cigarettes ( " smoking-years " ) was the clearest indicator of IHD risk due to cigarettes . The major benefit of giving up smoking may lie in halting the accumulation of smoking years The Oxford and Collaborators Health CHECK Trial ( OXCHECK ) was a r and omized controlled trial of the effectiveness of nurse-administered health checks in the general practice setting . It was design ed primarily to influence risk factors for cardiovascular disease and cancer . The fourth and final year has now been completed , and the data analysis on over 8,100 health checks is under way . The findings from Year I have not been very encouraging in terms of lifestyle changes in moderate risk groups . This article briefly describes the design and methodology of the project , but mainly focuses on the practical issues involved in performing the health checks and on how the nurses and patients have felt about participating in the project . Much has happened to general practice , health promotion and the economy since the inception of OXCHECK in 1988 . The OXCHECK nurses have experienced a variety of responses and attitudes from patients . These are significant insomuch as they may provide a rationale for design ing alternative methods of assessing lifestyle change and individuals ' perception of risk . The importance of providing a strong link between the academic department involved in the project and the local clinical practice s will be discussed in the context of other key facilitating roles . However , the appropriateness of promoting certain preventive measures in the general practice setting can also be question ed Abstract Two quite different approaches have been taken to the evaluation of screening programs in the Health Insurance Plan of New York ( HIP ) . In one , a highly specific end result is at issue . The central question in this project is whether periodic screening with mammography and clinical examination of the breast results in a reduction in mortality from breast cancer in the female population . The project is being conducted as a r and omized clinical trial with study and control groups selected from the enrolled population of HIP . Of 31,000 study group women contacted , 20,200 , or 65 % participated in at least one examination . The other study is concerned with whether the impact of a multiple array of services , automated multiphasic health testing , and follow-up paramedical and medical services , on health status and health care behavior is greater among the poor than the rest of the population . The results of the breast cancer study provide clear evidence that over the short run period of 5 years of follow-up , the study women have about one-third lower mortality from breast cancer than the controls . Reduction in breast cancer mortality was found at ages 50 and over but not at ages 40–49 years . In the multiphasic health testing study , preliminary analysis of the data confirms one of the initial assumptions of the study , i.e. that a significant gap exists between the poverty and nonpoverty groups in the occurrence of health problems . A higher proportion of the poverty group reported a health complaint or specific condition . The study indicated that this group was also likely to report these problems with greater frequency and greater severity of the complaints Objective To evaluate the effectiveness of the community based Cardiovascular Health Awareness Program ( CHAP ) on morbidity from cardiovascular disease . Design Community cluster r and omised trial . Setting 39 mid-sized communities in Ontario , Canada , stratified by location and population size . Participants Community dwelling residents aged 65 years or over , family physicians , pharmacists , volunteers , community nurses , and local lead organisations . Intervention Communities were r and omised to receive CHAP ( n=20 ) or no intervention ( n=19 ) . In CHAP communities , residents aged 65 or over were invited to attend volunteer run cardiovascular risk assessment and education sessions held in community based pharmacies over a 10 week period ; automated blood pressure readings and self reported risk factor data were collected and shared with participants and their family physicians and pharmacists . Main outcome measure Composite of hospital admissions for acute myocardial infa rct ion , stroke , and congestive heart failure among all community residents aged 65 and over in the year before compared with the year after implementation of CHAP . Results All 20 intervention communities successfully implemented CHAP . A total of 1265 three hour long sessions were held in 129/145 ( 89 % ) pharmacies during the 10 week programme . 15 889 unique participants had a total of 27 358 cardiovascular assessment s with the assistance of 577 peer volunteers . After adjustment for hospital admission rates in the year before the intervention , CHAP was associated with a 9 % relative reduction in the composite end point ( rate ratio 0.91 , 95 % confidence interval 0.86 to 0.97 ; P=0.002 ) or 3.02 fewer annual hospital admissions for cardiovascular disease per 1000 people aged 65 and over . Statistically significant reductions favouring the intervention communities were seen in hospital admissions for acute myocardial infa rct ion ( rate ratio 0.87 , 0.79 to 0.97 ; P=0.008 ) and congestive heart failure ( 0.90 , 0.81 to 0.99 ; P=0.029 ) but not for stroke ( 0.99 , 0.88 to 1.12 ; P=0.89 ) . Conclusions A collaborative , multi-pronged , community based health promotion and prevention programme targeted at older adults can reduce cardiovascular morbidity at the population level . Trial registration Current controlled trials IS RCT N50550004 OBJECTIVE Can indicative prevention of home-visiting nurses be effective when targeted at a frail senior population using multidimensional geriatric assessment s and personalized care plans ? METHODS We performed an individually r and omized controlled trial in 33 blinded primary care practice s over 18 months . The 651 participants were aged 75 years or older , lived at home , and were frail but neither terminally ill nor demented . A score in the lowest quartile on at least two of six self-reported functional health domains ( COOP-WONCA charts ) , defined frail health . We compared usual care with proactive home visits by trained community nurses . The nurses ( a ) assessed the care needs with a multidimensional computerized geriatric instrument , which enabled direct identification of health risks ; ( b ) determined care priorities together with the person ; ( c ) design ed and executed individually tailored interventions ; and ( d ) monitored participants by telephone and on average three home visits . Primary outcome measures were functional health and instrumental activities of daily living disability . Secondary outcomes were acute hospital admittance ( time until ) , institutionalization , and mortality . RESULTS We found no significant differences between intervention and usual care group on any of the outcome measures . Predefined subgroup analyses revealed a higher risk of hospital admission for persons with poor health in the intervention group . CONCLUSIONS We could not demonstrate preventive effects of home visits by nurses in vulnerable older persons . Hospital admissions increased in the frailest group . The search for effective interventions for vulnerable persons requires further investigation . Future efforts may focus on improved integrated approaches BACKGROUND Prophylactic strategies to counter acquired hearing impairment may involve routine audiometric screening of asymptomatic working-age adults attending general practice for regular health checks . AIM To evaluate the effect of adult hearing screening on subsequent noise exposure and hearing . DESIGN OF STUDY A r and omised controlled population -based study of health checks and health discussion s in general practice . SETTING The project was initiated in the district of Ebeltoft , Aarhus county , Denmark . METHOD Intervention group participants ' hearing thresholds were determined audiometrically at 0.5 , 1 , 2 , 3 , and 4 kHz in each ear . Participants were advised to get their ears checked if the average hearing loss exceeded 20 dB hearing level ( dBHL ) in either ear . Noise avoidance was emphasised when thresholds exceeded 25 dBHL bilaterally at 4 kHz . Follow-up included question naires and audiometry . RESULTS Hearing loss was observed among 18.9 % of the study sample at baseline . At the five-year follow-up we recorded no significant differences between the control and the intervention groups regarding subjective or objective hearing , or exposure to occupational noise . However , there was a tendency towards reduction in exposure to leisure noise among intervention participants ( P = 0.045 ) . Approximately 20 % reported hearing problems ; 16.5 % reported tinnitus-related complaints ; 0.8 % used hearing aids ; 35.0 % reported frequent noise exposure ; and occluding wax was suspected in 2.1 % . CONCLUSION Preventive health checks with audiometry did not significantly affect hearing , but leisure noise exposure tended to become less frequent . The poor effect may be ascribed to inadequate audiological counselling or a higher priority to other advice , e.g. on cardiovascular risk or lifestyle Abstract Objective : To assess the long term effectiveness of the “ green prescription ” programme , a clinician based initiative in general practice that provides counselling on physical activity . Design : Cluster r and omised controlled trial . Practice s were r and omised before systematic screening and recruitment of patients . Setting : 42 rural and urban general practice s in one region of New Zeal and . Subjects : All sedentary 40–79 year old patients visiting their general practitioner during the study 's recruitment period . Intervention : General practitioners were prompted by the patient to give oral and written advice on physical activity during usual consultations . Exercise specialists continued support by telephone and post . Control patients received usual care . Main outcome measures : Change in physical activity , quality of life ( as measured by the “ short form 36 ” ( SF-36 ) question naire ) , cardiovascular risk ( Framingham and D'Agostino equations ) , and blood pressure over a 12 month period . Results : 74 % ( 117/159 ) of general practitioners and 66 % ( 878/1322 ) of screened eligible patients participated in the study . The follow up rate was 85 % ( 750/878 ) . Mean total energy expenditure increased by 9.4 kcal/kg/week ( P=0.001 ) and leisure exercise by 2.7 kcal/kg/week ( P=0.02 ) or 34 minutes/week more in the intervention group than in the control group ( P=0.04 ) . The proportion of the intervention group undertaking 2.5 hours/week of leisure exercise increased by 9.72 % ( P=0.003 ) more than in the control group ( number needed to treat=10.3 ) . SF-36 measures of self rated “ general health , ” “ role physical , ” “ vitality , ” and “ bodily pain ” improved significantly more in the intervention group ( P<0.05 ) . A trend towards decreasing blood pressure became apparent but no significant difference in four year risk of coronary heart disease . Conclusion : Counselling patients in general practice on exercise is effective in increasing physical activity and improving quality of life over 12 months . What is already known on this topic Counselling patients in general practice on exercise has result ed in gains in physical fitness and activity , but no health benefits have been found What this study adds Counselling patients in general practice on exercise is effective in increasing physical activity and improving quality of life over 12 months without evidence of adverse effects The intervention may reduce blood pressure by an average of 1–2 mm Hg over 12 months No changes in the risk of coronary heart disease were observed The intervention is sustainable in usual general practice Prompting practice staff to deliver the intervention may have increased its Background Worldwide , type 2 diabetes ( T2DM ) prevalence has more than doubled over two decades . In Australia , diabetes is the second highest contributor to the burden of disease . Lifestyle modification programs comprising diet changes , weight loss and moderate physical activity , have been proven to reduce the incidence of T2DM in high risk individuals . As part of the Council of Australia Governments , the State of Victoria committed to develop and support the diabetes prevention program ‘ Life ! Taking action on diabetes ’ ( Life ! ) which has direct lineage from effective clinical and implementation trials from Finl and and Australia . The Melbourne Diabetes Prevention Study ( MDPS ) has been set up to evaluate the effectiveness and cost-effectiveness of a specific version of the Life ! program . Methods / design We intend to recruit 796 participants for this open r and omized clinical trial ; 398 will be allocated to the intervention arm and 398 to the usual care arm . Several methods of recruitment will be used in order to maximize the number of participants . Individuals aged 50 to 75 years will be screened with a risk tool ( AUSDRISK ) to detect those at high risk of developing T2DM . Those with existing diabetes will be excluded . Intervention participants will undergo anthropometric and laboratory tests , and comprehensive surveys at baseline , following the fourth group session ( approximately three months after the commencement of the intervention ) and 12 months after commencement of the intervention , while control participants will undergo testing at baseline and 12 months only . The intervention consists of an initial individual session followed by a series of five structured-group sessions . The first four group sessions will be carried out at two week intervals and the fifth session will occur eight months after the first group session . The intervention is based on the Health Action Process Approach ( HAPA ) model and sessions will empower and enable the participants to follow the five goals of the Life ! program . Discussion This study will determine whether the effect of this intervention is larger than the effect of usual care in reducing central obesity and cardiovascular risk factors and thus the risk of developing diabetes and cardiovascular disease . Also it will evaluate how these two options compare economically . Trial registration Australian New Zeal and Clinical Trials Registry Background The search for preventive methods to mitigate functional decline and unwanted relocation by older adults living in the community is important . Preventive home visit ( PHV ) models use infrequent but regular visits to older adults by trained practitioners with the goal of maintaining function and quality of life . Evidence about PHV efficacy is mixed but generally supportive . Yet interventions have rarely combined a comprehensive ( biopsychosocial ) occupational therapy intervention protocol with a home visit to older adults . There is a particular need in the USA to create and examine such a protocol . Methods / Design The study is a single-blind r and omized controlled pilot trial design ed to assess the feasibility , and to obtain preliminary efficacy estimates , of an intervention consisting of preventive home visits to community-dwelling older adults . An occupational therapy-based preventive home visit ( PHV ) intervention was developed and is being implemented and evaluated using a repeated measures design . We recruited a sample of 110 from a population of older adults ( 75 + ) who were screened and found to be at-risk for functional decline . Participants are currently living in the community ( not in assisted living or a skilled nursing facility ) in one of three central North Carolina counties . After consent , participants were r and omly assigned into experimental and comparison groups . The experimental group receives the intervention 4 times over a 12 month follow-up period while the comparison group receives a minimal intervention of mailed printed material s. Pre- and post-intervention measures are being gathered by question naires administered face-to-face by a treatment-blinded research associate . Key outcome measures include functional ability , participation , life satisfaction , self-rated health , and depression . Additional information is collected from participants in the experimental group during the intervention to assess the feasibility of the intervention and potential modifiers . Fidelity is being addressed and measured across several domains . Discussion Feasibility indications to date are positive . Although the protocol has some limitations , we expect to learn enough about the intervention , delivery and effects to support a larger trial with a more stringent design and enhanced statistical power . Trial Registration Clinical Trials.gov ID BACKGROUND Uncertainties persist concerning the effects of early intensive management of type 2 diabetes and which patients benefit most from such an approach . AIM To describe change in modelled cardiovascular risk in the 14 months following diagnosis , and to examine which baseline patient characteristics and treatment components are associated with risk reduction . DESIGN AND SETTING A cohort of individuals from a pragmatic , single-blind , cluster-r and omised controlled trial of 236 females and 361 males with screen-detected type 2 diabetes and without prior cardiovascular disease ( CVD ) , from 49 GP surgeries in eastern Engl and , examined at baseline ( 2002 - 2006 ) and after 14-months ' follow-up . METHOD Multiple linear regression was used to quantify the association between baseline patient characteristics , treatment components , and change in modelled 10-year cardiovascular risk ( UK Prospect i ve Diabetes Study [ UKPDS ] [ version 3 ] risk engine ) . RESULTS There was a downward shift in the distribution of modelled CVD risk over 14 months mean 31 % ( st and ard deviation [ SD ] = 14 % ) to 26 % [ SD = 13 % ] ) . Older individuals , males , and those with a larger waist circumference at baseline exhibited smaller risk reductions . Individuals prescribed higher numbers of drugs over the follow-up period , and those who decreased their energy intake or reduced their weight , demonstrated larger reductions in modelled risk . CONCLUSION It is possible to achieve significant reductions in modelled CVD risk over 14 months following diagnosis of diabetes by screening . Risk reduction appeared to be driven mainly by prescription of higher numbers of drugs , decreased energy intake , and weight reduction . There was room for further risk reduction , as many patients were not prescribed recommended treatments BACKGROUND AND PURPOSE Stroke has been the second leading cause of death in large cities in China since the 1980s . Meanwhile , the prevalences of hypertension and smoking have steadily increased over the last 2 decades . Therefore , a community-based intervention trial was initiated in 7 Chinese cities in 1987 . The overall goal of the study was to evaluate the effectiveness of an intervention aim ed at reducing multiple risk factors for stroke . The primary study objective was to reduce the incidence of stroke by 25 % over 3.5 years of intervention . METHODS In May 1987 in each of 7 the cities , 2 geographically separated communities with a registered population of about 10 000 each were selected as either intervention or control communities . In each community , a cohort containing about 2700 subjects ( > /=35 years old ) free of stroke was sample d , and a survey was administered to obtain baseline data and screen the eligible subjects for intervention . In each city , a program of treatment for hypertension , heart disease , and diabetes was instituted in the intervention cohort ( n approximately 2700 ) and health education was provided to the full intervention community ( n approximately 10 000 ) . A follow-up survey was conducted in 1990 . Comparisons of intervention and control cohorts in each city were pooled to yield a single summary . RESULTS A total of 18 786 subjects were recruited to the intervention cohort and 18 876 to the control cohort from 7 cities . After 3.5 years , 174 new stroke cases had occurred in the intervention cohort and 253 in the control cohort . The 3.5-year cumulative incidence of total stroke was significantly lower in the intervention cohort than the control cohort ( 0.93 % versus 1.34 % ; RR=0.69 ; 95 % CI , 0.57 to 0.84 ) . The incidence rates of nonfatal and fatal stroke , as well as ischemic and hemorrhagic stroke , were significantly lower in the intervention cohort than the control cohort . The prevalence of hypertension increased by 4.3 % in the intervention cohort and by 7.8 % in the control cohort . The average systolic and diastolic blood pressures increased more in the control cohort than in the intervention cohort . Among hypertensive individuals in the intervention cohort , awareness of hypertension increased by 6.7 % and the percentage of hypertensives who regularly took antihypertensive medication increased 13.2 % . All of these indices became worse in the control cohort . The prevalence of heart diseases and diabetes increased significantly in the both cohorts ( P<0.01 ) . The prevalence of consumption of alcohol increased slightly , and that of smoking remained constant in both cohorts . CONCLUSIONS A community-based intervention for stroke reduction is feasible and effective in the cities of China . The reduction , due to the intervention , in the incidence of stroke in the intervention cohort was statistically significant after 3.5 years of intervention . The sharp reduction in the incidence of stroke may be due to the interventions having blunted the expected increase in hypertension that accompanies aging as well as to better and earlier treatment of hypertension , particularly borderline hypertension . Applied health education to all the residents of the community may have prevented some normotensive individuals from developing hypertension and improved overall health awareness and knowledge Background This paper describes the study protocol , the recruitment , and base-line data for evaluating the success of r and omisation of the PRO-AGE ( PRevention in Older people – Assessment in GEneralists ' practice s ) project . Methods / Design A group of general practitioners ( GPs ) in London ( U.K. ) , Hamburg ( Germany ) and Solothurn ( Switzerl and ) were trained in risk identification , health promotion , and prevention in older people . Their non-disabled older patients were invited to participate in a r and omised controlled study . Participants allocated to the intervention group were offered the Health Risk Appraisal for Older Persons ( HRA-O ) instrument with a site-specific method for reinforcement ( London : physician reminders in electronic medical record ; Hamburg : one group session or two preventive home visits ; Solothurn : six-monthly preventive home visits over a two-year period ) . Participants allocated to the control group received usual care . At each site , an additional group of GPs did not receive the training , and their eligible patients were invited to participate in a concurrent comparison group . Primary outcomes are self-reported health behaviour and preventative care use at one-year follow-up . In Solothurn , an additional follow-up was conducted at two years . The number of older persons agreeing to participate ( % of eligible persons ) in the r and omised controlled study was 2503 ( 66.0 % ) in London , 2580 ( 53.6 % ) in Hamburg , and 2284 ( 67.5 % ) in Solothurn . Base-line findings confirm that r and omisation of participants was successful , with comparable characteristics between intervention and control groups . The number of persons ( % of eligible ) enrolled in the concurrent comparison group was 636 ( 48.8 % ) in London , 746 ( 35.7 % ) in Hamburg , and 1171 ( 63.0 % ) in Solothurn . Discussion PRO-AGE is the first large-scale r and omised controlled trial of health risk appraisal for older people in Europe . Its results will inform about the effects of implementing HRA-O with different methods of reinforcement Does a prepaid group practice deliver less care than the fee-for-service system when both serve comparable population s with comparable benefits ? To answer this question , we r and omly assigned a group of 1580 persons to receive care free of charge from either a fee-for-service physician of their choice ( 431 persons ) or the Group Health Cooperative of Puget Sound ( 1149 persons ) . In addition , 733 prior enrollees of the Cooperative were studied as a control group . The rate of hospital admissions in both groups at the Cooperative was about 40 per cent less than in the fee-for-service group ( P less than 0.01 ) , although ambulatory-visit rates were similar . The calculated expenditure rate for all services was about 25 per cent less in the two Cooperative groups ( P less than 0.01 for the experimental group , P less than 0.05 for the control group ) . The number of preventive visits was higher in the prepaid groups , but this difference does not explain the reduced hospitalization . The similarity of use between the two prepaid groups suggests that the mix of health risks at the Cooperative was similar to that in the fee-for-service system . The lower rate of use that we observed , along with comparable reductions found in non-controlled studies by others , suggests that the style of medicine at prepaid group practice s is markedly less " hospital-intensive " and , consequently , less expensive The Multiphasic Health Checkup Evaluation Study , a long-term clinical trial , has been completed . A study group of 5156 men and women age 35 - 54 at entry was urged to have annual multiphasic health checkups ( MHCs ) for 16 years . A control group of 5557 comparable subjects was not so urged but was followed up in a comparable fashion . The mean and median number of MHCs per person were 6.8 and 6 , respectively , in the study group and 2.8 and 1 , respectively , in the control group . During 16 years the study group experienced a 30 % reduction ( p less than 0.05 ) in deaths from pre-specified " potentially postponable " causes , largely associated with lower death rates from colorectal cancer and hypertension . This reduction was most pronounced in the early years of the study . The two groups did not differ to a statistically significant degree in mortality from all other causes ( 84 % of total mortality ) or in total mortality . There was no difference in self-reported disability in the overall groups . In the setting of our prepaid health care plan where MHCs were already available on a voluntary basis , a program of urging middle-aged persons to undergo regular MHCs brought about a substantial reduction in mortality from preselected diseases Context Minority and low-income women have low screening rates for cancer . Contribution In this trial from 11 community and migrant health centers in New York City , 1413 women overdue for cancer screening were r and omly assigned to receive a telephone-based intervention ( delivered by 8 prevention care managers ) or usual care . The intervention included information about breast , cervical , and colorectal cancer and motivational and logistical support for obtaining screening . Within 18 months , the screening rates for all 3 forms of cancer increased more with telephone support than through usual care . Implication s Telephone support delivered by trained personnel can improve cancer screening rates among some minority , low-income women . The Editors Higher screening rates for breast , cervical , and colorectal cancer could reduce cancer mortality rates substantially ( 1 - 4 ) . Current cancer screening rates are particularly disappointing among ethnic minorities and individuals with low socioeconomic status ( 5 , 6 ) who often present with late-stage diagnoses ( 7 ) and have high mortality rates ( 8 , 9 ) . Interventions to increase cancer screening have shown limited sustainability and effect on health care disparities . A previous study showed that an office systems approach , which used a medical record flowsheet and practice teamwork , increased screening rates by 20 % to 33 % in small rural community practice s ( 10 ) ; however , a similar intervention was less effective in larger urban practice s ( 11 ) . An office intervention in low-income setting s in Florida increased mammography use and home fecal occult blood testing at 12 months ( 12 ) , but rates decreased substantially after research support ended ( 13 ) . Use of the telephone to support cancer screening is well documented ( 14 - 18 ) , but interventions have typically addressed a single form of cancer screening . In some setting s , telephone infrastructures to support childhood immunization ( 19 ) and patients with chronic illnesses ( 20 - 23 ) already exist . These infrastructures could add screening support for patients who are already enrolled , or they could exp and services to others while making minimal additional dem and s on primary care practice s ( 24 ) . This paper reports the results of a r and omized , controlled trial that tested the effect of central ized telephone care management on cancer screening rates among women 50 to 69 years of age who obtained care at community and migrant health centers in New York City . Methods Setting s Federally qualified community and migrant health centers provide comprehensive community-oriented primary care to over 12 million patients nationally ( 25 ) and are uniquely positioned to deliver cancer screenings to underserved and minority population s. We sought participation from 15 of the 21 community and migrant health centers in New York City because of their anticipated ability to provide sufficient patients for the study and their affiliations with tertiary care facilities that conduct mammography and colorectal screening and provide follow-up services for abnormal test results . Of these 15 sites , 2 were involved in competing research projects , 2 had few patients who were likely to be eligible and therefore served as pilot sites , and the remaining 11 participated . Clinical Directors Network , a practice -based research network in New York City , was responsible for recruiting clinicians , practice s , and women and for implementing the intervention and evaluation . The project was approved by the Committee for the Protection of Human Subjects at Dartmouth College , by the institutional review board at Clinical Directors Network , and by all relevant bodies responsible for review ing research at participating community and migrant health centers . Patients Recruitment Women were approached by research assistants during routine visits to the centers or were referred by a clinician . Research assistants explained the study and obtained written informed consent from women who agreed to participate . Women were compensated $ 15 for participating in an interview whether or not they met eligibility criteria . Eligibility Eligible women were 50 to 69 years of age , were overdue for at least 1 cancer screening according to their medical records , were patients of the center for at least 6 months , and had no plans to move or change health centers within 15 months . We excluded women whose primary language was not English , Spanish , or Haitian Creole and those who were acutely ill or currently receiving cancer treatment . After we obtained consent , a research assistant review ed patient medical records to confirm eligibility . Mammography and Papanicolaou tests that were performed within the past year were seen as evidence of breast and cervical cancer screening , respectively , whereas reports of home fecal occult blood testing within the past year , sigmoidoscopy within the past 5 years , or colonoscopy within the past 10 years were seen as evidence of colorectal cancer screening . Women whose charts indicated that they were up to date on all 3 cancer screenings were excluded . We also excluded women with unresolved abnormal screening results ( for example , positive results on home fecal occult blood testing ; mammography results that were categorized as American College of Radiology level 0 , 4 , or 5 ; and certain Papanicolaou test results ) and notified their physicians of these findings . Design Eligible , consenting women were grouped by center , duration of enrollment at their center ( 12 months or > 12 months ) , and the number of cancer screenings that they had received at recommended intervals ( 0 or 1 screening or 2 screenings ) . The New Yorkbased research assistant assigned women in each group to receive the intervention or usual care by using sealed r and omization forms that were produced by Dartmouth College staff with a computer-based r and om-number generator . Patients were informed of their group assignment individually by telephone . At time of consent , all women received the publication titled Put Prevention into Practice Personal Health Guide ( 26 ) , which contained information regarding recommended preventive services . Women who were assigned to the usual care group received a single telephone call during which trial staff answered questions about preventive care , informed women of their usual care status , advised them to obtain needed preventive care from their primary care clinician , and thanked them for their participation . Women who were assigned to the intervention group received a series of telephone support calls from a trained prevention care manager who was monitored to ensure quality and consistency . In much the same way that patient navigators guide women through the health care system during cancer treatment ( 27 ) , prevention care managers facilitated the screening process for each woman by addressing barriers that prevent or delay receipt of cancer screenings . Prevention care managers received 7 hours of training , including an overview of the U.S. Preventive Services Task Force guidelines ( 28 - 30 ) ; a review of barriers to breast , cervical , and colorectal cancer screenings ; and detailed explanations of the targeted screenings . Additional training included role-playing telephone calls during which the managers used the intervention scripts . Thereafter , logs were review ed in monthly meetings to ensure fidelity to the intervention . The 8 prevention care managers were women , and most were college graduates . Their assignments were determined by patient language needs . Each care manager focused most of her work on patients from 1 or 2 sites while supporting smaller numbers of patients from other sites ; contact with clinicians was limited . During the first call with a patient in the intervention group , the prevention care manager answered questions about the health guide and confirmed or up date d screening date s found in the woman 's medical record . She next determined how ready the woman was to act on each screening ( 31 ) and worked with the woman to prioritize overdue screenings . The prevention care manager then provided motivational support , responding to each participant 's specific barriers to screening by using a structured script that was developed through an earlier series of interviews with women ( 32 ) . Some participants had been advised during office visits with their clinicians to undergo screening ; those who had not received such recommendations were sent a written recommendation from their clinician . Women who reported that they had difficulty communicating with their physician were sent brightly colored patient activation cards that listed overdue screenings , which they could share with their clinician at their next appointment . Care managers also scheduled appointments , provided accurate information about screenings over the telephone and by mail , prompted women with appointment reminder calls and letters , provided directions to screening facilities , and helped women to find a means of transportation to appointments . During subsequent calls , which continued for 18 months or until the patient was up to date for all screenings , the prevention care manager asked about future appointments and screenings the patient had received since the last call . The manager then responded to new and ongoing barriers for remaining overdue screenings . Only clinicians , not care managers , were responsible for ordering screenings at all but 2 centers , which permitted care managers to mail home fecal occult blood test kits directly to women who were willing to perform this test . Evaluation Descriptive data on the centers were gathered from surveys that were completed by clinicians and clinical directors . Outcome data were based on review s of patient medical records , which were conducted at least 3 months after the intervention period to allow for the time lag between receipt of a service and the availability of documentation . Data included patient demographic characteristics , screening date s and results , chronic Preventive case management was implemented by Sharp Healthcare of San Diego with the intention of complementing primary care for geriatric patients enrolled in PacifiCare ’s Secure Horizons Medicare plan . This article presents patient outcomes after 12 months of participation . The program featured an annual screening question naire , appointment monitoring , disease education , and self-management support . It used a prospect i ve design , tracking r and omly assigned treatment ( n= 1,537 ) and control patient sample s ( n = 1,542 ) for 12 months . Outcomes included physical and mental health status ; hospital , ER , and nursing home use ; hospital days and expenditures among persons having an inpatient stay ; and primary care physician visits . Utilization data were obtained from Sharp Healthcare systems and from screening question naires . No statistically significant main effects were found , but persons with three or more independent activity of daily living limitations were about half as likely to have a nursing home admission if they were in case management rather than in the control group BACKGROUND The potential of primary care practice setting s to prevent disease and morbidity through health habit counseling , screening for asymptomatic disease , and immunizations has been incompletely met . This study was design ed to test a practice -tailored approach to increasing preventive service delivery with particular emphasis on health habit counseling . DESIGN Group r and omized clinical trial and multi method process assessment . SETTING / PARTICIPANTS Seventy-seven community family practice s in northeast Ohio . INTERVENTION After a 1-day practice assessment , a nurse facilitator met with practice clinicians and staff and assisted them with choosing and implementing individualized tools and approaches aim ed at increasing preventive service delivery . MAIN OUTCOME MEASURE Summary scores of the health habit counseling , screening and immunization services recommended by the U.S. Preventive Services Task Force up to date for consecutive patients during r and omly selected chart review days . RESULTS A significant increase ( p=0.015 ) in global preventive service delivery rates at the 1-year follow-up was found in the intervention group ( 31 % to 42 % ) compared to the control group ( 35 % to 37 % ) . Rates specifically for health habit counseling ( p=0.007 ) and screening services ( p=0.048 ) were increased , but not for immunizations . CONCLUSIONS An approach to increasing preventive service delivery that is individualized to meet particular practice needs can increase global preventive service delivery rates BACKGROUND Although absolute risk of death associated with raised blood pressure increases with age , the benefits of treatment are greater in older patients . However , fewer patients in this group are identified , treated , and controlled . AIM To evaluate the impact of the provision of different levels of feedback on identification , treatment , and control of older patients with hypertension . DESIGN OF STUDY R and omised controlled trial . SETTING Fifty-two Scottish general practice s. METHOD Practice s were r and omly allocated to either control ( n = 19 ) , audit only feedback ( n = 16 ) , or audit plus risk feedback , prioritising patients by absolute risk ( n = 17 ) . Electronic data were extracted from practice computer systems annually from 1999 to 2001 and used to develop feedback . Data were collected for 30 345 patients aged 65 - 79 years . RESULTS The majority of known patients with hypertension in each group had an initial blood pressure recorded ( control = 89.6 % ; audit = 80.4 % ; risk = 96.1 % ) and this increased over the study period ( control = 92.3 % ; audit = 86.0 % ; risk = 96.6 % ) . Initially , more than 80 % of patients in each group were treated but many were uncontrolled ( blood pressure > /=160/ > /=90 mmHg ) ( control = 41.5 % ; audit = 41.3 % ; risk = 36.1 % ) . The numbers of untreated and uncontrolled patients in each group reduced ( control = 32.3 % ; audit = 38.3 % ; risk = 32.6 % ) . There was some evidence of a significant difference in mean systolic pressure between the audit plus risk and audit only groups : ( 149.6 versus 152.7 mmHg ; P = 0.019 ) and of significantly greater control in the audit plus risk group compared with the other groups 49.4 % ( versus audit only = 35.4 % ; versus control = 46.5 % ; odds ratio = 1.72 [ 95 % confidence interval = 1.09 to 2.70 ] ; P = 0.019 ) . CONCLUSIONS Levels of identification , treatment , and control improved in each group . Although there were still significant numbers of patients with uncontrolled hypertension , there is some evidence to suggest that providing patient-specific feedback may have a positive impact on identification and management of hypertension in older people and produce an increase in control BACKGROUND There have been many reports of the adverse psychological effects of screening . Here we discuss the results of a r and omized controlled study --one of the first to address this issue . AIM To determine the extent to which participation in a population -based intervention programme that aims to reduce the risk of cardiovascular diseases raises concerns about health , or undermines a belief in the ability to reduce that risk . METHOD A r and omized controlled trial involving 13 general practice s in Engl and , Wales and Scotl and was conducted . Two thous and , nine hundred and eighty-four middle-aged men and women undergoing cardiovascular risk-screening and intervention , and a r and omized comparison group of 3,576 men and women from the same practice s , who were not offered the intervention , were compared on three outcomes : perception of current health , perceived risk of suffering a heart attack , and perceived ability to reduce the risk of suffering a heart attack . RESULTS We found no evidence to suggest that participation in this one-year , population -based intervention programme , to reduce the risk of cardiovascular disease raised concerns about health or risk of a heart attack ; indeed , those in the intervention group were slightly more optimistic about their health . Alterations in perceptions of current health and the risk of suffering a heart attack were associated directly with true alterations in risk factors . A more noticeable effect on participants in this intervention programme was a reduction in their perceived ability to further reduce their risks of a heart attack . This was associated with a decrease in weight and with quitting smoking . CONCLUSION Contemporary screening and intervention programmes in primary care , aim ed at reducing risk of cardiovascular disease , do not necessarily lead to raised anxiety or concern about health . A more subtle effect of screening would appear to be one of reassurance in the face of continuing , albeit reduced , risk Objective Community-based cardiovascular disease ( CVD ) risk factor screening programs have been used successfully in rural health improvement initiatives . However , little is known about what consumers like or dislike about them , which is a barrier to the design of future process improvements . The objective of this study was to examine the degree to which health risks and participant characteristics predicted screening satisfaction . Design This study utilized a cross-sectional survey design . Setting Data was collected as part of the broader Heart of New Ulm Project , which is a community-based CVD prevention demonstration project based in rural Minnesota . Participants There were 126 r and omly invited individuals from the CVD risk factor screenings , with 118 individuals who agreed to participate and had complete data available for analyses . Methods A multivariate logistic regression analysis was used to examine the association between demographics , lifestyle , and biometric risk factors and screening satisfaction . Results Twenty percent of respondents indicated some level of dissatisfaction with the screening process . Satisfied participants were more likely to be female ( OR=4.15 ) , not have an optimal lifestyle ( OR=3.47 ) , and have an intention to improve their lifestyle habits ( OR=3.26 ) . Age , education , and CVD risk level were not significant predictors in the final model . Conclusion Satisfaction was high in this screening program , with healthy males being least satisfied with their experience . This has implication s for the design of future intervention efforts , as they may require specific programmatic features and more specialized , targeted marketing strategies to attract a broad spectrum of participants likely to benefit BACKGROUND There is increasing political pressure on the medical profession to approach welfare diseases , such as coronary heart disease and diabetes , through prevention . General practitioners are required to offer regular health checks to healthy people , in spite of the lack of scientific evidence for the universal need , usefulness and side effects of such an intervention . R and omized controlled trials are needed . AIM A study was carried out to investigate people 's interest in participating in health checks and in discussion s about health with their own general practitioner , participants ' health status , the proportion who received health advice following health checks , and the lifestyle goals they set following discussion with their general practitioner . This study reports the baseline data from a five-year r and omized , controlled , prospect i ve , population -based study in general practice s in Ebeltoft , Denmark . METHOD All general practitioners from the four practice s in Ebeltoft and a r and om sample of 2000 people aged between 30 and 50 years were invited to participate . Participants were r and omly divided into three groups -- one control group and two intervention groups . One intervention group were given a health check which included being screened for cardiovascular risk factors , lung and liver function , fitness , sight and hearing and an optional test for the human immunodeficiency virus ( HIV ) ; this group received written feedback from the general practitioner . The other intervention group were also given a health check and written feedback ; in addition , they were given the opportunity to attend their general practitioner to discuss preventive health . RESULTS A total of 1370 people participated in the study ( 69 % response rate ) . Health advice was given to 76 % of 905 participants following health checks . Almost all of the 456 participants ( 96 % ) who were offered the opportunity of discussing their health with their general practitioner took up the offer ; 64 % of the 456 participants reported that they had decided to undertake lifestyle changes . Eleven of those who discussed their health with the doctor were referred to a specialist ( 2 % ) . CONCLUSION There was considerable interest in participating in health promotion . Three out of four of those having a health check were given health advice . Two out of three of those offered a health talk with the general practitioner appeared willing to make relevant lifestyle changes . Long-term follow up is needed to determine effects and side effects of health checks and health talks BACKGROUND Previous interventions targeting primary care practitioners with the aim of increasing preventive care delivery have demonstrated limited effectiveness . The primary aim of this study was to assess the effectiveness of a computerized continuing medical education program to increase rates of three screening behaviors ( cholesterol , blood pressure , and cervical screening ) and to identify three risk behaviors ( smoking , alcohol consumption , benzodiazepine use ) in general practice . METHODS Nineteen general practitioners were r and omly allocated to intervention or control conditions . Those given the intervention received a computerized feedback system . The intervention was delivered using a touch-screen computer located in the surgery waiting area . The preventive behaviors of interest were patient smoking , alcohol use , benzodiazepine use , and blood pressure , cholesterol and cervical screening using the Papanicolou test . Differences in performance by group in each of the outcomes was measured at baseline and 3-month follow-up . Logistic regression analyses with generalized estimating equations were conducted as the main analyses . RESULT At 3-month follow-up , statistically significant differences were evident in the following outcome measures : accurate classification of benzodiazepine users ( z = 2.8540 , P < 0.05 ) ; accurate classification of non-benzodiazepine users ( z = 2.7339 , P < 0.05 ) ; accurate classification of hazardous or harmful alcohol drinkers ( z = 2.3079 , P < 0.02 ) ; blood pressure screening ( z = 3.4136 , P < 0.001 ) ; and cholesterol screening ( z = 6.6313 , P < 0.001 ) . CONCLUSION A computerized system of performance-specific feedback was effective at increasing some preventive care services in general practice Aims /hypothesisThere is limited evidence on how multifactorial treatment improves outcomes of diabetes when initiated in the lead time between detection by screening and diagnosis in routine clinical practice . Cardiac autonomic neuropathy ( CAN ) in people with diabetes indicates widespread damage to the autonomic nervous system , which may severely affect health and quality of life . We examined effects of early detection and subsequent intensive treatment of type 2 diabetes in primary care on the prevalence of CAN at the 6-year follow-up examination in a pragmatic cluster-r and omised parallel group trial . Methods One hundred and ninety general practice s were r and omised to deliver either intensive multifactorial treatment ( IT ) or routine care ( RC ) as recommended by national guidelines to patients with type 2 diabetes , identified through a stepwise screening programme in the primary care setting . 1533 people ( IT , n = 910 ; RC , n = 623 ) were identified and included . At the 6-year follow-up examination , measures of CAN were applied in an unselected sub sample of 777 participants using heart rate variability analysis and st and ard tests of CAN . Results At the 6-year follow-up examination , the prevalence of early CAN was 15.1 % in the RC group and 15.5 % in the IT group , while manifest CAN was present in 7.1 % and 7.3 % , respectively . We found no statistically significant effect of intensive treatment on the prevalence of CAN compared with routine care . Conclusions /interpretationIn the Danish arm of the ADDITION Study , signs of CAN were highly prevalent 6 years after a screening-based diagnosis of type 2 diabetes . Intensive multifactorial treatment did not significantly affect the prevalence of CAN compared with routine care . However , at follow-up the level of medication was also high in the RC group BACKGROUND Cardiovascular disease ( CVD ) is the leading cause of global mortality . Risk factor management in clinical practice often relies on relative risk modification rather than the more appropriate absolute risk assessment . AIM To determine whether patients receiving more-frequently design ated GP visits had increased benefit in terms of their absolute CVD risk assessment , as compared with patients in receipt of their usual GP care . DESIGN AND SETTING Prospect i ve , open , pragmatic block r and omised study in a 1:1 group allocation ratio in three Western Australian general practice s. METHOD A convenience sample ( n = 1200 ) of patients aged 40 - 80 years were r and omised to 3-monthly GP visits ( five in total for the intensive ) or usual GP care ( two in total for the opportunistic ) , with 12 months ' follow-up . The main outcome was absolute CVD risk scores based on the New Zeal and Cardiovascular Risk Calculator . Others outcome measures were weight , height , waist circumference , blood pressure , and fasting blood lipids and glucose . RESULTS There were 600 patients per group at baseline . At 12 months ' analysis there were 543 in the intensive group and 569 in the opportunistic group . Mean ( st and ard deviation [ SD ] ) absolute CVD risk reduced significantly between baseline and 12 months in the intensive group ( 6.28 % [ 5.11 ] to 6.10 % [ 4.94 ] ) but not in the opportunistic group ( 6.27 % [ 5.10 ] to 6.24 % [ 5.38 ] ) . There was a significant reduction between baseline and 12 months in mean ( SD ) total cholesterol ( 5.28 mmol/l [ 0.94 ] to 5.08 mmol/l [ 0.96 ] ) ; low-density lipoprotein cholesterol ( 3.08 mmol/l [ 0.87 ] to 2.95 mmol/l [ 0.89 ] ) ; triglyceride ( 1.45 mmol/l [ 0.86 ] to 1.36 mmol/l [ 0.84 ] ) ; and in mean ( SD ) waist circumference in men ( 98.74 cm [ 10.70 ] to 97.13 cm [ 10.20 ] ) and females ( 90.64 cm [ 14.62 ] to 88.96 cm [ 14.00 ] ) in the intensive group . CONCLUSION A targeted approach using absolute risk calculators can be used in primary care to modify global CVD risk assessment The objective of this study was to estimate the health service use and costs result ing from the introduction of the interRAI Minimum Data Set-Home Care ( MDS-HC ) assessment compared with usual assessment .A r and omised controlled trial of elderly people in New Zeal and measured the use and cost of prescribed and delivered ( 4 months post- assessment ) health services of 153 participants assessed using the st and ard [ Needs Assessment and Service Co-ordination ( NASC ) ] tool , and 158 participants assessed using the MDS-HC . The results suggest that the MDS-HC result ed in more prescribed personal health and community services , and less disability support services than with NASC . The cost of prescribed services was significantly greater for the MDS-HC ( NZ$1840 ) than the NASC ( NZ$1522 , P < 0.001 ) . The cost of delivered services was significantly greater for the MDS-HC (NZ$4809)than the NASC ( NZ$2727 , P < 0.001 ) , including higher costs of hospitalizations ( NZ$2523 vs. NZ$1112 , P= 0.257 ) . There were pronounced differences among ' low-need ' compared with ' high-need'elderly people . These results suggest that the interRai assessment tool result ed in greater cost of prescribed preventive services and less prescribed disability services than the NASC . However , differences in delivered services were driven primarily by differences in hospitalizations . The results highlight the importance of integrating the assessment procedure with the delivery of health services , but suggest that further study is warranted . The results have implication s for purchasers of health services for elderly people Aims : The intention was to investigate whether preventive health checks and health discussion s are cost effective . Methods : In a r and omized trial the authors compared two intervention groups ( A and B ) and one control group . In 1991 2,000 30- to 49-year-old persons were invited and those who accepted were r and omized . Both intervention groups were offered a broad ( multiphasic ) screening including cardiovascular risk and a personal letter including screening results and advice on healthy living . Individuals in group A could contact their family physician for a normal consultation whereas group B were given fixed appointments for health consultations . The follow-up period was six years . Analysis was carried out on the ` ` intention to treat ' ' principle . Outcome parameters were life years gained , and direct and total health costs ( including productivity costs ) , discounted by 3 % annually . Costs were based on register data . Univariate sensitivity analysis was carried out . Results : Both intervention groups have significantly better life expectancy than the control group ( no intervention ) . Group B and ( A ) significantly gain 0.14 ( 0.08 ) life years more than the control group . There were no differences in average direct ( 3,255 ( 3,703 ) versus 4,186 ) and total costs ( 10,409 ( 9,399 ) versus 10,667 ) . The effect in group B is , however , better than in group A with no significant differences in costs . The results are insensitive to a range of assumptions regarding costs , effects , and discount rates . Conclusions : Preventive health screening and consultation in primary care in 30- to 49-year-olds produce significantly better life expectancy without extra direct and total costs over a six-year follow-up period CONTEXT Cardiovascular disease is common and preventable . Primary care is the preferred setting for individual prevention and management . OBJECTIVE This study analyzed the long-term outcome of cardiovascular risk in a family practice population . DESIGN A longitudinal cohort analysis of cardiovascular outcome after 18 years , in participants of a r and omized controlled trial ( RCT ) of cardiovascular prevention . In 1977 , a RCT with cluster r and omization at practice level assessed the effects of a 1-year preventive intervention in patients 20 to 50 years of age . Cardiovascular risk factors ( smoking , body mass index , blood pressure , serum cholesterol , family history , and physical activity ) were measured and intervention was a practice -nurse support for the follow-up of those at elevated risk . The control practice s prescribed care as usual . Between 1994 and 1995 , all participants were approached again , to analyze subsequent ( cardiovascular ) mortality and morbidity and their cardiovascular risk in a r and om sample . SETTING The Nijmegen Academic Family Practice s Network , The Netherl and s. PARTICIPANTS All participants ( 7092 ) of the 1977 screening for follow-up morbidity and mortality , 2600 for re-measurement risk factors . OUTCOME MEASURES Cardiovascular risk factors ; cardiovascular morbidity and mortality 1977 - 1995 . RESULTS Follow-up was achieved in 5945 participants ( 84 % ) and 2335 participated in the re-measurement ( 89 % ) . No effects of the preventive intervention were found , but those initially at low risk profile were still so 18 years later . Risk of subsequent cardiovascular mortality and morbidity was related to baseline risk , but for women , the absolute risk was low in all risk strata and lower than predicted from international references . CONCLUSIONS This study demonstrated the feasibility of family practice network research in pursuing longitudinal research . A single cardiovascular screening result ed in reliable risk assessment : those initially at low risk still were so after 18 years . Effects of a 1-year intensive intervention could no longer be demonstrated A r and omized trial was conducted in five general practice s in and around Aylesbury , Buckinghamshire to assess the motivational effect of cholesterol measurement on compliance with advice to reduce dietary fat intake and to stop smoking . The advice was given by practice nurses during health checks for cardiovascular risk factors . A total of 578 patients were recruited to the study and r and omized into two groups . Both groups were given the same advice and were followed up after a median of three months , but the intervention group was also given immediate feedback on their cholesterol concentration . Follow up was completed for 88.2 % of subjects , and those who were not followed up were assumed not to have changed their behaviour . The mean fall in total cholesterol at follow up was 0.11 mmol l-1 ( 95 % confidence interval 0.03 to 0.18 ) in the intervention group who were told their cholesterol result and 0.02 mmol l-1 ( 95 % CI -0.06 to 0.10 ) in the control group who were not . The proportion of smokers who were not smoking at follow up was 10.7 % and 10.1 % in the two groups , respectively . Patients in the intervention group with an initial total cholesterol level of 6.50 mmol l-1 or greater showed a mean fall of 6.2 % in cholesterol level whereas those with an initial cholesterol level of less than 5.20 mmol l-1 experienced a mean increase of 3.6 % , but as differences of this magnitude were also seen in the control group they probably reflect regression to the mean rather than an effect of knowledge of cholesterol level . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To investigate the long-term effects of multifactorial primary prevention of cardiovascular diseases ( CVD ) . DESIGN The 5-year r and omized , controlled trial was performed between 1974 and 1980 . The subjects and their risk factors were reevaluated in 1985 . Posttrial mortality follow-up was continued up to December 31 , 1989 . SETTING Institute of Occupational Health , Helsinki , Finl and , and Second Department of Medicine , University of Helsinki . PARTICIPANTS In all , 3490 business executives born during 1919 through 1934 participated in health checkups in the late 1960s . In 1974 , 1222 of these men who were clinical ly healthy , but with CVD risk factors , were entered into the primary prevention trial ; 612 were r and omized to an intervention and 610 to a control group . INTERVENTIONS During the 5-year trial , the subjects of the intervention group visited the investigators every fourth month . They were treated with intensive dietetic-hygienic measures and frequently with hypolipidemic ( mainly clofibrate and /or probucol ) and antihypertensive ( mainly beta-blockers and /or diuretics ) drugs . The control group was not treated by the investigators . MAIN OUTCOME MEASURES Total mortality , cardiac mortality , mortality due to other causes . RESULTS Total coronary heart disease risk was reduced by 46 % in the intervention group as compared with the control group at end-trial . During 5 posttrial years , the risk factor and medication differences were largely leveled off between the groups . Between 1974 and 1989 the total number of deaths was 67 in the intervention group and 46 in the control group ( relative risk [ RR ] , 1.45 ; 95 % confidence interval [ CI ] , 1.01 to 2.08 ; P = .048 ) ; there were 34 and 14 cardiac deaths ( RR , 2.42 ; 95 % CI , 1.31 to 4.46 ; P = .001 ) , two and four deaths due to other CVD ( not significant ) , 13 and 21 deaths due to cancer ( RR , 0.62 ; 95 % CI , 0.31 to 1.22 ; P = .15 ) , and 13 and one deaths due to violence ( RR , 13.0 ; 95 % CI , 1.70 to 98.7 ; P = .002 ) , respectively . Multiple logistic regression analysis of treatments in the intervention group did not explain the 15-year excess cardiac mortality . CONCLUSION These unexpected results may not question multifactorial prevention as such but do support the need for research on the selection and interaction(s ) of methods used in the primary prevention of cardiovascular diseases BACKGROUND The long-term effect of most interventions has not been studied . Changes due to interventions to improve patient care may revert to baseline after the intervention stimulus ends . This analysis reports the 24-month follow-up of a practice -tailored intervention to increase preventive service delivery rates . DESIGN Group r and omized clinical trial with 24-month follow-up of intervention sites . SETTING / PARTICIPANTS Seventy-seven community family practice s in northeast Ohio . INTERVENTION Practice -individualized facilitation of implementation of tools and approaches . MAIN OUTCOME MEASURES Summary scores of health habit counseling , screening , and immunization services recommended by the U.S. Preventive Services Task Force that were up to date for consecutive patients during r and omly selected chart review days . RESULTS Previously reported increases in global preventive service delivery rates , health habit counseling , and screening rates at 12 months were sustained after 24 months . CONCLUSIONS A practice -individualized approach can result in sustainable increases in rates of preventive service delivery , even 1 year after the outside intervention stimulus ends . Tailoring of approaches to the unique characteristics of each practice may result in institutionalization of changes INTRODUCTION Cardiovascular disease ( CVD ) risk screening may rely partly on self-report information . The accuracy of self-reporting in relation to the actual risk factor status is insufficiently known . DESIGN Self-report ( yes , no , do n't know ) of presence of hypertension , hyperlipidemia , and overweight was compared to the corresponding risk factor data obtained by physical examination and blood analysis . The examinations carried out in a primary health care setting in Sweden were on a r and omized population of 122 men and 127 women aged 20 to 60 years . RESULTS Unawareness of hyperlipidemia was 71 % in women and 56 % in men , as compared to 29 % or lower for the other risk factors . The sensitivity of self-report was 69 % or higher for the other risk factors , with the exception of hypertension in women , where it was 29 % . Specificity was generally high , except for hyperlipidemia . CONCLUSION On a population level , self-reports of hypertension , hyperlipidemia , and overweight provide a feasible selection instrument by which a sub population with high risk factor frequency can be identified . However , the rate of misclassification is considerable . For hyperlipidemia , the benefit of self-reporting is presently limited , due to the high unawareness of this risk factor . Individual awareness and accurate knowledge about the presence or absence of risk factors needs to improve before self-reporting can be used as a reliable instrument in risk factor screening OBJECTIVE The aim of the study was to examine the effect of a computer-generated patient-held medical record summary ( CHR ) and /or a written personal health record ( PHR ) on patients ' attitudes , knowledge and behaviour concerning health promotion . METHOD It was conducted in five general practice s in Oxfordshire . Patients aged 25 - 65 years in each practice were r and omly assigned to receive either a CHR plus PHR , CHR only , PHR only , or no personal record . Patients were recruited by mail ( one practice ) or opportunistically by nurses ( four practice s ) . Health checks were carried out using the r and omly assigned record , which the patient retained . Attitudes to patient-held records , and pre- and post-intervention knowledge and behaviour concerning health promotion , were assessed using question naires . Only those who responded to ' before ' and ' after ' question naires were included in the analysis . RESULTS A sample of 261 patients was obtained from mail recruitment and 103 from opportunistic nurse recruitment . Patients receiving a CHR as part of mail recruitment were significantly more likely to attend for a health check ( P = 0.016 ) . Those receiving both PHR and CHR were more likely to keep ( P = 0.014 ) and use ( P = 0.029 ) the record . Those receiving PHR as part of the package improved their knowledge of health promotion and became more aware of and more likely to change their life-style ( P = 0.022 ) . CONCLUSIONS The effectiveness of a computer-generated patient-held health summary and an explanatory booklet together is greater than either separately in changing patients ' knowledge attitudes and behaviour concerning health promotion Background Various strategies have been used to induce lifestyle changes to reduce ischaemic heart disease ( IHD ) with various successes . The aim of Inter99 is to assess the effect on IHD incidence of individually tailored non-pharmacological intervention on lifestyle using a newly developed computer-based health educational tool . The article describes the study and baseline results . Methods From a population of 61,301 individuals two r and om sample s ( high intensity intervention group ( A ) , n = 11,708 ; low intensity intervention group ( B ) , n = 1308 ) are screened to assess their absolute risk of IHD . Those at high risk receive individual lifestyle counselling . Individuals in group A are furthermore offered lifestyle counselling in groups on smoking cessation or physical activity/diet over a 6-month period . Individuals in group B are referred to their GP . High-risk persons are re-counselled after 1 and 3 years and the whole group is re-invited after 5 years . The remaining 48,285 ( group C ) are followed by question naire . The total population is followed through central registers . Intermediate end-points are changes in lifestyle , cholesterol , blood pressure and body mass index . Final end-point is reduction in incidence of IHD . Results The r and omization leads to comparable groups . Participation rate was 52.5 % . A total of 60 % fulfilled the predetermined criteria for being at high risk for developing IHD . After an individual lifestyle counselling 41 % accepted group-based counselling . Conclusion This large r and omized population based trial discloses a noticeable need for and acceptance of lifestyle intervention in the general population . Eur J Cardiovasc Prevention Rehab 10:377 - 386 © 2003 Lippincott Williams & Wilkins Summary During the last 20 years several r and omised controlled trials have been published about preventive home visits to old people , but the benefit of the visits is still controversial and under debate . Based on a state law from the Ministry of Social Affairs in 1998 , the municipalities in Denmark are obliged to offer home visits twice a year to all citizens 75 years and older . After six years with this law , there is still variation of how the law is managed and implemented . About 60 % of the elderly people accept and receive the visits . Less than 50 % of the municipalities have made specific guidelines and quality assurance indicators . More than the half have systematic ally used the visits to collect information of community needs and older people ’ wishes to be used for administrative and political purpose s . In a prospect i ve , controlled , feasibility study conducted over a 3-year period we found that a brief , manageable and ongoing educational intervention towards professionals working with preventive home visits is feasible and improves older people ’s functional mobility . ZusammenfassungIn den letzten 20 Jahren sind verschiedene r and omisierte kontrollierte Studien über Hausbesuche bei alten Menschen veröffentlicht worden , aber der Nutzen dieser Besuche wird noch immer kontrovers diskutiert . Aufgrund eines Gesetzes aus dem Sozialministerium von 1998 sind alle Gemeinden in Dänemark verpflichtet , jedem Bürger ab 75 Jahren 2-mal jährlich Hausbesuche anzubieten . Nachdem das Gesetz 6 Jahre in Kraft ist , wird es in der Durchführung immer noch uneinheitlich geh and habt . Etwa 60 % der älteren Menschen akzeptieren und empfangen Besuche . Weniger als die Hälfte der Gemeinden haben spezielle Leitlinien oder Qualitätskontrollmechanismen erarbeitet . Mehr als die Hälfte haben bei den Besuchen systematisch Informationen erhoben über die Bedürfnisse und die Wünsche der älteren Menschen , um sie für die Verwaltung und die Politik zu nutzen . In einer prospektiven , kontrollierten Machbarkeitsstudie über den Zeitraum von 3 Jahren , haben wir herausgefunden , dass kurze , praktikable und wiederholte Fortbildungseinheiten für diejenigen , die beruflich mit der Durchführung der präventiven Hausbesuche betraut sind , machbar sind und die funktionale Mobilität älterer Menschen verbessern BACKGROUND Controversy exists regarding the optimal way to provide health promotion education to the elderly . This prospect i ve r and omized study evaluated the effectiveness of individualized assessment and counseling coupled with the receipt of a written health plan on client adherence to health behavior recommendations . METHODS Two hundred thirty-seven ethnically diverse and predominantly low-income adults 60 and older , participating for the first time in an established statewide public health prevention program delivered in both rural and urban clinics , were recruited and r and omly assigned to treatment and control groups . All participants received a st and ardized assessment that included a health history , nutrition assessment , and limited physical exam from a public health nurse . The treatment group additionally received a written personal health plan and individualized counseling to support implementation of the plan . Both groups were interviewed after one year to determine their adherence to the original recommendations . RESULTS Seventeen preventive services and health behaviors were evaluated . There were no statistically significant differences between the groups on health care use and previous health behaviors at baseline . Using logistic regression and controlling for socioeconomic and demographic variables , we found that the treatment group that received a personal health plan and counseling completed significantly more preventive referrals and health behavior changes ( P < .001 ) . CONCLUSIONS A client-centered planning process with supportive counseling by public health nurses , combined with health plans provided to clients , can significantly increase the prevention measures taken by older adults BACKGROUND Regular preventive health screenings are a feature of primary health care in several countries . Studies of the effect of regular preventive health checks have reported different results regarding primary health care utilization . OBJECTIVE To analyse the effect of preventive health screening and health discussion s on contacts to general practice . METHODS A r and omized controlled trial with all GPs in the district of Ebeltoft , Denmark . All middle-aged residents registered with a GP in the district of Ebeltoft were included ( n = 3464 ) . A r and om sample of 2030 subjects was selected for invitation to participate in health screening or health screening and discussion s. The remaining 1434 subjects were never contacted and served as an external control group . Main outcome measure was number of daytime consultations in general practice . RESULTS The annual rate ratios for daytime consultations showed a very clear time trend ( P < 0.0001 ) with a high rate of contacts among invited compared with non-invited subjects during the first year ( P = 0.001 ) followed by a gradual decrease to a lower level after eight years ( P = 0.037 ) . The total rate ratio for daytime consultations was 1.01 ( 95 % CI 0.93 to 1.10 ) . CONCLUSION We observed no differences between the invited group and the non-invited group in any type of contact to general practice when the entire follow-up period was considered . There was a significant trend in rate ratios for daytime consultations with an initial rise followed by a gradual decrease in rate ratios . More investigations are needed to confirm and explore reasons for this trend Background : The burden of chronic obstructive pulmonary disease ( COPD ) is high . Health benefits can be gained in primary care by early detection and preventive measures . Aims : To compare the effectiveness of two strategies for population -based early detection of COPD , taking into account different socioeconomic status ( SES ) setting s. Methods : Practice s were r and omised on strategy and stratified on SES setting . The Respiratory Health Screening Question naire ( RHSQ ) was distributed to all participants . In the practice -managed condition , the practice was responsible for the whole procedure , while in the patient-managed condition , patients were responsible for calculating their RHSQ risk score and applying for a spirometry test . The main outcome measure was the rate of COPD diagnoses after screening . Results : More new COPD patients were detected in the practice -managed condition ( 36 % ) than in the patient-managed condition ( 18 % ) . In low SES practice s , more high-risk patients were found ( 16 % ) than in moderate-to-high SES practice s ( 9 % ) . Recalculated for a st and ard Dutch practice ( 2,350 patients ) , the yield would be 8.9 new COPD diagnoses , which is a 20 % increase of known cases . Conclusions : The practice -managed variant of this screening procedure shows a substantial yield of new COPD diagnoses for both low and moderate-to-high SES practice All male inhabitants of the city of Göteborg , who were born between 1915 - 1922 and 1924 - 1925 were included in the trial , and were 47 to 55 years of age on entry to the study in 1970 to 1973 . One-third of these men were r and omly allocated to an intervention group , whilst the other two-thirds acted as controls . Men of all social classes , employed as well as unemployed , health conscious as well as careless , were invited , with 75 % of these responding to the invitation . The intervention group contained 10,000 men and the control group 20,000 men . The intervention group were given advice on diet , both individually and in groups , the type of advice depending upon serum cholesterol level . Smokers were advised to stop smoking , and men with elevated blood pressure were treated with antihypertensive drugs . Due to the large size of the groups and because they formed a r and om population sample , it was assumed that they had similar characteristics at the start of the trial . Risk factors were only measured in the intervention group at this time , followed by intervention . This design feature solved several ethical problems with regard to no treatment in the control group . These men were , however , subjected to health examinations and treatment as well as general health advice . Risk factor levels were measured in the intervention group , and also in r and om sub sample s ( 11 % ) of the control group after 4 and 10 years . Serum cholesterol , blood pressure and smoking decreased among men in both groups , and only slightly more in the intervention group . ( ABSTRACT TRUNCATED AT 250 WORDS We design ed a r and omized clinical trial to examine effectiveness of a follow-up educational mailing to improve referral completion following a workplace cholesterol screening program . Of 836 employees who participated in a cholesterol screening program at Blue Cross and Blue Shield of Maryl and , 313 ( 37 % ) had a total cholesterol greater than or equal to 200 mg/dL and were referred to their physician for remeasurement and evaluation . Individuals with elevated cholesterol who agreed to a telephone interview two months after screening ( n = 272 ) were r and omized to a control or intervention group . The intervention consisted of a booster mailing two weeks after screening design ed to encourage further physician follow-up and to increase knowledge about cholesterol and its dietary control and about risk factors for coronary heart disease ( CHD ) . No statistically significant differences appeared between the control and intervention groups in rate of referral completion . However , a blood cholesterol level of greater than or equal to 240 mg/dL at the time of screening was the most significant predictor of referral completion ( P less than .0001 ) . Of those r and omized , the association between the number of other additional risk factors for CHD and referral completion was not statistically significant . There was , however , a trend toward reported changes in lifestyle behavior as a result of screening , particularly in diet modification To examine the impact of cholesterol screening with brief nonphysician counseling on cardiovascular risk factors , 886 employees at a large financial services firm underwent fingerstick screening followed by brief ( 3- to 5-minute ) counseling by a registered nurse . At the 6-month follow-up , there were significant declines in total cholesterol levels ( 5.9 to 5.5 mmol/L [ 228 to 213 mg/dL ] ) , weight ( 78 to 75 kg ) , blood pressure ( 119/78 to 115/75 mm Hg ) , and number of people reporting smoking ( 16.8 % to 14.5 % ) among participants with a baseline cholesterol value of 5.2 mmol/L ( 200 mg/dL ) or greater . A r and omized experiment was conducted on 137 participants initially classified as having a " borderline-high blood cholesterol " level ( 5.2 to 6.2 mmol/L [ 200 to 239 mg/dL ] ) to test the impact of frequency of follow-up . Those receiving frequent follow-up ( cholesterol measurement and brief counseling at 2 , 4 , and 6 months ) reported significantly greater dietary change and demonstrated a trend toward greater declines in total cholesterol compared with those receiving follow-up at 6 months only . The results of this study support the feasibility and efficacy of cholesterol screening utilizing brief nonphysician counseling on multiple cardiovascular risk factors and suggest an enhanced effect when patients receive more frequent follow-up Health promotion and disease prevention for the elderly offer the potential for improving the quality of life for the growing population of older adults , while reducing the economic burden on the health system . Whether this potential can be realized depends , in part , on whether those older adults whose health behaviors put them at risk actually use preventive services when offered the opportunity . In 1988 the Health Care Financing Administration began a series of health promotion demonstrations to address health issues related to older adults . This article reports on program participation at one of the five demonstration sites . Over 1,900 community-dwelling Medicare beneficiaries who receive their health care through fee-for-service providers were enrolled in the demonstration . These enrollees were r and omly assigned to control and experimental groups , with the latter offered health screening and promotion services . Nine hundred-seventy-three of the experimental subjects and 938 of the control subjects completed a lengthy telephone interview , which determined each person 's use of preventive services and practice s. Although all 973 experimental subjects were invited by letter and follow-up telephone calls to attend these free-of-charge , Medicare-provided sessions , not everyone attended . We analyzed 17 health behaviors of those who attended the first session and those who did not . Those engaging in these preventive behaviors were neither more nor less likely to attend the screening services . Thus , we found neither " favorable " nor " unfavorable " selection bias in the use of these preventive services OBJECTIVE --To test the benefits of regular surveillance of the elderly at home using an activities of daily living question naire administered by volunteers . DESIGN --R and omised controlled study . PATIENTS --539 Subjects aged 75 and over from two general practice s. INTERVENTION -- All subjects were visited at the beginning and end of the study by volunteers , who completed a scored activity of daily living question naire . The study group were revisited at regular intervals . Individuals with an increase in score greater than 5 were referred to their general practitioners . All interactions with social services and health authorities were recorded for both groups . MAIN OUTCOME MEASURES --Mortality , activity of daily living score , total number of days in institutions , geriatric and psychogeriatric service contacts , primary health care team contacts , use of community support services . RESULTS --The study group were admitted to hospital more often than the controls ( 335 occasions v 252 ) , but the control group spent 33 % more days in institutions , mainly in long term admissions to residential accommodation . The number of falls reported in the control group doubled ( from 17 before the first interview to 36 before the last ) and in the study group remained unchanged ( 12 before both interviews ) . The study group received community support services sooner than the control group . There was no difference between the groups in mortality or activity of daily living score . CONCLUSION --Regular visiting of old people at home by non-professional volunteers using a simple activity of daily living question naire is a practical way of identifying problems and initiating action for this group OBJECTIVES To describe tobacco use , obesity and overweight , high blood pressure , high blood cholesterol and impaired glucose tolerance in Alaska Native and American Indian women living in the Anchorage area . STUDY DESIGN Cross-sectional evaluation of women enrolled in the Traditions of the Heart program . METHODS Traditions of the Heart was a r and omized controlled trial of an intervention to reduce risk factors for cardiovascular disease . Starting in October 2000 , South central Foundation provided a 12-week group lifestyle intervention to eligible Alaska Native and American Indian women aged 40 to 64 residing in the Anchorage area . The study included assessment of biochemical and behavioral risk factors for cardiovascular disease . RESULTS Of the 1334 women who enrolled between October 2000 and July 2005 , 33.5 % were current smokers , 78.8 % were overweight or obese , 10.9 % were hypertensive , 21.4 % had elevated total cholesterol , and 5.6 % had fasting glucose concentrations > or = 126 mg/dL. CONCLUSIONS The women in this study had many risk factors for cardiovascular disease . Interventions are needed to reduce these risk factors among Alaska Native women BACKGROUND The original collaborative project was described in a 1995 Journal article titled " Competing HMOs Collaborate to Improve Preventive Services . " IMPROVE ( IMproving PRevention through Organization , Vision , and Empowerment ) was a large r and omized controlled trial using continuous quality improvement to implement clinical systems to improve the delivery of adult preventive services in primary care setting s. The project was funded by the Agency for Health Care Policy and Research and initiated as a collaboration between two health maintenance organizations ( HMOs ) in the Twin Cities : Health Partners and Blue Plus . METHODOLOGY Forty-four clinics were recruited for the study . Initially the 22 intervention clinics received the multifaceted intervention of leadership support , training on CQI and prevention systems , and consultation and networking opportunities . Next , the comparison clinics received similar assistance , and other clinics were invited into the collaboration . Ultimately , 57 clinics were involved in the project . Multiple collaborations -- among clinics , leaders , and HMOs -- developed during the project . STATUS Despite turmoil in the environment during the project , many benefits have been described , including enhanced leadership , growth of systems thinking , better change management skills , and collaboration of competing organizations . SUMMARY The IMPROVE collaboration survived and flourished in a very competitive market . It was viewed positively by clinicians , medical clinics , and HMOs , and its benefits have extended into the community AIM The aim of this study was to investigate the clinical relevance and consequences of screening for microalbuminuria ( MA ) in a r and omly selected , apparently healthy population sample . MATERIAL AND METHODS A total of 2,113 individuals ( > or = 20 years ) without known diabetes and treated hypertension , all identified in the large population -based Nord-Trøndelag Health Study ( HUNT ) 1995 - 1997 , ( n = 65,258 ) , delivered 3 morning urine sample s for MA analysis . Those with MA , defined as at least 2 out of 3 urine sample s with albumin-to-creatinine ratio ( ACR ) > or = 2.5 mg/mmol , were invited to a second clinical examination . RESULTS In total , 54 men and 54 women had MA , and 42 men ( 84 % ) and 42 women ( 78 % ) attended the second examination . All with MA had 1 or more cardiovascular risk factors , like elevated cholesterol , c-peptides and blood pressure , and they were older than those without MA . Ten men ( 25 % ) and 19 women ( 46 % ) , who were defined as MA-positive at the screening , had normal albumin excretion in the overnight collected urine sample in the second clinical examination . Five men ( 12 % ) and 2 women ( 5 % ) were still followed-up at the hospital out-patient clinic 3 years later . CONCLUSIONS Several individuals in the second examination had cardiovascular risk factors and other pathology , but the clinical benefit of discovering this was not obvious . Due to low positive predictive value and reduced reliability and validity , MA did not satisfy the criteria for a good screening test in this apparently healthy population Background and aims : We describe the enrollment and intervention phases of FRASI ( FRAilty , Screening and Intervention ) , a r and omized controlled trial aim ed at preventing ADL disability in frail older persons screened in primary care . Methods : Patients , 70–85 years old , non-disabled and non-cognitively impaired , were screened for frailty ( score ≤9 on the Short Physical Performance Battery , SPPB ) during primary care visits . Of 447 eligible persons , 410 came to the study clinic and 251 were r and omized into treatment ( n=126 ) and control groups ( n=125 ) . The active group received an intensive medical intervention , and sixteen 90-minute supervised exercise sessions over 8 weeks . The primary outcome was time to ADL disability onset or death in the 12-month period after study enrollment . Results : The two study arms were similar for demographics , cognitive function , physical function and health status . Compared with a population -based sample selected according to FRASI inclusion criteria except SPPB score , FRASI participants had significantly worse health and functional status . Restricting the comparison to persons with SPPB ≤9 , all differences disappeared . The 99 participants ( 78.6 % of 126 ) who completed the intervention participated in a mean of 15.3±1.6 exercise sessions . Conclusions : Screening in primary care for non-disabled , older persons with SPPB ≤9 yields individuals with substantial morbidity , impairments and functional limitations that can be successfully involved in an intensive medical and exercise intervention . Whether such an intervention effectively prevents new disability remains to be confirmed Abstract Objective : To measure the costs and cost effectiveness of the Oxcheck cardiovascular risk factor screening and intervention programme . Design : Cost effectiveness analysis of a r and omised controlled trial using clinical and economc data taken from the trial . Setting : Five general practice s in Luton and Dunstable , Engl and . Subjects : 2205 patients who attended a health check in 1989 - 90 and were scheduled for re-examination in 1992 - 3 ( intervention group ) ; 1916 patients who attended their initial health check in 1992 - 3 ( control group ) . Participants were men and women aged 35 - 64years . Intervention : Health check conducted by nurse , with health education and follow up according to degree of risk . Main outcome measures : Cost of health check programme ; cost per 1 % reduction in coronary risk . Results : Health check and follow up cost £ 29.27 per patient . Estimated programme cost per 1 % reduction in coronary risk per participant was between £ 1.46 and £ 2.25 ; it was nearly twice as much for men as women . Conclusions : The cost to the practice of implementing Oxcheck-style health checks in an average sized practice of 7500 patients would be £ 47 000 , a proportion of which could be paid for through staff pay reimbursements and B and Three health promotion target payments . This study highlights the considerable difficulties faced when calculating the costs and benefits of a health promotion programme . Economic evaluations should be integrated into the protocol s of r and omised controlled trials to enable judgments to be made on the relative cost effectiveness of different prevention strategies . Key messages Research was undertaken to estimate the cost of the health checks and relate the cost to changes in the relative risk of cardiovascular disease The immediate cost of implementing Oxcheck-style health checks in an average sized practice of 7500 patients would be £ 47 000 , which is comparable with the immediate cost of a cervical screening programme The actual costs to the practice would be substantially reduced by staff pay reimbursements and health promotion target payments Further research is required to estimate the wider costs of health checks result ing from the additional use of health care The effects on quality of life and psychological well-being of a health examination programme in a branch of Swedish industry were studied by means of question naires in 124 white-collar workers . They were asked to answer two question naires , one before and the other one month after the examination ( the Nottingham Health Profile ( NHP ) and the Psychological General Well-being Schedule ( PGWB ) ) . Both are well-known and well-documented st and ard question naires used for estimating quality of life and degree of subjective well-being . The answers were compared with those of a control group comprising other white-collar workers in the same industry , of the same sex and age but who did not participate in the health examination and who were asked to complete the same question naires twice . The group that had participated in the health examination did not differ generally from the control group with respect to intra-individual differences as studied in the question naires on the two occasions . This indicates that no deterioration of quality of life or of psychological well-being was experienced by the participants in the health examination We examined changes in five indicators of blood cholesterol awareness in two comparable biracial communities in South Carolina . One community received three years of cholesterol education and intervention activities implemented by a state health department and the other served as a comparison . Cross-sectional , interviewer-administered , r and om digit-dialed telephone surveys of 11,070 adults 18 years and older were conducted in 1987 , 1988 , 1989 , and 1991 . Changes in community levels of knowledge , preventive behavior , risk awareness , and treatment were assessed and compared between the two communities with analysis of covariance techniques that adjusted for age , race , and sex . Significant increases in knowledge , behavior , and risk awareness were observed for most groups defined by race , sex , or age in both communities . Significant net intervention increases between 1987 and 1991 were seen for knowledge of good cholesterol level ( + 16.4 % , P < .001 ) ; behavioral action of ever having blood cholesterol checked ( + 18.6 % , P < .001 ) ; and knowledge of personal level of blood cholesterol ( + 16.0 % , P < .01 ) . These results suggest that a community-wide blood cholesterol screening and education program can be effective in increasing blood cholesterol knowledge , risk awareness , and preventive behavior , thus serving as part of a public health strategy to lower and treat high blood cholesterol levels in a community The Preventive Health Examination ( PHE ) program was design ed to screen for cancer of the lung , colon , skin , and prostate ( or breast ) and to detect the risk factors for coronary artery disease , i.e. , arterial hypertension , hypercholesterolemia , cigarette smoking , and obesity . To investigate the cost-effectiveness of PHE performed by nurse practitioners , the first 176 subjects enrolled in the PHE program at a northeastern , suburban VA Medical Center were evaluated prospect ively . The subjects were recruited through r and om mailing . The direct cost of PHEs was $ 80 per patient . PHEs were performed on 171 men and 5 women , mean age 57.2 years , divided into groups according to the date of evaluation . Nine percent of patients had findings highly suspicious of cancer ( lung nodules in 7 , skin lesions in 9 ) . As a consequence , one patient underwent lobectomy for squamous carcinoma of the lung and another underwent prostatectomy for adenocarcinoma of the prostate . Fifty-five percent of patients had high cholesterol levels , 53 % were obese , 30 % were heavy cigarette smokers , and 19 % were hypertensive . Nineteen percent of the patients had three or more coronary artery disease risk factors . We conclude that low cost PHEs performed by nurse practitioners have a high yield in detecting risk factors for coronary artery disease , and for detecting potentially treatable malignancies Abstract Objectives : To vali date a self administered postal question naire appraising risk of coronary heart disease . To determine whether use of this question naire increased the percentage of people at high risk of coronary heart disease and decreased the percentage of people at low risk who had their cholesterol concentration measured . Design : Validation was by review of medical records and clinical assessment . The question naire appraising risk of coronary heart disease encouraged those meeting criteria for cholesterol measurement to have a cholesterol test and was tested in a r and omised controlled trial . The intervention group was sent the risk appraisal question naire with a health question naire that determined risk of coronary heart disease without identifying the risk factors as related to coronary heart disease ; the control group was sent the health question naire alone . Setting : One capitation funded primary care practice in Canada with an enrolled patient population of about 12 000 . Subjects : R and om sample of 100 participants in the intervention and control groups were included in the validation exercise . 5686 contactable patients aged 20 to 69 years who on the basis of practice records had not had a cholesterol test performed during the preceding 5 years were included in the r and omised controlled trial . 2837 were in the intervention group and 2849 were in the control group . Main outcome measures : Sensitivity and specificity of assessment of risk of coronary heart disease with risk appraisal question naire . Rate of cholesterol testing during three months of follow up . Results : Sensitivity of question naire appraising coronary risk was 87.5 % ( 95 % confidence interval 73.2 % to 95.8 % ) and specificity 91.7 % ( 81.6 % to 97.2 % ) . Of the patients without pre-existing coronary heart disease who met predefined screening criteria based on risk , 45 out of 421 in the intervention group ( 10.7 % ) and 9 out of 504 in the control group ( 1.8 % ) had a cholesterol test performed during follow up ( P<0.0001 ) . Of the patients without a history of coronary heart disease who did not meet criteria for cholesterol testing , 30 out of 1128 in the intervention group ( 2.7 % ) and 18 out of 1099 in the control group ( 1.6 % ) had a cholesterol test ( P=0.175 ) . Of the patients with pre-existing coronary heart disease , 1 out of 15 in the intervention group ( 6.7 % ) and 1 out of 23 in the control group ( 4.3 % ) were tested during follow up ( P=0.851 , one tailed Fisher 's exact test ) . Conclusions : Although the question naire appraising coronary risk increased the percentage of people at high risk who obtained cholesterol testing , the effect was small . Most patients at risk who received the question naire did not respond by having a test . Key messages Of patients at high risk of coronary heart disease , 10.7 % who received a risk appraisal question naire with a general health question naire and 1.8 % of those who received the general health question naire alone had a cholesterol test within the following three months Of patients at low risk , 2.7 % of patients receiving the risk appraisal question naire and 1.6 % of control subjects had a cholesterol test Most patients at risk who received the risk appraisal question naire did not seek a test Further research is needed to identify factors contributing to low uptake of cholesterol testing among people at high risk of coronary heart disease even when encouragement is OBJECTIVE To evaluate cost and benefits of screening for and treating health and lifestyle risks among community-dwelling elderly . DESIGN R and omized controlled trial . SETTING Primary care . PARTICIPANTS An opportunistic and prompted sample of 619 rostered elderly patients presenting for treatment who screened positive . INTERVENTIONS One third ( 209 ) of experimental subjects had screening question naires placed in their charts with concerns highlighted for referrals . Two control groups received usual care . MAIN OUTCOME MEASURES Yearly assessment s of health service use and multidimensional functional capacity . RESULTS Overall , screening and treatment of functionally active , elderly , middle-class people had no significant beneficial effect . Almost half of the experimental sample was ineligible because of treatment noncompliance . Generally ineligible subjects were older and more severely impaired . Subjects 75 years and older with risk factors showed improvement in daily living activities , and those living alone were found to have improved mental health and social functions ( 11 % and 22 % , respectively ) . CONCLUSIONS Screening and treatment was ineffective in improving total functional capacity of all seniors 65 years and older . Elderly people 75 years and older , however , who were living alone or lonely did benefit from screening and treatment showing an improvement in daily activities , mental health scores , and social functions . This finding has implication s for selective preventive health care spending for the elderly . A 2-year follow-up period could be too brief to detect long-term effects of early intervention with younger , middle-class seniors , especially those who are already functionally active Results of a quit-smoking research project in a r and omly selected population . Isacsson , S.-O. and Janzon , L. ( Departments of Clinical Physiology , Social and Preventive Medicine , and Surgery , Allmänna Sjukhuset , S-21401 Malmö , Sweden ) . In the spring of 1973 , 58 strictly r and omized heavy smokers from a defined population of men born in 1914 were asked to quit smoking , at least for 8–9 weeks , as a part of a research project focused upon the relationship between smoking and peripheral blood flow , fibrinolysis , and lung function . Eighty-eight per cent of the smokers were willing to try to quit smoking . Seven ( 12 % ) refused at the outset , as they regarded quitting as impossible . Of the remaining 51 it was possible to keep 31 ( 60 % ) free from smoking for 8–9 weeks with the aid of an intense anti-smoking program lasting 6 weeks . Checks of continued smoking abstention were made by question naire and COHb-determination . After 6 weeks , no further information was given to the subjects . A follow-up after 8–9 months revealed that 33 % of the 51 participants ( i.e. 29 % of the original 58 ) were still non-smokers . The long-lasting effect of our quit-smoking method was equal to the best reported by others and 30 % is probably the highest rate of long-term success to be achieved in smoking cessation OBJECTIVES We evaluated the effectiveness of a community-based participatory research -grounded intervention among women receiving Temporary Assistance for Needy Families ( TANF ) with chronic health conditions in increasing ( 1 ) health care visits , ( 2 ) Medicaid knowledge and skills , and ( 3 ) health and functional status . METHODS We used a r and omized controlled trial design to assign 432 women to a public health nurse case management plus Medicaid intervention or a wait-control group . We assessed Medicaid outcomes pre- and posttraining ; other outcomes were assessed at 3 , 6 , and 9 months . RESULTS Medicaid knowledge and skills improved ( P < .001 for both ) . Intervention group participants were more likely to have a new mental health visit ( odds ratio [ OR ] = 1.92 ; P = .007 ) , and this likelihood increased in higher-risk subgroups ( OR = 2.03 and 2.83 ; P = .04 and .006 , respectively ) . Depression and functional status improved in the intervention group over time ( P = .016 for both ) . No differences were found in routine or preventive care , or general health . CONCLUSIONS Health outcomes among women receiving TANF can be improved with public health interventions . Additional strategies are needed to further reduce health disparities in this population BACKGROUND The Health Education and Research Trial ( HEART ) was a multicenter clinical trial design ed to test methods to improve primary care practice systems for heart disease prevention services . We present the trial methodology , the practice s ' use of medical record tools , and changes in documentation of cardiovascular risk factor screening and management . METHODS Primary care practice s were recruited from 4 Midwestern states . The factorial design result ed in 4 study groups : conference only , conference and quality improvement consultations , conference and prevention coordinator , and all interventions combined . Medical record audits and physician , staff , and patient surveys assessed practice change in cardiovascular disease risk factor documentation . RESULTS Practice s participated fully in this project , set goals to improve preventive services , and implemented recommended medical record tools . The number of goals set and the increase in the use of medical record tools were greatest in the combined intervention group , with improvements noted in all groups . The use of patient history question naires , problem lists , and flow sheets was significantly higher in the combined intervention group when compared with the conference-only group . Documentation of risk factor screening in a recommended-medical record location improved in all intervention groups , with significant sustained improvements in the practice s that received the combined intervention . Documented risk factor management significantly improved in all intervention groups compared with the conference-only control . CONCLUSION Primary care practice s are interested in improving prevention systems and can change these systems in response to supportive external interventions . Promoting organizational change to produce sustained improvement in preventive service clinical outcomes is a complex process that requires further research We evaluated the cost effectiveness of preventive home visits to elderly persons in Denmark alongside a 3-year r and omized controlled study . The main outcome measure was incremental costs per active life-year gained . The number of active life-years was defined as those during which the person is able independently to transfer , walk indoors , go outdoors , walk outdoors in both pleasant and poor weather , and climb stairs . In 17 of 34 municipalities health visitors and general practitioners were offered geriatric training , which focused on early signs of disability , physical activity , and interdisciplinary follow-up . The remaining 17 municipalities offered preventive home visits as usual . Outcomes were measured in 4,034 persons aged 75 or 80 years old and dwelling at home . The difference in mean total costs between the intervention and the control group discounted at 3 % was € −856 ( 95 % CI −2,455 to 744 ) in 75-year-olds and € 694 ( −2,684 to 4,071 ) in 80-year-olds . The discounted difference in mean active life-years was 0.034 ( −0.058 to 0.125 ) and 0.197 ( 0.013 to 0.380 ) , respectively . The study did not provide conclusive evidence on the cost effectiveness of the programs under consideration BACKGROUND Despite increasing evidence that treating dyslipidemia reduces cardiovascular events , many patients do not achieve recommended lipid targets . METHODS To determine whether showing physicians and patients the patient 's calculated coronary risk can improve the effectiveness of treating dyslipidemia in a primary care setting , patients were r and omized to receive usual care or ongoing feedback regarding their calculated coronary risk and the change in this risk after lifestyle changes , pharmacotherapy , or both to treat dyslipidemia . Outcomes , based on intention-to-treat analysis , included changes in blood lipid levels , coronary risk , and the frequency of reaching lipid targets . RESULTS Two hundred thirty primary care physicians enrolled 3,053 patients . After 12 months of follow-up , 2,687 patients ( 88.0 % ) remained in the study . After adjustment for baseline lipid values , significantly greater mean reductions in low-density lipoprotein cholesterol levels and the total cholesterol to high-density lipoprotein cholesterol ratio were observed in patients receiving risk profiles ( 51.2 mg/dL [ to convert to millimoles per liter , multiply by 0.0259 ] and 1.5 , respectively ) vs usual care ( 48.0 mg/dL and 1.3 , respectively ) , but the differences were small ( -3.3 mg/dL ; 95 % confidence interval [ CI ] , -5.4 to -1.1 mg/dL ; and -0.1 ; 95 % CI , -0.2 to -0.1 , respectively ) . Patients in the risk profile group were also more likely to reach lipid targets ( odds ratio , 1.26 ; 95 % CI , 1.07 to 1.48 ) . A significant dose-response effect was also noted when the impact of the risk profile was stronger in those with worse profiles . CONCLUSIONS Discussing coronary risk with the patient is associated with a small but measurable improvement in the efficacy of lipid therapy . The value of incorporating risk assessment in preventive care should be further evaluated OBJECTIVES To evaluate the impact of a new assessment system , the Minimum Data Set for Home Care ( MDS-HC ) , on the functional status and hospitalization rates of frail , community-dwelling older people . DESIGN Single-blind r and omized trial with 1-year follow-up . SETTING Bergamo , Italy . PARTICIPANTS All 187 subjects who were eligible for home care services delivered by two Health Districts between September 1998 and April 1999 . INTERVENTION R and om allocation to an intervention group undergoing MDS-HC assessment or to a control group receiving conventional geriatric assessment with Barthel , Lawton and Brody , and Mini-Mental State Examination ( MMSE ) scales . MEASUREMENTS Hospitalization , health services use and costs , and variations in functional status . RESULTS Survival analysis indicated that the intervention group was admitted to the hospital later and less often than were controls ( relative risk = 0.49 , 95 % confidence interval = 0.56 - 0.97 ) . Health services were used to the same extent , but intervention subjects used more in-home help services . Total costs for the intervention group were 21 % lower than for the control group . The adjusted mean scores of the activities of daily living index ( 51.7+/-36.1 vs 46.3+/-33.7 ; P = .05 ) and MMSE ( 19.9+/-8.9 vs 19.2+/-10.7 ; P = .03 ) were significantly improved in the intervention group as compared with the control group . CONCLUSIONS The MDS-HC assessment instrument may provide a cost-saving approach to reducing institutionalization and functional decline in older people living in the community AIM To evaluate the effect of a cardio-renal screening programme on desired and undue drug use . METHODS Data from the PREVEND cohort ( Prevention of REnal and Vascular ENd-stage Disease ) were used . The drug use of screened ( r and omly ) selected subjects ( n = 2650 ) was compared with unscreened subjects , matched for age and sex ( n = 10 434 ) . Drug use in the overall PREVEND cohort , enriched for albuminuria ( n = 6751 ) , was also studied . Screening-related drugs ( antihypertensive , antilipidaemic , antidiabetic and antithrombotic ) were selected , as well as screening-unrelated drugs ( benzodiazepines , drugs for acid-related disorders and painkillers ) . Time to first prescription after screening is presented as Kaplan-Meier curves . RESULTS After 6.5 years of follow-up , the incidence of drug use was not significantly different between the screened , r and omly selected and unscreened cohorts . Antihypertensives were used by 21.5 and 20.8 % , respectively ; antilipidaemic 12.8 and 10.2 % , antidiabetics 4.0 and 3.9 % , and antithrombotic 11.4 and 12.0 % . Screening-unrelated drugs were used at comparable frequencies . Compared with the unscreened cohort , screening-related drugs were prescribed more frequently for subjects in the enriched cohort ( 25.8 , 15.5 , 5.5 and 13.5 % for antihypertensive , antilipidaemic , antidiabetic and antithrombotic , respectively ) , whereas screening-unrelated drugs were used at comparable frequencies . CONCLUSIONS The incidence of drug use did not differ between the screened , r and omly selected and unscreened cohorts . Screening does not lead to more drug prescription , thus arguing against the fear of undue medicalization after screening . The data also show that , for screening to be successful , it should be performed in a targeted population , such as one enriched for albuminuria Objective – To describe the occurrence of “ health realists ” , “ health pessimists ” and “ health optimists ” in a non-patient population by identifying cases of concordance and discordance between doctor-evaluated health and self-evaluated health and to describe the distribution of selected life-style-related physiological risk factors among these health-groups . Design – Comparative study . Setting – Primary health care . Subjects – 456 middle-aged persons registered with a general practitioner ( GP ) were after a general health screening invited to a health discussion . Prior to the health screening the participants had assigned their health status to one of five categories ranging from “ very poor ” to “ excellent ” . After the health discussion the GP rated the participants ’ general health status on a visual analogue scale . On basis of this information patients were classified as “ health realists ” , “ health optimists ” and “ health pessimists ” . Results – 54 % of the participants could be classified as “ good-health realists ” , 14 % as “ poor-health realists ” , 22 % as “ health optimists ” , and 10 % as “ health pessimists ” . “ Poor-health realists ” had the greatest accumulation of risk factors , followed by “ health optimists ” , “ health pessimists ” and “ good-health realists ” . Among the “ health pessimists ” there was a significantly higher risk score of future cardiovascular disease and poor physical endurance compared with the “ good-health realists ” . Conclusion – Discordance between doctor-evaluated health and self-evaluated health was found in 32 % of the cases studied . “ Health pessimists ” had more risk factors than “ good-health realists ” even though the GPs had rated their general health status as good in both cases Background To assess the feasibility of offering health promotion and preventive medicine initiatives in primary care . Aims A pilot study aim ed at men in general practice to establish the uptake , acceptability and effectiveness of interventions in health initiatives . Methods One thous and men aged 18–65 were selected at r and om from five general practice s in the Western Health Board area . Practice s were r and omly allocated to one of four brief interventions : cardiovascular screening , cancer screening , stress management or general lifestyle advice . Results Fifty-five per cent of men responded , with 35.7 % actually attending . There were minor but significant short-term changes in health status and behaviours . Participants expressed high levels of satisfaction , but tended to prefer interventions with an explicit clinical component . Conclusion It is at least as feasible to offer health promotion for men in primary care as it is for other demographic groups , but adequate training and re sources are required OBJECTIVE : To examine the effects of a GP exercise referral programme on modifiable coronary heart disease risk factors . DESIGN : R and omised controlled trial . A battery of vali date d measures were carried out at 0 , 8 , 16 , 26 , and 37 weeks . SETTING : Two community health centres and a leisure centre in Hailsham , East Sussex . SUBJECTS : 389 patients ( smokers , hypertensive or overweight ) were selected from medical records , screened for contraindications to exercise and 345 were invited into the study . Of 142 patients r and omly allocated , 40 ( 41 % ) completed the study in the exercise group and 31 ( 69 % ) in the control group . Sixty ( 35 % ) invited smokers ( 48 % of non-smokers ) , 71 ( 38 % ) invited hypertensive patients ( 45 % of non-hypertensive patients ) , and 107 ( 45 % ) overweight patients ( 33 % of non-overweight patients ) were r and omised . Of those r and omised , 27 ( 45 % ) smokers , 52 ( 48 % ) overweight , and 43 ( 61 % ) hypertensive patients completed the study . INTERVENTION : The exercise group was offered 20 , half price sessions over 10 weeks at a leisure centre . Patients engaged in moderate and vigorous aerobic type activity on various exercise machines , in a semi-supervised , informal environment . RESULTS : 87 % of those referred used the prescription and 28 % ( high adherers)(45 % of obese patients ) did at least 15 sessions . The exercise group reduced sum of skinfolds by 8.1 % ( 2.9 to 13.3 , 95 % confidence intervals ) more than the control group , up to 16 weeks after baseline . High adherers reduced sum of skinfolds by 9.2 % ( 0.9 to 17.5 ) more than the control group , up to 26 weeks . High adherers reduced systolic blood pressure by 7.2 % ( -0.7 to 14.9 ) ( that is , 9 mm Hg ) more than low adherers , up to 37 weeks . Non-smokers and obese patients attended more prescribed sessions than smokers and non-overweight patients . CONCLUSIONS : Reduction in sum of skinfolds was maintained up to 26 weeks , among high adherers compared with controls . Reduction in systolic blood pressure was evident up to 37 weeks among high adherers , but only in comparison with low adherers . Selection of appropriate referees and use of other strategies to improve exercise adherence will help to maximise the benefits from GP exercise prescription schemes A r and omized controlled trial of geriatric screening and surveillance was undertaken on a practice population of 295 patients aged 70 years or more over a two-year period . In the screened group ( 145 patients ) many social problems were found and a total of 380 medical conditions were reported during the study period , 144 ( 38 per cent ) of which were previously undetected . Conditions found most frequently involved the circulatory , musculoskeletal and nervous systems ; 67 per cent of the conditions found were manageable , half being improved and the remainder resolved completely . The screening programme was found to increase the use of social and health services but it did also decrease the expected duration of stay in hospital . Independent assessment of patients in the study and control groups at the end of the two-year period showed that the screening programme had made no significant impact on the prevalence of socio-economic , functional , and medical disorders affecting health . We formed the firm impression that the study patients were made more comfortable ( by control of pain ) and less disabled , although there was no unequivocal objective evidence of this . They were , however , kept independent for longer . The findings are discussed and a model of geriatric care is suggested combining conventional management on dem and with comprehensive screening to identify the high-risk patients on whom care might need to be focussed INTRODUCTION About 90 % of Polish adults with hypercholesterolemia are not aware of their disease or are not treated . OBJECTIVES The aim of the study was to evaluate hypercholesterolemia control in general practice and to assess the implication s of introducing the nationwide Program of Cardiovascular Disease Prevention ( PCVDP ) . PATIENTS AND METHODS Sixty-six primary care clinics were scheduled to participate in the study . In half of them , PCVDP was implemented ( active clinics ) , the remaining 33 constituted the control group . Study participants were selected from a group of persons aged 35 - 55 years with medical records established before January 1 , 2005 . Patients with coronary heart disease , stroke , or peripheral atherosclerosis were excluded . In a r and om sample of patients scheduled for the study , medical records were review ed followed by an interview , physical examination , and blood lipid tests . RESULTS The availability of data on total cholesterol ( TC ) levels increased from 19.2 % to 40.5 % in patients from the active clinics and did not change in the control group . Hypercholesterolemia treatment was reported more often in the active clinics than in the control group ( 4.4 % and 3.3 % , respectively , P < 0.01 ) . Patients from the active clinics more often reported that a physician informed them about increased TC levels compared with the control group ( 29.1 % and 24.1 % , respectively , P < 0.01 ) . However , the percentage of patients with increased TC or low-density lipoprotein cholesterol levels and those using statins did not differ between the study groups . CONCLUSIONS PCVDP is an effective tool to identify subjects with hypercholesterolemia but has no effect on the rate of achieving the recommended treatment targets Abstract Objectives : To determine the effectiveness of a health check and assess any particular benefits result ing from feedback of plasma cholesterol concentration or coronary risk score , or both Design : R and omised controlled trial in two Glasgow work sites Subjects:1632 employees ( 89 % male ) aged 20 to 65 years . Interventions : At the larger work site , ( a ) health education ; ( b ) health education and feedback on cholesterol concentration ; ( c ) health education and feedback on risk score ; ( d ) health education with feedback on cholesterol concentration and risk score ( full health check ) ; ( e ) no health intervention ( internal control ) . At the other work site there was no health intervention ( external control ) . Main outcome measures Changes in Dundee risk score , plasma cholesterol concentration , diastolic blood pressure , body mass index , and self reported behaviours ( smoking , exercise , alcohol intake , and diet ) in comparison with internal and external control groups Results : Comparisons between the full health check and the internal control groups showed a small difference ( 0.13 mmol/l ) in the change in mean cholesterol concentration ( 95 % confidence interval 0.02 to 0.22 , P=0.02 ) but no significant differences for changes in Dundee risk score ( P=0.21 ) , diastolic blood pressure ( P=0.71 ) , body mass index ( P=0.16 ) , smoking ( P=1.00 ) , or exercise ( P=0.41 ) . Significant differences between the two groups were detected for changes in self reported consumption of alcohol ( 41 % in group with full health check v 17 % in internal control group , P=0.001 ) , fruit and vegetables ( 24 % v 12 % , P<0.001 ) , and fat ( 30 % v 9 % , P<0.001 ) . Comparison of all groups showed no advantage from feedback of cholesterol concentration or risk score , or both . Conclusions : The health check only had a small effect on reversible coronary risk . It was effective in influencing self reported alcohol consumption and diet . Feedback on cholesterol concentration and on risk score did not provide additional motivation for a change in behaviour Objectives - To evaluate changes in plasma cholesterol following health screening and health discussion s in general practice . Design - R and omised prospect i ve population -based study conducted over a period of 5 years . Setting - Primary care , all general practitioners ( GPs ) in a welldefined area . Subjects - A r and om sample of inhabitants aged 30 - 49 years in January 1991 , registered with a local GP was invited to participate . The participants ( 1507 persons , or 75.4 % of the 2000 invited ) were r and omly allocated to two intervention groups and a control group . Main outcome measures - Plasma cholesterol , percentage of subjects with plasma cholesterol higher than 7 mmol/l . Results - After 5 years of intervention , plasma cholesterol in the whole population was significantly lower in the intervention groups compared to the control group . The decrease was most pronounced ( 0.5 mmol/l ) in subjects at high cardiovascular risk . The percentage of high-risk individuals with a cholesterol level higher than 7 mmol/l was significantly lower in the intervention groups compared to the control group ( 9.8 % vs 6.2 % , p = 0.04 ) , corresponding to a 37 % reduction . Conclusions - The study shows that the health checks had a measurable impact on plasma cholesterol levels , the most pronounced effect is seen among individuals at high cardiovascular risk The Kaiser Permanente Multiphasic Evaluation Study is often cited as evidence from a r and omized trial that screening sigmoidoscopy reduces mortality from colorectal cancer . To examine the role of sigmoidoscopy in this reduction , we review ed the 110 incident cases of colorectal cancer occurring among the 10,713 subjects from r and omization in 1964 through 1982 . Tumor stage at diagnosis , location , mode of discovery , and current mortality status were determined for each . We also reanalyzed chart review data for the years 1965 through 1974 to assess the difference in exposure to sigmoidoscopy between groups . Study group subjects , who were urged to have annual multiphasic health checkups ( MHC ) , had both a lower cumulative incidence ( 4.3 vs 6.7 cases per 1000 persons ) and a better stage distribution ( 86 vs 54 % Stage B or better ) than nonurged control subjects for colorectal cancers arising within reach of the sigmoidoscope . The lowered incidence accounted for two-thirds of the total difference in mortality . No appreciable difference in removal of colorectal polyps was seen between groups . Only a slight excess in exposure to sigmoidoscopy was seen in the study group ( 30 vs 25 % of subjects examined at least once between 1965 and 1974 ) , which was unlikely to account for more than a small fraction of the study group 's decrease in mortality . Although the Multiphasic Evaluation Study did find a significantly lower mortality from colorectal cancer in the study group , it did not achieve a substantial difference in exposure to sigmoidoscopy . Its results are therefore inconclusive with respect to sigmoidoscopy and should not be used as evidence either for or against sigmoidoscopic screening OBJECTIVES To measure the extent to which changes in cardiovascular risk factors were correlated among married couples following a 1-year primary care , family-centered , cardiovascular lifestyle intervention program and to identify couples who benefited most from this prevention program . DESIGN Observational study . SETTING Thirteen primary care centers in 13 towns in Britain . PARTICIPANTS A total of 1477 men aged 40 to 59 years and their female partners who attended a family health checkup in 1991 to 1992 from r and omly ordered invitations to registered families . After 1 year , 1204 ( 82 % ) partner pairs were rescreened . MAIN OUTCOME MEASURES One-year changes in cigarette smoking , systolic blood pressure , serum cholesterol level , blood glucose level , and a total coronary risk score . RESULTS Comparing men and women partners , baseline values and 1-year changes in overall coronary risk score ( Pearson r = 0.27 and r = 0.20 , respectively ) , cigarette smoking , body mass index , systolic blood pressure , cholesterol levels , and glucose levels were all positively correlated ( all P < .001 except smoking cessation , P = .03 ) . Changes in cholesterol levels and systolic blood pressure were also associated with partner 's baseline measurement ( P < or = .01 in both men and women ) . CONCLUSIONS Men and women who benefit most from risk factor reductions have partners who also tend to benefit most . Conversely , men and women who enjoy little or no benefit have partners who tend to have similarly small benefits . It is likely that lifestyle intervention targeted at men and women as couples rather than as individuals may result in a greater reduction in cardiovascular risk factors , possibly through mutual reinforcement of lifestyle changes OBJECTIVE To test the effectiveness of a patient-initiated , touch-sensitive computer system ( TSCS ) for improving screening rates for cancers of the breast , cervix , colon and rectum , and oral cavity . DESIGN One-year , r and omized , controlled trial with primary care practice as the unit of analysis . SETTING Sixty primary care practice s , r and omly recruited from 329 nonteaching practice s in a southeastern state . SUBJECTS R and om sample of the medical records of 50 male and female adult patients before intervention and 50 adult patients after intervention in each practice and a r and om sample of 507 TSCS users . INTERVENTIONS Touch-sensitive computer system and a registered nurse who served as liaison to the study practice s. The TSCS provided patient-specific preventive service recommendations and facilitated work flow to increase the completion of these interventions . MAIN OUTCOME MEASURE Average change , adjusted for health maintenance examination ( HME ) and use of the TSCS , in the proportion of eligible patients undergoing screening mammography , clinical breast examination , digital rectal examination , fecal occult blood test , flexible sigmoidoscopy , Papanicolaou smear , and oral cavity examination . RESULTS We observed a significant increase in the completion of screening mammography ( 6.6 % ; P < or = 0.5 ) and clinical breast examination ( 6.1 % ; P < or = .01 ) in women 50 years of age and older , particularly for those who had an HME during the study year . CONCLUSIONS Patients who have HMEs are more likely to receive cancer screening ; however , a computer-based system for preventive services can contribute to improvement in screening . Among those patients who did not have an HME , TSCS users had higher rates of breast cancer screening than nonusers A study was carried out to investigate people 's interest in participating in health check-up and in discussion s about health with their own general practitioner , participants ' health status , the proportion who received health advice following health check-up , and the lifestyle goals they set following discussion with their general practitioner . This study reports the baseline data from a five-year r and omized , controlled , prospect i ve , population -based study in general practice s in Ebeltoft , Denmark . All general practitioners from the four practice s in Ebeltoft and a r and om sample of 2,000 people aged between 30 and 50 years were invited to participate . Participants were r and omly divided into three groups-one control group and two intervention groups . One intervention group was given a health check-up which included a range og tests ( Table 2 and 3 ) ; this group received written feedback from the general practitioner . The other intervention group was also given a health check-up and written feedback , in addition , they were given the opportunity to attend their general practitioner to discuss health-promoting measures . A total of 1370 people participated in the study ( 69 % response rate ) . Health advice was given to 76 % of 905 participants following health check-up . Almost all of the 456 participants ( 96 % ) who were offered the opportunity of discussing their health with their general practitioner took up the offer : 64 % of the 456 participants reported that they had decided to undertake lifestyle changes . Eleven of those who discussed their health with the doctor were referred to a specialist ( 2 % ) . There was considerable interest in participating in health promotion . Three out of four of those who had a health check-up were given health advice . Two out of three of those who were offered a health talk with the general practitioner appeared willing to make relevant lifestyle changes . Longterm follow up is needed to determine effects and side effects of health check-up and health talks OBJECTIVES We assessed the effect of the Comprehensive Annotated Reminder Tool ( CART ) on physician adherence to preventive services recommendations . STUDY DESIGN Using a r and omized pretest/posttest control group design , we assigned physicians to the CART group or the control group , followed up prospect ively , and evaluated for appropriate adherence to guidelines . The 3 age-specific versions of the CART annotated history and physical examination form contained up to 49 preventive services recommendations . POPULATION All resident physicians in a large family practice residency program were studied over the course of 1 academic year . OUTCOMES MEASURED We performed blinded chart review s to assess the appropriateness of preventive services ordered by the physicians before the introduction of the CART , during its use , and after its removal . A multiple-choice test completed before and after the use of the CART forms assessed knowledge . RESULTS When the CART was used , the appropriateness of physician preventive behavior increased by 21 % overall . The appropriateness of history , physical examination , and laboratory interventions increased by 33 % . When the CART was removed , physician behavior returned to baseline ( P < or = .0025 for 16 of 20 interventions ) . No significant differences were observed in the control group over time . Knowledge increased over the study period for all physicians ( P < or = .005 ) but did not differ significantly between the treatment and control groups ( P = .608 ) . CONCLUSIONS Use of the CART significantly improved physician performance in the appropriate delivery of preventive care Data are reported concerning social responses to health checks in an occupational setting . Previous research has suggested that screening may be a stressful experience . This , in turn , has contributed to a degree of scepticism about the value of health checking . No evidence was found in the present study to support the proposition that health checks cause such responses . It is shown that health checks prompt recipients to try to engage in health promoting behavioural changes . The study was a r and omized controlled trial of 1,371 persons employed in a large engineering factory in the West of Scotl and OBJECTIVES --To assess the effect of preventive home visits by public health nurses on the state of health of and use of services by elderly people living at home . DESIGN --R and omised controlled trial . SETTING --General population of elderly people in one of the southern regions of the Netherl and s. SUBJECTS--580 subjects aged between 75 and 84 years r and omly allocated to intervention ( 292 ) or control ( 288 ) group . INTERVENTIONS --Four visits a year over three years in intervention group . Control group received no home visits . MAIN OUTCOME MEASURES --Self rated health , functional state , well being , loneliness , aspects of the mental state ( depressive complaints , memory disturbances ) , and mortality . Use of services and costs . RESULTS --Visits had no effect on the health of the subjects . In the group visited no higher scores were seen on health related measures , fewer died ( 42 ( 14 % ) v 50 ( 17 % ) ) , and community care increased slightly . In the control group more were referred to outpatient clinics ( 166 ( 66 % ) v 132 ( 55 % ) ) , and they had a 40 % increased risk of admission ( incidence rate ratio 1.4 ; 90 % confidence interval 1.2 to 1.6 ) . No differences were found in long term institutional care , and overall expenditure per person in the intervention group exceeded that in the control group by 4 % . Additional analyses showed that visits were effective for subjects who initially rated their health as poor . CONCLUSIONS --Preventive home visits are not beneficial for the general population of elderly people living at home but might be effective when restricted to subjects with poor health In a study of older enrollees in an HMO , we found that seniors who are higher users of health care services are willing to participate in health promotion programs . Although people aged 85 or older and those with chronic diseases are slightly more reluctant to participate , they are willing to make additional visits for health promotion purpose s. Close proximity to the clinic and support from their family physician are important correlates of participation South-East London Screening Study Group ( Department of Community Medicine , St Thomas 's Hospital and Medical School , London SE1 1EH , Engl and ) . A controlled trial of multiphasic screening in middle-age : results of the South-East London Screening Study . International Journal of Epidemiology 1977;6:357 - 63 . The results of a controlled trial of multiphasic screening in general practice are presented . In 1967 , 7229 individuals aged between 40 and 64 years were r and omly allocated into either a Screening or Control group . The Screening group were invited to attend two screening sessions held about two years apart , while the Control group continued to receive conventional medical care . Both groups were then invited to undergo a health survey in 1972 - 73 which revealed no significant differences in morbidity between the two groups . Careful follow-up permitted detailed Screening-Control comparisons of various outcome measures -consultation and hospital admission rates , certified sickness absence from work , and mortality . Nine years after the initial screening , no significant differences were found between the two groups in any of the outcome measures . It is estimated that a similar screening programme for the entire middle-aged UK population would cost 142 million pounds at 1976 prices OBJECTIVES 1 . To compare a patient-centred , self-directive intervention with conventional care ; 2 . To evaluate longitudinal within-group changes of coronary heart disease risk . METHODS Risk factor changes were evaluated in 110 men with high coronary heart disease risk attending a one year intervention study in general practice . The 22 participating general practice centres were r and omly allocated to follow either a patient-centred , self-directive intervention or a conventional approach . RESULTS No significant between-group differences were found in any single risk factor or in the combined risk of coronary heart disease . The improvement of total risk from screening time to conclusion of the study corresponded with changes of relative risks of CHD to 0.64 ( 95 % CI : 0.54 - 0.77 ) and 0.65 ( 0.54 - 0.77 ) in the patient-centred , self-directive and the conventional care group respectively ( p < 0.0001 in both groups ) . CONCLUSION Everyday general practice clinical work seems as efficacious as a specific intervention method based on currently advocated behaviour change principles BACKGROUND The Well-Integrated Screening and Evaluation for Women Across the Nation ( WISEWOMAN ) project addresses the need for effective cardiovascular disease ( CVD ) prevention among underserved , midlife women . We describe an Enhanced Intervention that addressed environmental and individual factors within the context of a clinic-based intervention . We also present the study design and baseline results of the r and omized trial to evaluate the enhanced intervention . METHODS The multicomponent behavior change intervention addressed many elements of the Chronic Care Model ( CCM ) , including the community re sources and policy element , wherein Enhanced Intervention participants were encouraged to overcome environmental barriers to a healthy lifestyle by using community re sources . Study participants were enrolled at one community health center ; all were low-income , underinsured , midlife ( 40 - 64 years ) women . RESULTS A total of 236 participants were r and omized to receive the Enhanced Intervention or the Minimum Intervention . At baseline , over three fourths of the participants were overweight or obese . Participants reported a variety of problematic neighborhood characteristics , including a paucity of restaurants with healthy food choices ( 41 % reported as a problem ) ; not enough farmer 's markets or produce st and s ( 50 % ) , not enough affordable exercise places ( 52 % ) , not enough physical activity programs that met women 's needs ( 42 % ) , heavy traffic ( 47 % ) , and speeding drivers ( 53 % ) . Overall , women knew little about affordable exercise venues and nutrition classes . CONCLUSIONS In this clinic-based intervention , we addressed environmental factors related to a healthy lifestyle . Results indicate the need for effective and feasible intervention strategies to address the environments in which individuals are making behavior changes . The effectiveness of the WISEWOMAN Enhanced Intervention will be assessed in a r and omized trial The purpose of this research was to examine the effect of a multifactorial intervention to prevent falls by increasing self-efficacy to prevent falls , improving the knowledge of medication safety , and decreasing the number of environmental risks in older persons dwelling in the community . A sample of 120 cognitively intact residents of this community who were 65 years of age and older were recruited into a two-group pretest-post-test experimental design and r and omly assigned to an experimental group and a comparison group ( 60 in each group ) . The intervention was delivered , and data were collected during three home visits in a 4-month period . ( 1 ) Experimental subjects improved their fall self-efficacy , environmental safety , and knowledge of medication safety significantly ( p < 0.01 ) as compared with those in the comparison group at post-test ; ( 2 ) the incidence of falls was reduced at post-test in both groups compared to pretest scores , and the falling was more serious in the comparison group at post-test compared to that in the experimental group . The results can help community health professionals to individualize their interventions to the specific needs of the elderly , thus helping to prevent falls among community-dwelling elders Physicians endorse prevention but provide only low levels of screening , health counseling , and immunization . Between 1981 and 1986 , a r and omized controlled trial was conducted at the Seattle ( Wash ) Veterans Affairs Medical Center to assess the effectiveness of the following three methods of delivery of preventive services : ( 1 ) a physician-oriented model that includes education and motivation , a chart flowsheet listing recommended activities , and periodic feedback about performance ; ( 2 ) a patient education model in which patients were mailed an informative brochure advising them to ask physicians for preventive services as depicted in a patient-held pocket guide ; and ( 3 ) a health promotion clinic that patients were invited to attend . A control group received their usual care . A total of 1224 male out patients were enrolled in the trial . Baseline prevention rates for 12 age-specific prevention activities were below 25 % . Neither the control group rates during the 5-year trial nor the rates for the two educational models , either singly or as a combined intervention , changed . Only the health promotion clinic model was effective , tripling prevention rates in its first year and sustaining these levels for all 5 years . It is difficult to change the clinic roles of experienced physicians and their long-term patients in a specialized multiclinic setting . Providing a separate health promotion clinic option is popular with patients , bypasses gatekeeper barriers , is reasonable in cost , and warrants wider application The PreFord Study is a multicenter prospect i ve cohort study to evaluate guideline based risk management on primary prevention of cardiovascular diseases . Furthermore a r and omised controlled trial ( RCT ) will be design ed to analyse the effect of a special intervention program . 40,000 employees of the Ford Motor Company , Visteon Company and Deutz Company in Germany will be included , monitored for ten years and the following primary endpoints will be investigated : 1 . evaluation and comparison of established and newly developed risk-scores , 2 . the relative impact of single and combined cardiovascular risk factors on cardiovascular diseases , 3 . the influence of a novel occupationally integrated ambulant rehabilitation program in combination with a guideline oriented optimal drug therapy within a high risk group on the primary endpoint : risk reduction by , 4 . the influence of this intervention on secondary endpoints : death , myocardial infa rct ion and stroke , combined appearance of angina pectoris and hospitalisation , occurrence of cerebral circulatory disorder and hospitalisation , occurrence of peripheral occlusive arterial disease and hospitalisation and single cardiovascular risk factors and cost-benefit- analysis . Beginning with an cross sectional study there will be a systemic screening of cardiovascular risk profiles , of anthropometric data and different lifestyle-factors . Based on these data participants will be differentiated into three risk-groups according to the risk score of the European Society of Cardiology ( risk of a lethal primary acute cardiovascular event : I < or = 1 % ; II > 1- < 5 % and III > or = 5 % ) . In the following longitudinal study different strategies will be applied : Group I : low risk ( < 0.5 % per year ) : repetition of the investigation after five and ten years . Group II : middle risk , ( 0.6 % to 1.4 % per year ) , repetition of the investigation every two years , instruction of the patients general practitioner ( GP ) with respect to a risk factor oriented and evidence based treatment . Group III : high risk , ( > 1.5 % per year or > 15 % within the next 10 years ) will be r and omised into two interventional groups . The first one , the intervention-group " PreFord " will perform an occupational integrated rehabilitation program ( 2,5 - 3 hours twice a week , for 15 weeks according to the BAR guidelines ) with a following engagement in heart-groups and an annual repetition of the check-ups . The second group , the " classic " intervention-group will be treated evidence based in cooperation with their GP . As a result of this long term interventional study efficient , area wide implementable and economically feasible prevention concepts with special regards to operational healthcare will be developed and evaluated . Core elements will be exercise- and lifestyle-oriented concepts as well as guideline -based pharmacotherapy The Health Care Financing Administration ( HCFA ) funded a series of demonstration programs to learn about the implication s of extending coverage for disease prevention/health promotion services to Medicare beneficiaries . This article examines the use of such services by a rural population under this demonstration program . Individuals enrolled in the demonstration were eligible for specific risk reduction interventions . They were enrolled in one of two groups : ( 1 ) a hospital-based group in which hospitals were paid a capitated fee for providing all services and ( 2 ) a physician-based group in which physicians were paid fee-for-service for providing each service . Chi-square tests of association as well as logistic regression models were used to assess whether eligibility for services , and use of services by those eligible , varied by group and by sociodemographic characteristics . Forty-one percent were eligible for a nutrition program , 11 % for smoking cessation , 2 % for alcohol counseling , and 7 % for dementia/depression evaluations . Participation in the programs varied across the programs and within programs by gender , education , and group assignment . Older rural Americans will use some disease prevention/health promotion services if they are covered by Medicare . Use will be higher among those with more education . Rural beneficiaries are more likely to use preventive services if encouraged to do so by their doctors rather than by hospital-based programs Abstract In 1964 a controlled trial was initiated to evaluate the effectiveness of a program of urging subjects to take periodic multiphasic health checkups ( MHC 's ) in preventing or postponing morbidity , disability , and mortality . A group of over 5000 Kaiser Foundation Health Plan members aged 35–54 at entry to the study has been urged to take MHC 's annually . Along with a comparable group of members not so urged , these subjects have been followed for 11 years . Use of outpatient clinic services , other than those services forming part of the MHC was similar in the urged ( study ) group and in non-urged ( control ) group . Overall , hospital use was also similar in the two groups . There was no difference between the overall groups in self-reported disability . However , selfreported disability was significantly less common in the older study group men ( aged 45–54 at entry ) , largely due to less disability from hypertension complications , ischemic heart disease , and back conditions . This provides a hypothesis as to a beneficial effect in a specific age-sex group that should be tested further . Mortality from a set of conditions hypothesized in advance to be most postponable or preventable through periodic MHC 's was significantly lower in the study group as a whole , primarily due to fewer deaths from hypertension complications and colorectal cancer . On the other h and , suicides and lympho-hematopoietic cancer deaths were significantly more common in the study group , though re analysis of the data revealed little relationship between these latter death rates and actual MHC exposure . Total mortality , from all causes combined , was slightly lower in the study group , but this difference was not statistically significant . Though the prevalence of a number of disability and mortality risk factors was somewhat higher in the control group at entry , adjustment for these differences did not eliminate the statistically significant control group excesses in disability ( older men only ) and potentially postponable cause mortality . With regard to processes by which increased study group MHC exposure may have caused the observed health outcome differences , there was more identification and treatment of hypertension , hyperlipidemia , cigarette smoking , obesity , and diabetes in the study group , though the differences were not large . There also was a trend toward earlier diagnoses of colorectal cancer in the study group , due mostly to MHC-related sigmoidoscopy . When the economic impact of all major health-related events was estimated for the older men in the 1965–1975 period , there was a net difference of over $ 2100 per man , favoring the study group . The health outcome rates for the women and the younger men indicated that there would be no savings for these other study group subjects , were similar cost analyses to be made Physicians ' performance of the periodic health examination is often incomplete . Performance rates may be low because physicians forget recommendations for specific periodic health examination components at the time of the patient encounter . We studied the effect of providing information about seven periodic health examination actions ( cervical Pap smear , mammography , fecal occult blood testing , serum cholesterol level , and influenza , pneumococcal , and diphtheria-tetanus immunizations ) on first-year medical residents ' performance of these actions over a three-month period . We r and omly selected 16 residents to receive periodic health examination recommendations , plus data supporting each recommendation , on their outpatient charts at the patient encounter . Thirteen residents who did not receive this information served as controls . Experimental and control groups achieved similar knowledge scores ( 0.53 versus 0.47 , P = .48 ) and attitude scores ( 0.73 versus .078 , P = .19 ) for preventive care measures on pre study testing . The experimental group performed 10.5 % of indicated periodic health examination actions , whereas the control group performed 5.8 % of indicated actions ( P = NS ) . These results suggest no clinical ly meaningful improvement in performance of periodic health examination actions , even when periodic health examination guidelines were available at the time of the physician-patient encounter BACKGROUND The aim of this study was to investigate the long-term effects of one general health screening on mortality . METHOD After stratification and r and omization of a population of 450,000 inhabitants , two groups were formed , an intervention group of 3064 people and a control group of 29,122 people . From the National Cause of Death Register , data were collected as regards death and causes of deaths for 1970 - 1990 . RESULTS Multivariate analysis was used to correct for known confounders . We then found no differences between the groups regarding deaths from all causes , cardiovascular diseases , cancer or accidents and poisoning . CONCLUSIONS One general health screening seems to have little , if any value in preventing fatal diseases BACKGROUND Despite the imminent expansion of Medicaid coverage for low-income adults , the effects of exp and ing coverage are unclear . The 2008 Medicaid expansion in Oregon based on lottery drawings from a waiting list provided an opportunity to evaluate these effects . METHODS Approximately 2 years after the lottery , we obtained data from 6387 adults who were r and omly selected to be able to apply for Medicaid coverage and 5842 adults who were not selected . Measures included blood-pressure , cholesterol , and glycated hemoglobin levels ; screening for depression ; medication inventories ; and self-reported diagnoses , health status , health care utilization , and out-of-pocket spending for such services . We used the r and om assignment in the lottery to calculate the effect of Medicaid coverage . RESULTS We found no significant effect of Medicaid coverage on the prevalence or diagnosis of hypertension or high cholesterol levels or on the use of medication for these conditions . Medicaid coverage significantly increased the probability of a diagnosis of diabetes and the use of diabetes medication , but we observed no significant effect on average glycated hemoglobin levels or on the percentage of participants with levels of 6.5 % or higher . Medicaid coverage decreased the probability of a positive screening for depression ( -9.15 percentage points ; 95 % confidence interval , -16.70 to -1.60 ; P=0.02 ) , increased the use of many preventive services , and nearly eliminated catastrophic out-of-pocket medical expenditures . CONCLUSIONS This r and omized , controlled study showed that Medicaid coverage generated no significant improvements in measured physical health outcomes in the first 2 years , but it did increase use of health care services , raise rates of diabetes detection and management , lower rates of depression , and reduce financial strain Background R and omised , controlled trials focusing on long-term psychological reactions to information about increased risk of coronary heart disease are scarce . Design A population -based r and omised , controlled , 5-year follow-up trial was conducted in general practice . Methods In 1991 , invitations were sent to 2,000 middle-aged people registered in the general practice s in the district of Ebeltoft , Denmark . A total of 1,507 ( 75.4 % ) agreed to participate and were r and omised into a control group and two intervention groups : one included health screening , a written feedback and an optional follow-up visit with the general practitioner ; the other included health screening , written feedback and a planned 45-min follow-up visit with the general practitioner . The participants were informed at screening about their risk of developing coronary heart disease . Psychological distress was measured by the GHQ-12 before screening and at the 1 and the 5-year follow-up . Results Before the screening ( 0 year ) , 1 and 5 years after there were no significant differences in the GHQ-12 score between the control group and the two intervention groups . Nor were there any differences related to information about increased risk of coronary heart disease between scores obtained at the 1 and the 5-year follow-up . Conclusion Middle-aged persons had no long-term psychological reaction after information about increased risk of developing coronary heart disease following a health screening in general practice evaluated by the GHQ-12,1 year and 5 years after the examinations OBJECT To discover how attempts to increase the delivery of preventive services affect clinician satisfaction . METHODS The IMPROVE project was a r and omized clinical trial conducted in 44 clinics in and around Minneapolis-St . Paul , Minnesota . Personnel were trained in continuous quality improvement techniques to organize preventive services delivery systems . Satisfaction with delivery of these services and with the sponsoring organizations was measured before the intervention ( Time 1 ) , at the end of the intervention ( Time 2 ) , and 1 year post-intervention ( Time 3 ) . RESULTS At no time was the intervention associated with a change in the respondents satisfaction with their places of work or with their job roles . Satisfaction with preventive services delivery increased from Time 1 to Time 3 among intervention-clinic respondents . Satisfaction with the IMPROVE project and the efforts of the two managed care organizations to help the clinics deliver preventive services peaked at Time 2 and declined toward baseline at Time 3 . Satisfaction with preventive services delivery tended to increase more in the 13 intervention clinics that implemented a preventive services delivery system than in the nine intervention clinics that did not implement a preventive services delivery system ( p = 0.15 ) . CONCLUSIONS Planned organizational change to create systems for preventive services delivery can be associated with increased clinician satisfaction with the way these services are delivered . However , increased satisfaction with preventive services does not necessarily indicate that service delivery rates have increased OBJECTIVES This study was undertaken to test the acceptability of preventive services under Medicare waivers to a community-dwelling population aged 65 and over and to examine the effect of such services on health . METHODS Medicare beneficiaries and design ated primary care providers were sample d , and beneficiaries were screened and surveyed . A total of 4195 individuals were then r and omized into intervention or control groups . Those in the intervention group were offered free preventive visits ( under waivers ) to their physicians . A follow-up survey of the entire group was administered after completion of the intervention . RESULTS Sixty-three percent of the intervention group made a preventive clinical visit , and about half of them a counseling visit . For men , being married and having a solo practitioner were positively associated with accepting the intervention services , while for women , having had a mammogram , having a confidant , having a high school education , and having a female practitioner were so associated . The intervention group showed a greater health benefit than did the control group and had a significantly lower death rate : 8.3 % vs 11.1 % . CONCLUSIONS Older individuals will respond to preventive programs , and such services will result in modest health gains AIM To evaluate the effect of a letter intervention that was send to both the participants of a population screening and their general practitioners . We also tested what predicting variables influenced the GP to actually prescribe blood pressure lowering drugs ( BPLD ) or lipid lowering drugs ( LLD ) . METHOD The study design was cross sectional , in the PREVEND outpatient clinic in Groningen University Hospital , the Netherl and s. We used the clinical data of the 8592 subjects that participated in the first screening of the PREVEND study . Data on drug use was collected from community pharmacies . Drug use was measured the year before and after the screening with the subsequent intervention letter . As control population without intervention , we used the data from the InterAction Data Base ( IADB ) st and ardized for the population characteristics of the intervention group . The letter intervention was sent to participants who had shown after screening to have either an elevated blood pressure or plasma cholesterol , and the letter contained the advice to use a BPLD or LLD . Main outcome measures were proportion of patients prescribed BPLD and /or LLD in the year before and after the intervention , and variables that influence the GP to prescribe BPLD and LLD . RESULTS Data from the community pharmacy were available from 7567 ( 88 % ) subjects . 397 participants ( 5.2 % ) received a letter with advice to start a BPLD , and 326 participants ( 4.3 % ) received a letter with advice to start a LLD . The prevalence of patients who were using BPLD and LLD before the intervention was not significantly different between the intervention and control group , 16.6 ( CI 95 % 15.8 -17.5 ) vs 16.0 and 4.8 ( 4.4 - 5.3 ) vs 4.6 , respectively . After the letter intervention , the prevalence of BPLD use was higher in the intervention group compared with the control group ( 19.4 [ 18 , 5 - 20 , 3]vs 17.0 % ) , as was the prevalence of LLD use ( 7.1[6.5 - 7.7 ) vs 5.4 % ) . The same held true for the incidence of BPLD ( 3.4[3.0 - 3.8]vs 2.5 % ) and LLD use ( 2.1 [ 1 , 6 - 2 , 4]vs 1.0 % ) , respectively , in the year after the intervention . Univariate and multivariate analysis showed that a higher blood pressure and cholesterol level , but not the presence of other cardiovascular risk factors , were associated to with a greater percentage use of a BPLD and a LLD . CONCLUSION A population survey followed by a letter of intervention to both the patient and GP are effective to improve the use of blood pressure and lipid lowering drugs as a primary prevention in patients with hypertension and hyperlipidemia . Our therapeutic advice however , was followed only in about one of the three subjects with hypertension and one of the four subjects with hyperlipidemia . The levels of blood pressure and plasma total cholesterol are important variables influencing the GP to prescribe a BPLD and /or LLD In the Study of Men Born in 1913 it was possible to investigate the influence of repeated health examinations on mortality in a prospect i ve cohort study . On January 1 , 1963 , 1010 men in the experimental grop and 1956 in the control group were alive . The experimental group took part in repeated examinations in 1963 , 1967 , 1973 and 1980 . Overt diseases were treated accordingly . Newly detected hypertension was also treated . By the end of a 15-year-long observation period , the cumulative mortality in the experimental group ( 14.5 % ) was not significantly lower than that in the control group ( 15.7 % ) . In the experimental group , 855 took part . The mortality was significantly higher in the non-participating group . The autopsy frequency decreased for in-hospital deaths but increased for deaths outside hospital during the study period BACKGROUND Timely recognition and prevention of health problems among elderly people have been shown to improve their health . In this r and omized controlled trial the authors examined the impact of preventive home visits by a nurse compared with usual care on the outcomes of frail elderly people living in the community . METHODS A screening question naire identified eligible participants ( those aged 70 years or more at risk of sudden deterioration in health ) . Those r and omly assigned to the visiting nurse group were assessed and followed up in their homes for 14 months . The primary outcome measure was the combined rate of deaths and admissions to an institution , and the secondary outcome measure the rate of health services utilization , during the 14 months ; these rates were determined through a medical chart audit by a research nurse who was blind to group allocation . RESULTS The question naire was mailed to 415 elderly people , of whom 369 ( 88.9 % ) responded . Of these , 198 ( 53.7 % ) were eligible , and 142 consented to participate and were r and omly assigned to either the visiting nurse group ( 73 ) or the usual care group ( 69 ) . The combined rate of deaths and admissions to an institution was 10.0 % in the visiting nurse group and 5.8 % in the usual care group ( p = 0.52 ) . The rate of health services utilization did not differ significantly between the 2 groups . Influenza and pneumonia vaccination rates were significantly higher in the visiting nurse group ( 90.1 % and 81.9 % ) than in the usual care group ( 53.0 % and 0 % ) ( p < 0.001 ) . INTERPRETATION The trial failed to show any effect of a visiting nurse other than vastly improved vaccination coverage BACKGROUND Khush Dil was set up in Edinburgh in 2002 to manage cardiovascular risk factors in South Asians . We assessed its impact in an in-service evaluation . METHODS Between June 2002 and July 2004 , 304 South Asians attended health visitor led screening clinics . Measurements included self-report , anthropometry , blood pressure and blood tests . A total 140 subjects attended follow-up screening ( henceforth returnees ) . The outcomes relate to them . RESULTS In most respects , including ethnicity , family history , medical history and motivational stage , returnees were similar to the non-returnees , but were a little older and were more likely to be women . Between baseline and return visits , returnees reported an increased motivational status ( those in the action stage of change increased from 12 to 28 % ) and increased physical activity ( e.g. 45 % of women reported improvement at follow-up ) . Returnees had reduced their risk factor profiles at follow-up in a range of risk factors , e.g. reduction in cholesterol ( 0.19 mmol/l ; 95 % CL , 0.1 - 0.37 ) , in diastolic and systolic blood pressures ( 3.15 and 3.7 mmHg , respectively ) and in weight ( 0.61 kg ; 95 % CL , 0.22 - 1.02 ) . CONCLUSIONS The Khush Dil Project had an impact as indicated by self-report , physical measures and laboratory tests . Such initiatives now need evaluation for cost-effectiveness . Cluster r and omized controlled trials warrant consideration A controlled trial was undertaken to evaluate the practical consequences of screening in general practice . Of 2420 people aged 40 - 64 years examined in 1967 - 68 , 191 ( 7.9 % ) had previously been told , at some time , that they had raised blood-pressure , other than during pregnancy . However , only 77 ( 3 - 2 % ) had any record of current antihypertensive treatment . Screening result ed in a further 50 persons ( 2 - 1 % ) being newly diagnosed as hypertensive in 1967 - 68 and a further 9 in 1969 - 70 . Antihypertensive treatment was given to 21 of these immediately following diagnosis , while the treatment was adjusted in 23 of those already known to be hypertensive . In 1972 - 73 the blood-pressures of the screening population were directly compared with the control group . No significant differences in the distributions of their blood-pressure levels were observed . Over 95 % of the new hypertensives discovered by the screening process in the control group in 1972 - 73 had visited their general practitioners for some reason during the previous five years . This suggests that " case-finding " by general practitioners would be more cost-effective than setting up separate blood-pressure screening clinics . However , the results of this study indicate that we need to know more about how raised blood-pressure can be successfully controlled over a long time , before any mass screening programmes can be actively encouraged BACKGROUND Research on question naires as screening tools for psychiatric disorders has yielded conflicting results . AIM To examine the effect of a routinely administered question naire on recognition of common psychiatric disorders in general practice . DESIGN OF STUDY R and omised controlled trial . SETTING Twenty-eight general practice s in Aarhus County , Denmark . METHOD Thirty-eight general practitioners ( GPs ) and 1785 consecutive patients , aged 18 - 65 years old , presenting with a new health problem , participated . Before consultation , patients were screened using a brief screening question naire ( SQ ) including somatisation , anxiety , depression , and alcohol abuse scales . Patients were r and omised to one of two groups : 900 question naires were disclosed and scored by the GPs , 885 were blinded . A stratified sub sample of 701 patients was interviewed after the consultation using a st and ardised psychiatric research interview ( SCAN ) . RESULTS Overall the GPs ' recognition rates were 14 % ( 95 % confidence interval [ CI ] = -2 to 30 ) better for depression and 35 % ( 95 % CI = 2 to 68 ) better for alcohol problems when SQs were disclosed . Recognition rates for anxiety improved 8 % ( 95 % CI = -9 to 26 ) overall . In the case of somatoform disorders , disclosure showed no effect overall . Among those with high SQ scores , however , disclosure increased recognition rates on any mental disorder evaluated . CONCLUSION This study demonstrated limited usefulness for routine screening for common psychiatric disorders . However , findings suggest that the SQ may be useful for case-finding among a subgroup of patients with high SQ scores A r and omized , controlled trial was conducted to assess the effects of a financial and office systems intervention to increase preventive care in physicians ' offices for patients aged 65 years or older . A total of 1,914 patients from 10 primary -care medical practice s in central North Carolina were r and omized within practice s to an intervention and a usual-care control group . The intervention consisted of full Medicare reimbursement to physicians for preventive care and health promotion packages ( thus making these services free for patients ) , regular prompting of physicians to routinely schedule preventive care visits , a new office system in which nurses carried out many preventive procedures , and a form for charting preventive care . The performance of screening tests dramatically increased in the intervention group relative to control ( P < 0.001 ) , but there was evidence of lack of follow-up of abnormal findings by physicians . At the 2-year follow-up , there were minimal differences between intervention and control groups in health-related quality -of-life indicators . Relative to the $ 294 per patient 3-year cost to Medicare for waivered services , the intervention was reimbursed-cost neutral or slightly cost reducing ( $ 190 over 3 years ) for Medicare . It is concluded that adding reimbursement for preventive services to Medicare — even with the office systems changes made in this study —will not by itself lead to effective implementation of preventive services in community medical practice s. To enhance patient benefit from preventive services , greater attention needs to be focused on an organized approach to patient follow-up OBJECTIVE To test the effectiveness of customized , family-oriented reminder letters in activating patients to seek appropriate preventive services . DESIGN R and omized clinical trial . One group received computer-generated , customized letters explaining recommended preventive procedures for each family member . A second group received a form letter listing recommendations for all preventive procedures for all age and sex groups . A third group ( control group ) received no letters . SETTING A private medical centre , without university affiliation , in rural Quebec . PARTICIPANTS From 8770 patients who met study criteria , 719 families were r and omly selected . Data were available for 1971 of 1998 patients in these families . MAIN OUTCOME MEASURES The Family Received Index is the proportion of all procedures for which a family was overdue that they received . The Family End-of- study Up-to- date Index is the proportion of procedures for which the family was eligible and for which they were up-to- date at the end of the study . RESULTS The Family Received Index for families mailed customized letters was more than double the index for patients not mailed letters ( Kruskal-Wallis P = .0139 ) . Comparison of the Family End-of- study Up-to- date indices also demonstrated that families of patients sent customized letters were more likely to be up-to- date than families not sent letters ( Kruskal-Wallis P = .0054 ) . No statistically significant difference appeared between the number of preventive measures received by the control group and the form-letter group . CONCLUSIONS This study demonstrates a clinical ly small but statistically significant value to customizing reminder letters OBJECTIVES To assess the effect of a team of geriatrics specialists on the practice style of primary care providers ( PCPs ) and the functioning of their patients aged 75 and older . DESIGN R and omized , controlled trial . SETTING Two primary care clinics in the Seattle , Washington , area . PARTICIPANTS Thirty-one PCPs and 874 patients aged 75 and older . INTERVENTION An interdisciplinary team of geriatrics specialists worked with patients and providers to enhance the geriatric focus of care . MEASUREMENTS Main outcomes were a practice style reflecting a geriatric orientation and patient scores on the physical and affect subscales of the Arthritis Impact Measurement Scale 2-Short Form . Secondary outcomes were hospitalizations , incident disability in activities of daily living ( ADLs ) , and PCP perceptions of the intervention . Death rates were also assessed . RESULTS Intervention providers screened significantly more for geriatric syndromes at 12 months , but this finding did not persist at 24 months . There were no significant differences in adequate hypertension control or high-risk prescribing at 12 or 24 months of follow-up . There were no significant differences in patient functioning or significant differences in hospitalization rates at either time point . Meaningful differences were observed in ADL disability at 12 but not 24 months . PCPs viewed the intervention favorably . Seventy-eight participants died over the 24 months of follow-up ; the proportion dying was higher in the intervention group ( 11.4 % in intervention group vs 7.1 % of controls , P=.03 ) . CONCLUSION The addition of an interdisciplinary geriatric team was acceptable to PCPs and had some effect on care of geriatric conditions but little effect on patient function or the use of inpatient care and was associated with greater mortality Abstract Objective : To assess the effectiveness of health checks by nurses in reducing risk factors for cardiovascular disease in patients from general practice . Design : R and omised controlled trial . Setting : Five urban general practice s in Bedfordshire . Subjects : 2136 patients receiving an initial health check in 1989 - 91 and scheduled to be re-examined one year later in 1990 - 2 ( intervention group ) ; 3988 patients receiving an initial health check in 1990 - 2 ( control group ) . All patients were aged 35 - 64 years at recruitment in 1989 . Main outcome measures : Serum total cholesterol concentration , blood pressure , body mass index , confirmed smoking cessation . Results : Mean serum total cholesterol was 2.3 % lower in the intervention group than in the controls ( difference 0.14 mmol/l ( 95 % confidence interval 0.08 to 0.20 ) ) ; the difference was greater in women ( 3.2 % , P<0.0001 ) than men ( 1.0 % , P=0.18 ) . There was no significant difference in smoking prevalence , quit rates , or body mass index . Systolic and diastolic blood pressure were 2.5 % and 2.4 % lower respectively in the intervention group . The proportion of patients with diastolic blood pressure > = 100 mm Hg was 2.6 % ( 55/2131 ) in the intervention group and 3.4 % ( 137/3987 ) in the controls ( difference 0.9 % ( 0.0 to 1.7 ) ; the proportion with total cholesterol concentration > = 8 mmol/l 4.8 % ( 100/2068 ) and 7.6 % ( 295/3905 ) ( difference 2.7 % ( 1.5 to 4.0 ) ) ; and that with body mass index > = 30 12.4 % ( 264/2125 ) and 14.0 % ( 559/3984 ) ( difference 1.6 % ( -0.2 to 3.4 ) ) . Conclusion : General health checks by nurses are ineffective in helping smokers to stop smoking , but they help patients to modify their diet and total cholesterol concentration . The public health importance of this dietary change depends on whether it is sustained Abstract A preventive trial aim ing at treatment of the risk factors hypertension , raised serum cholesterol , smoking , and , to some degree , low physical activity is described . The study population comprises all men in the city born in 1915–1925 ; around 30,000 men . They were r and omly divided into one treatment group and two control groups . A follow-up examination 4 years after the first examination is planned . The endpoints are deaths , all causes and cause-specific ; nonfatal myocardial infa rct ion ; and nonfatal stroke , and these are continuously followed by special registers . Some cross-sectional results from three age groups , hitherto examined , are given . The problems of making people aware of their health problems and treatment of risk factors in a community are discussed The purpose of this study was to test the hypothesis that there is a positive association between physical and psychiatric disorder . The study was design ed to reduce potential sources of bias and the approach included r and om sampling of a general practice population ; independent assessment s of the physical and psychiatric states using objective methods and strict criteria for diagnosis ; and the use of a control group . The results suggest that the hypothesis is confirmed and furthermore that ‘ clustering ’ of both types of disorder occurred in some individuals BACKGROUND Evaluation of health care contacts from first events alone often misses large amounts of potentially important data and may produce different results than evaluation of all data including recurrent events . OBJECTIVE We aim to bring the different method ological approaches for analysing longitudinal health care data to the attention of research ers in primary care . METHODS We used hospital admission data from the Ebeltoft Health Promotion Project , a r and omized trial in primary care examining the effect of preventive health checks . Comparisons included three r and omized groups : an intervention group receiving health checks , a group where intervention consisted of a health check followed by a health discussion with the GP and one control group . RESULTS Both intervention groups had approximately 20 % fewer hospital admissions than the control group over a 6 year period . If dependence among recurrent events is excluded , such a reduction amounts to a highly significant effect . Use of the st and ard Poisson distribution for analysing recurrent events and exclusion of their dependent structure causes data interpretation to be incorrect , because the model does not account for the extra variability between persons ; the result ing 95 % CIs would therefore be too small . CONCLUSION Analysis of health care contacts should embrace both first and recurrent events and it should use a model appropriate to these data . An individual rate model that includes a parameter of an unspecified individual event distribution frailty may be a natural choice when analysing longitudinal data of contacts to the health care system in broad terms Methods This study is an economic evaluation alongside a pragmatic , multi-worksite , r and omized trial comparing enhanced usual care ( EUC ; usual care plus biometric screening ) to the addition of a naturopathic approach to CVD prevention ( NC+EUC ; an individualized package of lifestyle counseling and nutritional medicine ) . Biometric and self-report outcomes were collected at 0 , 6 , and 12 months . Cost-effectiveness is determined from the societal and employer perspectives for participants who consented ( before r and omization ) to make available their electronic employer sick leave and medical cl aims data OBJECTIVE To study the feasibility of a cardiovascular prevention programme . DESIGN Opportunistic screening for cardiovascular risk factors . Advice and treatment to reduce identified cardiovascular risk factors . Individually design ed follow-up . SETTING Primary health care in Sollentuna ( 51,000 inhabitants ) , Sweden . SUBJECTS Visitors to health care centres . MAIN OUTCOME MEASURES Feasibility and effectiveness to reduce identified cardiovascular risk factors . RESULTS During 4 years 5622 persons , of whom 4655 ( 83 % ) were in the age group 20 - 60 years , participated in the programme . The prevalences of risk factors as smoking , overweight , hypertension , hypercholesterolaemia and hypertriglyceridaemia were high . At follow-up investigations , mean S-cholesterol levels were reduced by 7 % among men and 10 % among women . S-triglycerides were reduced by 24 % and 42 % , respectively . Diastolic blood pressures were reduced in men from 95 to 90 mmHg and in women from 94 to 88 mmHg . However , no effects on weight were noted and due to a low follow-up rate meaningful analysis of smoking habits was not possible . CONCLUSION A programme for cardiovascular screening and prevention can be integrated in the primary health care system . Prevalent cardiovascular risk factors like hypercholesterolaemia , hypertriglyceridaemia and high blood pressure were significantly reduced after intervention BACKGROUND In-home preventive visits with multidimensional geriatric assessment s can delay the onset of disabilities in older people . METHODS This was a stratified r and omized trial . There were 791 participants , community-dwelling people in Bern , Switzerl and , older than 75 years . The participants ' risk status was based on 6 baseline predictors of functional deterioration . The intervention consisted of annual multidimensional assessment s and quarterly follow-up in-home visits by 3 public health nurses ( nurses A , B , and C ) , who , in collaboration with geriatricians , evaluated problems , gave recommendations , facilitated adherence with recommendations , and provided health education . Each nurse was responsible for conducting the home visits in 1 ZIP code area . RESULTS After 3 years , surviving participants at low baseline risk in the intervention group were less dependent in instrumental activities of daily living ( ADL ) compared with controls ( odds ratio , 0.6 ; 95 % confidence interval , 0.3 - 1.0 ; P = .04 ) . Among subjects at high baseline risk , there were no favorable intervention effects on ADL and an unfavorable increase in nursing home admissions ( P= .02 ) . Despite the similar health status of subjects , nurse C identified fewer problems in the subjects who were visited compared with those assessed by nurses A and B. Subgroup analysis revealed that among low-risk subjects visited by nurses A and B , the intervention had favorable effects on instrumental ADL ( P = .005 ) and basic ADL ( P = .009 ) , reduced nursing home admissions ( P = .004 ) , and result ed in net cost savings in the third year ( US $ 1403 per person per year ) . Among low-risk subjects visited by nurse C , the intervention had no favorable effects . CONCLUSIONS These data suggest that this intervention can reduce disabilities among elderly people at low risk but not among those at high risk for functional impairment , and that these effects are likely related to the home visitor 's performance in conducting the visits Abstract This paper describes a control trial to evaluate the effect of screening on a middle aged general practice population . Individuals aged between 40–64 years registered with two London group practice s were included in the study . Half were r and omly allocated to the intervention or screening group ; the rest acted as controls . The study consists of three phases : 1 . 1 . Multiphasic screening offered to the screening group at two yearly intervals . 2 . 2 . A 5-year longitudinal survey of health service usage and sickness absence in both screened and control groups . 3 . 3 . A terminal survey , at the end of the 5 years , of both groups measuring the distribution of physical and socio-economic variables , the prevalence of certain symptoms and diseases , and of disability . It is hoped by these means to measure 1 . 1 . The effect of screening on physical state , anxiety about health and disability ; 2 . 2 . The short- and long-term dem and on health services re sources which result from screening ; 3 . 3 . The demographic characteristics and health status of those individuals who persistently refuse screening ; 4 . 4 . The yield of previously unknown disease . Some of the problems involved are discussed . No results are given in this paper but will be reported later A clinical controlled trial was design ed to determine the impact of Automated Multiphasic Health Testing on morbidity and attitudes . Three strata comprising 574 families ( lower-income group enrolled in health maintenance organization , lower-income not enrolled in such a project , and a middle-income group employed by a utility company ) were interviewed to obtain information on utilization , morbidity , health status , and attitudes . Sixty percent of adults in each stratum were then screened . All families were interviewed again one year later . The only significant difference found between screened and non-screened subjects was an increase in nights hospitalized for screened subjects . Physicians were interviewed to determine what abnormalities were found and what treatment was required for project and privately referred patients of these physicians . Previously unknown abnormalities prompted retesting for confirmation in only 28 per cent of the cases and even less often led to treatment Within a community-wide heart disease prevention effort , it was hypothesized that personalized risk factor screening and education would result in modified health behaviors and reduced risk factor levels for coronary heart disease . Adults from a population sample were r and omized to a community-wide screening and education program or were excluded from that program for 1 year . At the end of that year , both groups were measured for risk factor levels and related health behaviors . Those who received the screening and education program had significantly lower risk factor levels and other evidence of health behavior change , including lower blood cholesterol ( 206.9 vs 211.5 mg/dl ) , lower diastolic blood pressure ( 68.7 vs 70.0 mm Hg ) , lower resting heart rate ( 71.4 vs 72.7 bpm ) , and increased selection of low-fat and low-sodium meals in local restaurants . These data suggest that systematic risk factor screening and education may result in lower population risk for coronary heart disease |
712 | 31,235,706 | Our meta- analysis preliminarily indicates that MS treatment is an effective therapeutic modality for patients with UI . | Magnetic stimulation ( MS ) is a novel approach for treating urinary incontinence ( UI ) , but its applicability remains unclear .
This systematic review and meta- analysis were conducted to evaluate the effects of MS treatment on UI . | Introduction and hypothesisWe evaluated patients ’ perception and satisfaction with nonsurgical pulsed magnetic stimulation ( PMS ) for treatment of female stress urinary incontinence ( SUI ) in a r and omized , double-blind , sham-controlled trial . Methods Women with SUI ( n = 120 ) were r and omized to either active or sham PMS for 8 weeks ( twice/week ) . Patients answered seven questions on their perception and acceptability , each measured on a 5-point Likert scale . Treatment satisfaction was assessed using two parameters : ( i ) the single-item question “ Overall , please rate how satisfied you are with the treatment ” and ( ii ) Patient Global Impression of Improvement ( PGI-I ) . All adverse events were documented . Results A total of 115 patients completed treatments ( active : n = 57 , sham : n = 58 ) . There were no significant differences between groups in all parameters regarding perception and acceptability ( p > 0.05 ) . In terms of treatment satisfaction , a significantly higher proportion of patients in the active group ( n = 47/57 , 82.4 % ) were either mostly or completely satisfied compared with those in the sham group ( n = 27/58 , 46.6 % ) ( ( p = 0.001 ) . Similarly , a statistically significantly higher percentage of patients in the active group ( n = 39/57 , 68.4 % ) felt much or very much better compared with patients in the sham group ( n = 11/58 , 19.0 % ) as measured using the PGI-I ( p < 0.001 ) . Three ( 5.3 % ) patients in the active group and five ( 8.6 % ) in the sham group experienced adverse events ( p = 0.72 ) . Regardless of treatment arms , 109 ( 94.8 % ) patients would not consider surgical options even if they required further treatment for their condition . Conclusion PMS was well accepted , well tolerated , and result ed in a high treatment satisfaction among women with SUI Purpose : The cough stress test is a common and accepted tool to evaluate stress urinary incontinence but there is no agreement on how the test should be performed . We assessed the diagnostic ability of different cough stress tests performed when varying patient position and bladder volume using urodynamic stress urinary incontinence as the gold st and ard . The 24‐hour pad test was also evaluated . Material s and Methods : We recruited women who presented to specialty outpatient clinics with the complaint of urinary incontinence and who were recommended to undergo urodynamic testing . A total of 140 patients were r and omized to 4 cough stress test groups , including group 1—a comfortably full bladder , group 2—an empty bladder , group 3— a bladder infused with 200 cc saline and group 4—a bladder filled to half functional capacity . The sequence of st and ing and sitting was r and omly assigned . The groups were compared by 1‐way ANOVA or the generalized Fisher exact test . The & kgr ; statistic was used to evaluate agreement between the sitting and st and ing positions . The 95 % CIs of sensitivity and specificity were calculated using the Wilson method . ROC analysis was done to evaluate the performance of the 24‐hour pad test . Results : The cough stress test performed with a bladder filled to half functional capacity was the best performing test with 83 % sensitivity and 90 % specificity . There was no statistically significant evidence that the sensitivity or specificity of 1 cough stress test differed from that of the others . The pad test had no significant predictive ability to diagnose urodynamic stress urinary incontinence ( AUC 0.60 , p = 0.08 ) . Conclusions : Cough stress tests were accurate to diagnose urodynamic stress urinary incontinence . The 24‐hour pad test was not predictive of urodynamic stress urinary incontinence and not helpful when used in conjunction with the cough stress test Introduction and hypothesisWe evaluated the effects of pulsed magnetic stimulation ( PMS ) on overall and different aspects of quality of life ( QoL ) in female patients with stress urinary incontinence ( SUI ) . Methods This study involved 120 female SUI subjects aged ≥21 years old r and omized to either active or sham PMS . Treatment involved two PMS sessions per week for 2 months ( 16 sessions ) . After 2 months , subjects could opt for 16 additional sessions regardless of initial r and omization . The primary response criterion was a 7-point reduction in the total score of the International Consultation on Incontinence Question naire-Lower Urinary Tract Symptoms Quality of Life ( ICIQ-LUTSqol ) question naire . Follow-ups were conducted at months 1 , 2 , 5 , 8 , and 14 . Results At 2 months , 35 out of 60 ( 58 % ) subjects in the active arm and 21 out of 60 ( 21 % ) in the sham arm were treatment responders ( ≥7-point reduction ) ( p = 0.006 ) . There was a significant difference in changes in the mean ± SE ICIQ-LUTSqol total score between the active and sham arms ( Mdiff = −8.74 ± 1.25 vs −4.10 ± 1.08 , p = 0.006 ) . At 1-year post-treatment , regardless of number of PMS sessions ( 16 or 32 sessions ) , subjects who received active PMS ( 63 out of 94 , 67 % ) were more likely to be treatment responders compared with subjects who did not receive any active PMS ( 3 out of 12 , 25 % ; p < 0.001 ) . The impact of PMS treatment was the greatest on the “ physical activities ” domain . Conclusions PMS result ed in significant short- and long-term improvements in overall and various physical , social , and psychological aspects of AIMS To evaluate the effect of functional continuous magnetic stimulation ( FCMS ) on urgency incontinence in r and omized , sham-controlled manner . METHODS Thirty-nine patients with urgency incontinence , 16 males and 23 females ( aged 66.0 + /- 16.5 years ) , who were refractory to pelvic floor muscle training ( PFMT ) , were r and omly assigned either to the treatment schedule performing 10-week active treatment , followed by 4-week non-treatment interval and then by 10-week sham treatment ( A-S , n = 20 ) or to that performing the sham treatment first followed by 10-week active treatment ( S-A , n = 19 ) . RESULTS At 10 weeks , the number of leaks/week , the total score of the International Consultation on Incontinence- Question naire : Short Form ( ICIQ-SF ) , and maximum cystometric capacity ( MCC ) were significantly improved as compared with the initial levels ( P < 0.001 , P < 0.001 , and P = 0.003 , respectively ) in the former group , but not in the latter group . Four ( 20.0 % ) patients were cured in the A-S group , while no patient was cured in the S-A group . At the end of the A-S schedule ( 24 weeks of study ) , the effect of the active treatment was still maintained at a significantly improved level , as compared with the initial level . At the end of the S-A schedule , the number of leaks/week was significantly improved as compared with the initial level and with its 10-week level ( P < 0.001 and P = 0.049 , respectively ) , as well as ICIQ-SF total score ( P = 0.001 and P = 0.006 , respectively ) . MCC significantly increased from its initial level ( P = 0.030 ) . CONCLUSION Magnetic stimulation was effective on urgency incontinence in comparison to sham stimulation in this small patient group Purpose : Despite significant differences in success rates between surgical and nonsurgical treatments for female stress urinary incontinence , a few cross‐sectional surveys showed that most patients still prefer the latter . We evaluated the efficacy of the under studied nonsurgical treatment using pulsed magnetic stimulation for female stress urinary incontinence . Material s and Methods : This r and omized , double‐blind , sham controlled study was performed in 120 female subjects at least 21 years old with stress urinary incontinence . Treatment involved pulsed magnetic stimulation for 2 sessions per week for 2 months ( 16 sessions ) . After 2 months , subjects could opt for 16 additional sessions regardless of initial r and omization . The primary response criterion was a 5‐point reduction in the ICIQ‐UI SF ( International Consultation on Incontinence Question naire for Urinary Incontinence‐Short Form ) score . Key secondary response criteria included objective and subjective cure , supplemented by other secondary criteria . Followups were performed at months 1 , 2 , 5 , 8 and 14 . Results : At 2 months 45 of 60 subjects ( 75 % ) in the active arm vs 13 of 60 ( 21.7 % ) in the sham arm were treatment responders ( p < 0.001 ) . After 2 months 24 subjects ( 40 % ) in the active arm and 41 ( 68 % ) in the sham arm elected additional active pulsed magnetic stimulation . At 14 months , subjects who received 32 sessions of active pulsed magnetic stimulation had the highest percentage of treatment responders ( 18 of 24 or 75.0 % ) , followed by those who received 16 sessions ( 26 of 36 or 72.2 % and 28 of 41 or 68.3 % ) and those who did not receive any active pulsed magnetic stimulation ( 4 of 19 or 21.1 % ) ( p < 0.001 ) . Conclusions : The encouraging long‐term response rates show that pulsed magnetic stimulation is an attractive nonsurgical alternative for patients who do not want to undergo surgery OBJECTIVES To evaluate the efficacy and safety of magnetic stimulation for the treatment of urinary incontinence in women with overactive bladder . METHODS A total of 151 women with urgency incontinence were r and omized to the active stimulation group or the sham stimulation group in a 2:1 order . An armchair type magnetic stimulator was used for 25-min magnetic stimulation twice a week , with the maximum magnetic flux density of 560 mT peak at 10 Hz . The sham device was set to deliver in a 5-s " on"-5-s " off " pulsing manner with the maximum intensity of 20.4 % of active stimulation at 1 Hz . The study consisted of a baseline period for 1 week , and a treatment period for 6 weeks . The primary end-point was the number of leaks/week from the bladder diary . The secondary end-points were the number of voids and urgency/24 h , mean and maximum voided volume , and the quality of life assessment . RESULTS Changes from baseline in the active and sham group , respectively , were -13.08 ± 11.00 and -8.68 ± 13.49 in leaks/week ( P = 0.038 ) , -2.65 ± 2.52 and -1.53 ± 2.39 in number of urgency/24 h ( P = 0.011 ) , and 14.03 ± 34.53 mL and -4.15 ± 40.60 mL in mean voided volume ( P = 0.0056 ) . As for safety , except for diarrhea and constipation , no patients experienced any device-related adverse event . CONCLUSIONS Magnetic stimulation is effective for the treatment of urgency incontinence in female patients with overactive bladder Background There is currently a lack of r and omized , sham-controlled trials that are adequately powered , using vali date d outcomes , to allow for firm recommendations on the use of magnetic stimulation for stress urinary incontinence . We report a protocol of a multicenter , r and omized , double-blind , sham-controlled parallel-group trial to evaluate the efficacy of magnetic stimulation for stress urinary incontinence . Methods / Design One hundred twenty subjects with stress urinary incontinence will be r and omized in a 1:1 allocation to either active or sham magnetic stimulation using computer-generated , permuted blocks of variable sizes . Subjects will receive 2 sessions of magnetic stimulation per week for 8 weeks ( 16 sessions total ) . The primary outcome is the improvement in severity of involuntary urine loss based on the International Consultation on Incontinence Question naire for Urinary Incontinence Short Form at the end of treatment sessions compared with baseline . Secondary outcomes include cure , stress urinary incontinence – related symptoms ( incontinence episode frequency , urine loss in 1-hour pad test , pelvic floor muscle strength ) and health-related quality of life ( Patient Global Impression of Improvement , International Consultation on Incontinence Question naire – Lower Urinary Tract Symptoms Quality of Life and EQ-5D ) . The safety of magnetic stimulation will also be assessed . Besides evaluation of clinical treatment effectiveness , cost-effectiveness analysis using patient-reported outcomes will be performed . Discussion This trial is design ed to provide pending outcome information on this non-invasive treatment option . We intend to acknowledge the existing flaws in previous clinical trials and determine conclusively whether magnetic stimulation is effective for stress urinary incontinence . Trial registration Clinical Trials.gov Identifier : NCT01924728 . Date of Registration : 14 August 2013 PURPOSE We design ed an investigational study and placebo controlled trial to evaluate the potential efficacy of magnetic stimulation of the sacral roots for the treatment of stress incontinence . MATERIAL S AND METHODS A total of 75 patients with stress incontinence were studied . A 15 Hz . repetitive magnetic stimulation of the sacral roots with 50 % intensity output and duration of 5 seconds per minute was applied for 30 minutes . Urodynamic investigations under magnetic stimulation were performed in 13 patients to evaluate acute effects to lower urinary tract function . There were 62 women ( mean age 58 years ) enrolled in a placebo controlled study to investigate the short-term efficacy of magnetic stimulation . The number of leaks for 3 days , amount of urine loss on a pad test and quality of life score were evaluated before and 1 week after stimulation . RESULTS The urodynamic investigations revealed an apparent elevation of urethral closure pressure induced by stimulation ( mean 8.2 + /- 3.0 cm H2O , p = 0.0000004 ) and a significant increase in bladder capacity after stimulation ( mean 40.0 + /- 51.0 ml . , p = 0.0152 ) . In the placebo controlled study the number of leaks and amount of urine loss on a pad test significantly decreased more in the active than in the sham stimulation group ( p = 0.0023 and 0.0377 , respectively ) . The quality of life score significantly improved in the active stimulation group ( p = 0.0006 ) in contrast to no significant improvement in the sham stimulation group . The improvement rate in the active stimulation group was 74 % , which was significantly higher than the 32 % in the sham stimulation group ( p = 0.0009 ) . No adverse effects were noted in any patients . CONCLUSIONS These results suggest that magnetic stimulation of the sacral roots may be useful for the treatment of stress incontinence . Further studies are needed to evaluate the long-term efficacy of this potential treatment OBJECTIVE : To estimate costs for incontinence management , health-related quality of life , and willingness to pay for incontinence improvement in women electing surgery for stress urinary incontinence . METHODS : A total of 655 incontinent women enrolled in the Stress Incontinence Surgical Treatment Efficacy Trial , a r and omized surgical trial . Baseline out-of-pocket costs for incontinence management were calculated by multiplying self-report of re sources used ( supplies , laundry , dry cleaning ) by national re source costs ( $ 2006 ) . Health-related quality of life was estimated with the Health Utilities Index Mark 3 . Participants estimated willingness to pay for 100 % improvement in incontinence . Potential predictors of these outcomes were examined by using multivariable linear regression . RESULTS : Mean age was 52±10 years , and mean number of weekly incontinence episodes was 22±21 . Mean and median ( 25 % , 75 % interquartile range ) estimated personal costs for incontinence management among all women were $ 14±$24 and $ 8 ( interquartile range $ 3 , $ 18 ) per week , and 617 ( 94 % ) women reported any cost . Costs increased significantly with incontinence frequency and mixed compared with stress incontinence . The mean and median Health Utilities Index Mark 3 scores were 0.73±0.25 and 0.84 ( interquartile range 0.63 , 0.92 ) . Women were willing to pay a mean of $ 118±$132 per month for complete resolution of incontinence , and willingness to pay increased significantly with greater expected incontinence improvement , household income , and incontinent episode frequency . CONCLUSION : Urinary incontinence is associated with substantial costs . Women spent nearly $ 750 per year out of pocket for incontinence management , had a significant decrement in quality of life , and were willing to pay nearly $ 1,400 per year for cure . LEVEL OF EVIDENCE : AIM The aim of this study was to investigate the short and long-term effects of repetitive magnetic stimulation on the sacral roots in a homogeneous group of patients affected by stress incontinence . METHODS Twenty women with urinary stress incontinence were r and omly assigned to an active or a sham stimulation group . Fifteen-Hz repetitive magnetic stimulation of the sacral roots ( S2-S4 ) was applied for 15 min . Patients were treated with magnetic stimulation for 3 days a week for 2 weeks ( 6 times in all ) . The clinical outcome was assessed before ( T1 ) and 1 week ( T2 ) and 1 month ( T3 ) after stimulation . Main outcome measures were : the King 's Health Question naire , the SEAPI-QMM scale and the amount of urinary loss in a 1-h pad test and stress test . RESULTS At T2 patients in the active stimulation group showed improvement in health perception ( P<0.001 ) , social limitation ( P<0.01 ) , sleep/energy performance ( P<0.05 ) and severity measure score ( P<0.05 ) not observed in the sham stimulation group ; a significant decrease in SEAPI-QMM score was noted only in the active group at T2 ( P<0.05 ) . These results were no longer observed at T3 . We also observed a decrease in the amount of urine loss quantified with the pad test and stress test in the active stimulation group . CONCLUSION Repetitive magnetic stimulation of the sacral roots has a short-term effect on some aspects of the quality of life of the patients , but it did not prove effective using quantified measurement PURPOSE In this study we determined the efficacy of functional magnetic stimulation ( FMS ) compared to placebo for treating women with mixed urinary incontinence ( MUI ) . MATERIAL S AND METHODS A total of 39 women with MUI were r and omly assigned to the FMS group ( 23 patients ) or to the placebo group ( 16 patients ) . FMS was applied continuously at 18.5 Hz day and night for 2 months . Conventional urodynamic studies were performed before and after stimulation . Outcome measures assessed were clinical ( daytime frequency , nocturia , pad use , pad weight ) and urodynamic variables ( first sensation of bladder filling , maximum cystometric capacity , maximum urethral closure pressure ) , and patient subjective assessment ( visual analogue scale ) . RESULTS After 2 months of FMS significant decreases in voiding frequency ( from 9.0 to 6.7 , p = 0.0002 ) , nocturia ( from 2.6 to 1.4 , p = 0.0007 ) and pad use ( from 3.9 to 2.2 , p = 0.007 ) were observed only in the FMS group . First sensation of bladder filling and maximum cystometric capacity increased significantly after stimulation compared with prestimulation levels only in the FMS group , p = 0.003 ( from 118 to 174 ml ) and p = 0.00004 ( from 267 to 396 ml ) , respectively . A total of 18 women ( 78.3 % ) reported an improvement in symptoms after FMS with an average success rate of 41.9 % . The success rate was significantly lower in the placebo group ( p = 0.021 ) at 22.9 % . CONCLUSIONS Functional magnetic stimulation was useful and safe for treating women with MUI OBJECTIVES To report the first data from a prospect i ve clinical study to determine the feasibility of using extracorporeal magnetic innervation ( ExMI ) for the treatment of stress urinary incontinence . METHODS We studied 83 women with demonstrable stress urinary incontinence . Treatments were for 20 minutes , twice a week for 6 weeks . For treatment , the patient sits fully clothed on a special chair ; within the seat is a magnetic field generator that produces the rapidly changing magnetic field flux . Objective measures included bladder diaries , dynamic pad weight testing , urodynamic studies , and quality of life survey . RESULTS Fifty patients have been followed up for longer than 3 months ( 33 patients for less than 3 months ) ; 17 patients ( 34 % ) were dry , 16 ( 32 % ) were using not more than 1 pad per day , and 17 ( 34 % ) were using more than 1 pad per day . Pad use was reduced from 2.5 to 1.3 ( P = 0.001 ) and leak episodes per day were reduced from 3.3 to 1.7 ( P = 0.001 ) . The pad weight was reduced from 20 to 15 g. Detrusor instability was found in 5 patients before but was demonstrated in only 1 patient after treatment . CONCLUSIONS ExMI therapy offers a new effective modality for pelvic floor muscle stimulation . ExMI is painless , there is no need for a probe , and no need to undress for treatments . Longer follow-up is required to determine how long the benefits of treatment last and whether retreatment will be necessary OBJECTIVE Estimate the prevalence of urinary incontinence ( UI ) , overactive bladder ( OAB ) , and other lower urinary tract symptoms ( LUTS ) among men and women in five countries using the 2002 International Continence Society ( ICS ) definitions . METHODS This population -based , cross-sectional survey was conducted between April and December 2005 in Canada , Germany , Italy , Sweden , and the United Kingdom using computer-assisted telephone interviews . A r and om sample of men and women aged > /= 18 yr residing in the five countries and who were representative of the general population s in these countries was selected . Using 2002 ICS definitions , the prevalence estimates of storage , voiding , and postmicturition LUTS were calculated . Data were stratified by country , age cohort , and gender . RESULTS A total of 19,165 individuals agreed to participate ; 64.3 % reported at least one LUTS . Nocturia was the most prevalent LUTS ( men , 48.6 % ; women , 54.5 % ) . The prevalence of storage LUTS ( men , 51.3 % ; women , 59.2 % ) was greater than that for voiding ( men , 25.7 % ; women , 19.5 % ) and postmicturition ( men , 16.9 % ; women , 14.2 % ) symptoms combined . The overall prevalence of OAB was 11.8 % ; rates were similar in men and women and increased with age . OAB was more prevalent than all types of UI combined ( 9.4 % ) . CONCLUSIONS The EPIC study is the largest population -based survey to assess prevalence rates of OAB , UI , and other LUTS in five countries . To date , this is the first study to evaluate these symptoms simultaneously using the 2002 ICS definitions . The results indicate that these symptoms are highly prevalent in the countries surveyed PURPOSE We design ed an investigational study and placebo controlled trial to evaluate the efficacy of magnetic stimulation of the sacral roots for treating urinary frequency and urge incontinence . MATERIAL S AND METHODS A total of 48 women 43 to 75 years old ( mean age 61 ) with the complaint of urinary frequency and /or urge incontinence were studied . We applied 15 Hz . repetitive magnetic stimulation of the sacral roots with 50 % intensity output for 5 seconds per minute for 30 minutes . Urodynamic investigations during magnetic stimulation were performed in 11 cases to evaluate acute effects for lowering urinary tract function . Another 37 women were enrolled in a placebo controlled study to investigate short-term effects . The mean number of voids daily , mean urine volume per void , number of leaks for 3 days and quality of life score were evaluated before and 1 week after stimulation . RESULTS Urodynamic investigations revealed apparent elevation in mean maximum urethral closure pressure plus or minus st and ard deviation during stimulation in all 11 cases ( 8.4 + /- 3.6 cm . water , p = 0.00001 ) and a significant increase in mean bladder capacity after stimulation ( 58.2 + /- 50.2 ml . , p = 0.003 ) . In the placebo controlled study all parameters significantly improved in the active stimulation group . Intergroup comparison showed that mean urine volume per void , mean number of leaks and mean quality of life score improved more significantly in the active than in the sham stimulation group ( 23.5 + /- 25.6 ml . versus 6.2 + /- 22.5 , p = 0.04 , 3.6 + /- 4.1 versus 0.4 + /- 1.4 , p = 0.04 and 1.4 + /- 1.3 versus 0.4 + /- 0.8 , p = 0.01 , respectively ) . No adverse effects were noted in any patients . CONCLUSIONS These results suggest that magnetic stimulation of the sacral roots may be useful for treating urinary frequency and urge incontinence OBJECTIVES To determine the efficacy and safety of functional magnetic stimulation ( FMS ) produced by the Pulsegen device compared with placebo in the treatment of women with urinary incontinence . METHODS Fifty-five women with urinary incontinence were r and omly assigned to the active FMS group ( 30 patients ) or the placebo group ( 22 patients ) . Each patient in the active group received a Pulsegen device , which produced a pulsating magnetic field of B = 10 microT intensity and a frequency of 10 Hz . Patients were asked to wear the Pulsegen device day and night for 2 months . Clinical and urodynamic data were collected before and after FMS and analyzed using nonparametric statistics . RESULTS Compared with the placebo , the number of pads used was significantly lower ( P = 0.0031 ) after FMS , as was the pad weight ( P = 0.014 ) . In patients from the active group , a significant improvement in the power of the pelvic floor muscle contractions ( P = 0.0071 ) , as well as in the duration of the pelvic floor muscle contractions ( P = 0.038 ) , was observed . After FMS , a 56.3 % improvement in urinary incontinence symptoms was reported by patients in the active group , a significantly greater difference ( P = 0.00012 ) compared with the reported 26.3 % improvement in symptoms in the placebo group . CONCLUSIONS We believe that FMS represents a new method in the conservative treatment of urinary incontinence . Magnetic stimulation with the Pulsegen device is efficient and safe . It can be used at home and , because of its small size , wearing the device is not annoying for patients OBJECTIVE The aim of the present study was to evaluate the effect of magnetic stimulation on urodynamic stress incontinence refractory to pelvic floor muscle training in a r and omized sham-controlled study . METHODS Female patients with urodynamic stress incontinence who had not been cured by pelvic floor muscle training were r and omly assigned at a ratio of 2 : 1 to either active treatment or sham treatment for 10 weeks . The r and omization was made using magnetic cards for individuals indicating active or sham stimulation . The primary endpoint was changes in the number of incontinence episodes/week , with secondary endpoints of the degree of incontinence ( in g/day ; determined using the pad test ) , the total score on the International Consultation on Incontinence Question naire - Short Form ( ICIQ-SF ) , the ICIQ quality of life ( QOL ) score , and the abdominal leak point pressure ( ALPP ) on urodynamic study . RESULTS Although 39 patients were enrolled in the study , 9 dropped out , leaving a total patients for analysis ( 18 in the active treatment group , 12 in the sham treatment group ) . The number of incontinence episodes/week , the degree of incontinence , total ICIQ-SF score , ICIQ-QOL score , and ALPP were significantly improved after active treatment compared with baseline ( all P < .05 ) , but did not change significantly after sham treatment . There was a significant intergroup difference with regard to changes from baseline in the ICIQ-SF and ALPP in favor of the active treatment group ( P < .05 ) . There were no significant differences in any other parameters between the 2 groups . Treatment-related adverse events were not found in both groups . CONCLUSION Magnetic stimulation was effective in treating urodynamic stress incontinence BACKGROUND Female urinary incontinence ( UI ) , overactive bladder ( OAB ) , and other lower urinary tract symptoms ( LUTS ) are highly prevalent conditions with a profound influence on well-being and quality of life . There are a few studies describing progression as well as remission , in the short term , of UI in the general population as well as in selected groups ; at present , there are very few population -based studies describing the natural course of other LUTS in the same women , and there are no long-term longitudinal studies . OBJECTIVE To describe the prevalence of UI , OAB , and other LUTS in the same women studied prospect ively over time and , thus , to assess possible progression or regression . DESIGN , SETTING , AND PARTICIPANTS A longitudinal population -based study was performed in one primary health care district in the city of Gothenburg , Sweden . The participants were a sample of women aged > or = 20 yr who were r and omly selected from the Swedish National Population Register , assessed in 1991 ( n=2911 ) , and available for re assessment in 2007 ( n=1408 ) . METHODS A self-administered postal question naire regarding UI , OAB , and other LUTS was returned by 77 % of the contacted women in 1991 . The same women who responded in 1991 and who were still alive and available in the Swedish National Population Register 16 yr later were reassessed using a similar self-administered postal question naire . RESULTS AND LIMITATIONS In 2007 , 1081 of the available 1408 women responded to the question naire ( 77 % ) . The overall prevalence of UI , OAB , nocturia , and daytime micturition frequency of eight or more times per day increased by 13 % , 9 % , 20 % ( p<0.001 ) , and 3 % ( p<0.05 ) , respectively , from 1991 to 2007 . The incidence of UI and OAB were 21 % and 20 % , respectively , and the corresponding remission rates were 34 % and 43 % , respectively . Women with OAB symptoms were classified as OAB dry or OAB wet , depending on the presence or absence of concomitant UI . The prevalence of OAB dry did not differ between the two assessment occasions ( 11 % and 10 % , respectively ) , but the prevalence of OAB wet increased from 6 % to 16 % ( p<0.001 ) . CONCLUSIONS UI and other LUTS constitute dynamic conditions . In this study , there was a marked overall increase in the prevalence of UI , OAB , and nocturia in the same women from 1991 to 2007 . Both incidence and remission of most symptoms were considerable |
713 | 31,593,543 | This systematic review shed light on the most prominent health outcomes that can be improved using mHealth technology interventions in developing countries . | BACKGROUND The use of mobile health ( mHealth ) technologies to improve population -level health outcomes around the world has surged in the last decade .
Research supports the use of mHealth apps to improve health outcomes such as maternal and infant mortality , treatment adherence , immunization rates , and prevention of communicable diseases .
However , developing countries face significant barriers to successfully implement , sustain , and exp and mHealth initiatives to improve the health of vulnerable population s. OBJECTIVE We aim ed to identify and synthesize barriers to the use of mHealth technologies such as text messaging ( short message service [ SMS ] ) , calls , and apps to change and , where possible , improve the health behaviors and health outcomes of population s in developing countries . | AIMS AND OBJECTIVES To compare drug adherence to lipid-lowering therapy among out patients with coronary artery disease who received information via short message service , via short message service and Micro Letter , or via phone only . BACKGROUND Messaging applications and short message service are commonly used internationally . However , little is known about how coronary artery disease out patients in China may benefit from receiving health education through these technologies . DESIGN R and om sampling method . METHODS Data were collected from March-December 2013 . Subjects from Chengdu City , China , were r and omised to three groups : short message service , short message service + Micro Letter , and phone ( control ) . Appointment reminders and health information were delivered to patients in accordance with design ations . After six months , adherence to statin prescriptions was compared among the groups by using the Morisky Medication Adherence Scale . Logistic regression analysis was applied to determine those independent variables that were related to adherence . RESULTS The short message service and short message service + Micro Letter groups had better cumulative adherence ( lower Morisky Medication Adherence Scale scores ) after six months than phone group , and the short message service + Micro Letter group had better cumulative adherence ( lower Morisky Medication Adherence Scale scores ) than the short message service group . Female sex , older age and marriage show positive associations with adherence . CONCLUSIONS Short message service and messaging applications , such as Micro Letter , are effective means of providing discharged patients with reminders and coronary artery disease-related health information . Implementation of a short message service + Micro Letter program can improve outpatient adherence to medication . RELEVANCE TO CLINICAL PRACTICE This research offers useful information to help medical staff design effective interventions to improve medication compliance among coronary artery disease patients AIM Short message service ( SMS ) is an applied technology of communication that enables the transfer of information and can be used as a part of medical efforts to motivate clients to improve their behavior regarding drug consumption . This study attempts to observe the differences in patients ' behavior as a result of either using SMS to motivate their drug consumption or by using only health providers and outreach workers to monitor them . METHODS This study used a post-test-only controlled-group design with a simple r and om sampling technique and was held in Malang , Indonesia . The sample in this study consisted of 45 patients with tuberculosis ( TB ) who received motivating SMS messages and 45 patients with only health providers and outreach workers to monitor them . RESULTS Fisher 's Exact test using a 95 % confidence interval showed that the result of this study had a P-value of 0.059 , which means that there was no difference in compliance with drug consumption between the patients who received SMS messages and the patients who were under the supervision of health providers and outreach workers . CONCLUSION It is highly recommended that the application of SMS be included in TB treatment and the evaluation of patients as an alternative method of controlling patients ' compliance with consuming anti-TB drugs at home Background Applying mobile phones in healthcare is increasingly prioritized to strengthen healthcare systems . Antenatal care has the potential to reduce maternal morbidity and improve newborns ’ survival but this benefit may not be realized in sub-Saharan Africa where the attendance and quality of care is declining . We evaluated the association between a mobile phone intervention and antenatal care in a re source -limited setting . We aim ed to assess antenatal care in a comprehensive way taking into consideration utilisation of antenatal care as well as content and timing of interventions during pregnancy . Methods This study was an open label pragmatic cluster-r and omised controlled trial with primary healthcare facilities in Zanzibar as the unit of r and omisation . 2550 pregnant women ( 1311 interventions and 1239 controls ) who attended antenatal care at selected primary healthcare facilities were included at their first antenatal care visit and followed until 42 days after delivery . 24 primary health care facilities in six districts were r and omized to either mobile phone intervention or st and ard care . The intervention consisted of a mobile phone text-message and voucher component . Primary outcome measure was four or more antenatal care visits during pregnancy . Secondary outcome measures were tetanus vaccination , preventive treatment for malaria , gestational age at last antenatal care visit , and antepartum referral . Results The mobile phone intervention was associated with an increase in antenatal care attendance . In the intervention group 44 % of the women received four or more antenatal care visits versus 31 % in the control group ( OR , 2.39 ; 95 % CI , 1.03 - 5.55 ) . There was a trend towards improved timing and quality of antenatal care services across all secondary outcome measures although not statistically significant . Conclusions The wired mothers ’ mobile phone intervention significantly increased the proportion of women receiving the recommended four antenatal care visits during pregnancy and there was a trend towards improved quality of care with more women receiving preventive health services , more women attending antenatal care late in pregnancy and more women with antepartum complications identified and referred . Mobile phone applications may contribute towards improved maternal and newborn health and should be considered by policy makers in re source -limited setting s . Trial registration Clinical Trials.gov , NCT01821222 PURPOSE The current malaria treatment in Zambia is more than 97 % effective when the regimen is strictly adhered to . However , the mean adherence rate in sub-Saharan Africa is only 38 % to 48 % . Poor pharmacoadherence remains a significant barrier to malaria control and elimination . The purpose of this study was to determine if adherence rates to a six-dose artemesinin-based combination therapy ( ACT ) treatment differ between patients who received short message service ( SMS ) reminders and those who did not . This is the first study of its kind using SMS directly to the patient for ACT adherence in sub-Saharan Africa . DESIGN An experimental , r and omized controlled trial was conducted through a sample of 96 adult malaria patients at Fisenge Clinic in Zambia in 2014 . METHODS The intervention group received SMS messages to remind them to take their medication according to the prescribed regimen . An electronic pillbox was used to measure pharmacoadherence for both groups , and patients were classified as probably adherent or probably nonadherent . FINDINGS Data were analyzed using chi-square for association between the SMS intervention and pharmacoadherence , and logistic regression was used for predictors of adherence . No significant association was found between SMS reminders and pharmacoadherence ( χ(2 ) = 0.19 , df = 1 , p = .67 ) . Binary logistic regression indicated that there were no variables associated with adherence ( p > .05 ) . CONCLUSIONS SMS reminder messages did not appear to improve pharmacoadherence in malaria medication . CLINICAL RELEVANCE The study indicates few implication s to nursing practice due to the lack of association between SMS and adherence , but adds to current knowledge Objective To evaluate the effectiveness of daily text messages as a means to improve caregivers ’ adherence to infant micronutrient powder ( MNP ) in rural Shaanxi Province of China . Methodology 638 infants aged 6–11 months in 234 villages were involved in a cluster-r and omized controlled trial ( RCT ) . All caregivers were given free infant MNP packets at baseline in April 2013 and the follow-up survey was in July 2013 . We r and omly assigned 318 infants in 117 villages to treatment group ( receiving daily text message ) and 320 infants in the other 117 villages as control group . Results On average , daily text messages increased the number of MNP packets fed ( marginal effect = 4.63 ; 95 % confidence interval ( CI ) = 0.16 , 9.10 ) . The text message is more likely to increase the consumption of MNP packets if the primary caregiver was the mother ( marginal effect = 12.19 ; 95 % CI = 0.69 , 23.68 ) . Receiving the text message appears to significantly increase the likelihood of full adherence when the primary caregiver can either check ( odds ratio = 2.93 ; 95 % CI = 1.34 , 6.40 ) or knows how to send ( odds ratio = 3.26 ; 95 % CI = 1.53 , 6.97 ) text messages . Conclusion Daily text messages improved the consumption of infant MNP packets . However , the impact was not large enough to increase the probability of caregivers being fully adherent to the feeding instruction , which is to feed 5–7 packets per week as recommended . In addition , when the mother is the caregiver and when the caregiver can check or knows how to send text messages there is greater adherence by the primary caregivers . Trial registration http://www.is rct n.com/IS RCT AIMS AND OBJECTIVES To determine the effectiveness of an electronic messaging support service for management of cardiovascular risk factors in patients with diabetes . BACKGROUND Microletter and short message service are widely used , but their health education benefit for people with type 2 diabetes mellitus has not been investigated . DESIGN Convenience sample study with r and omised group assignment . METHODS Participants completed survey question naires , physical and laboratory evaluations between May 2015 and May 2016 and were then r and omly assigned to two groups for receipt of a microletter + short message or a phone call ( control ) . Appointment reminders and health information were sent to the intervention patients by microletter + short message . Every three months , intervention patients and control patients were followed up by telephone . After 12 months , changes in cardiovascular risk factors in each group were evaluated and compared . RESULTS There were no statistically significant changes or between-group differences in daily smoking and drinking . There were statistically significant between-group differences in glycated haemoglobin ( p = .034 ) , postpr and ial plasma glucose ( p = .001 ) , postpr and ial insulin ( p = .005 ) , total cholesterol ( p = .038 ) and low-density lipoprotein ( p < .001 ) . Levels of glycated haemoglobin ( p = .011 ) , fasting plasma glucose ( p = .007 ) , postpr and ial plasma glucose ( p < .001 ) , fasting insulin ( p = 0.004 ) , postpr and ial insulin ( p < .001 ) , total cholesterol ( p < .001 ) and low-density lipoprotein ( p < .001 ) were found to be decreased significantly in intervention patients . Systolic blood pressure decreased significantly in patients only followed by telephone ( p = .014 ) . The microletter + short message intervention was an effective means of reducing cardiovascular risk in patients with type 2 diabetes mellitus . CONCLUSION Regular smartphone communication had a favourable impact on cardiovascular risk factors in patients with type 2 diabetes mellitus . RELEVANCE TO CLINICAL PRACTICE Regular smartphone communication has a favourable impact on cardiovascular risk factors in patients with type 2 diabetes mellitus Background Large investments are currently made in community – based complementary food supplement ( Ying Yang Bao , YYB ) programs to improve nutrition of young children in rural areas in China . However , there is a lack of knowledge about the experience and challenges of implementing YYB programs in China . We aim ed to : 1 ) monitor distribution of YYB ; 2 ) assess children ’s adherence to and acceptability of YYB ; and 3 ) evaluate community – based strategies to improve the program . Methods This mixed methods evaluation study combined data from surveys and focus groups that took place during a controlled interventional evaluation trial . The trial aim ed to evaluate the effectiveness of community – based YYB distribution on improving children 's health status in rural areas in China . We conducted five cross – sectional surveys with caregivers of children aged 6–23 months ( baseline survey ( N = 1804 ) in August 2012 and four follow – up cross – sectional surveys : 1 ) N = 494 in January 2013 ; 2 ) N = 2187 in August 2013 ; 3 ) N = 504 in January 2014 ; and 4 ) N = 2186 in August 2014 ) in one rural county in Qinghai Province . We used a two – stage cluster sampling technique to select mothers with eligible children for each survey . Information was collected from caregivers on household characteristics , YYB consumption and acceptability in the surveys . High adherence in each survey was defined as children who consumed at least four YYB sachets during the previous week . A logistic regression model was developed to obtain odds ratios ( OR ) with 95 % confidence intervals of factors associated with high adherence . Also , we conducted 10 focus groups with73 caregivers and health workers involved in the YYB distribution . Content analysis was used to explore qualitative findings , which were used to gain deeper insight into the quantitative results . Results Around 90 % of caregivers had ever received YYB and more than 80 % of children ever took YYB . Caregivers mainly knew about YYB through their village doctors . High adherence to YYB increased from 49.4 % in the first follow – up survey ( January 2013 ) to 81.4 % in the last follow – up survey ( August 2014 ; P < 0.0001 ) . Repeated training sessions with village doctors could increase adherence . However , due to unplanned YYB stock – out , caregivers did not receive YYB for six months , which may have led to a decrease of high adherence from 64.1 % in the second follow – up survey ( August 2013 ) to 53.6 % in the third follow – up survey ( January 2014 ; P < 0.0001 ) . Self – reported acceptability increased from 43.2 % to 71.8 % , partly due to improving the taste of YYB , which was the main reason that children disliked taking YYB . Unfortunately , more than 60 % of caregivers did not perceive positive health improvement in their children after taking YYB . Multivariate analysis showed that children with diarrhea ( OR = 1.216 , 95 % CI 1.025–1.442 ) , cough or fever ( OR = 1.222 , 95 % CI 1.072–1.393 ) during the past two weeks had significantly lower adherence . Conclusions This evaluation study showed that program monitoring in rural West China was critically important for underst and ing program implementation and adherence trends . This led to strategic changes to the intervention over time : improving the taste of YYB ; strengthening health education of village doctors and caregivers ; and ensuring continuity of YYB supply . Future programs need to monitor program implementation in other setting s in China and elsewhere Background Mobile phone technology is utilized for better delivery of health services worldwide . In low- and -middle income countries mobile phones are now ubiquitous . Thus leveraging mHealth applications in health sector is becoming popular rapidly in these countries . To assess the effectiveness of the Continuum of Care Services ( CCS ) mHealth platform in terms of strengthening the delivery of maternal and child health ( MCH ) services in a district in Bihar , a re source -poor state in India . Methods The CommCare mHealth platform was customized to CCS as one of the innovations under a project funded by the Bill and Melinda Gates Foundation to improve the maternal and newborn health services in Bihar . The intervention was rolled out in one project district in Bihar , during July 2012 . More than 550 frontline workers out of a total of 3000 including Accredited Social Health Activists , Anganwadi Workers , Auxilliary Nurse Midwives and Lady Health Supervisors were trained to use the mHealth platform . The service delivery components namely early registration of pregnant women , three antenatal visits , tetanus toxoid immunization of the mother , iron and folic acid tablet supply , institutional delivery , postnatal home visits and early initiation of breastfeeding were used as indicators for good quality services . The result ant coverage of these services in the implementation area was compared with rest of Bihar and previous year statistics of the same area . The time lag between delivery of a service and its record capture in the maternal and child tracking system ( MCTS ) data base was computed in a r and om sample of 16,000 beneficiaries . The coverage of services among marginalized and non-marginalized castes was compared to indicate equity of service delivery . Health system strengthening was viewed from the angle of coverage , quality , equity and efficiency of services . Results The implementation blocks had higher coverage of all the eight indicator services compared to rest of Bihar and the previous year . There was equity of services across castes for all the indicators . Timely capture of data was also ensured compared to paper-based reporting . Conclusion By virtue of its impact on quality , efficiency and equity of service delivery , health care manpower efficiency and governance , the mHealth inclusion at service provision level can be one of the potential strategy to strengthen the health system Background : Folic acid supplementation is effective in reducing the risk of neural tube defects ( NTDs ) . However , the use of folic acid is low among rural women in China . Nutrition education can provide information about folic acid and encourage its use . The primary objective of this study was to test the effectiveness of a village-based nutrition intervention on folic acid use among rural women . Methods : Sixty villages were r and omly selected using multiple-stage sampling and were divided into control and intervention groups . The intervention included nutritional education at village clinics , written material s , and text messages ( SMS ) . Folic acid use knowledge and behavior was assessed at baseline and after the intervention . Results : Self-reported compliance with folic acid supplement use increased from 17.0%–29.2 % at baseline to 41.7%–59.2 % one year post-intervention . During the same period , the folic acid knowledge score in the intervention group increased from 3.07 to 3.65 , significantly higher than the control group ( 3.11 to 3.35 ) . Multivariate binary logistic regression showed that the women who received folic acid education and SMS intervention were more likely to comply with folic acid supplement recommendations . Conclusions : The results indicated that an integrated village-based folic acid education intervention may be an effective way of promoting folic acid use for the prevention of NTDs in rural women Background In Cameroon , only two-thirds of children with HIV exposure or infection receive appropriate HIV-directed medical care . Mortality , antiretroviral therapy resistance and suboptimal virological response are strongly related to missed opportunities for treatment , and , more specifically , to skipped scheduled medical appointments . The present trial , MORE CARE ( Mobile Reminders for Cameroonian Children Requiring HIV Care ) seeks to determine if reminders sent by text message ( SMS ) , phone call , or concomitant SMS and phone calls most increase the presence at medical appointments of HIV-infected or -exposed children ( efficacy ) , and which is the most efficient related to working time and financial cost ( efficiency ) . Methods / Design We will carry out a multicenter single-blind , r and omized , factorial controlled trial . A r and omization list will be electronically generated using r and om block sizes . Central allocation will be determined by sequentially numbered . A total of 224 subjects will be r and omized into four groups ( SMS , Call , SMS + Call , and Control ) with an allocation ratio of 1:1:1:1 . SMS and calls will be sent between 48 and 72 hours before the scheduled appointment . A medical assistant will send out text messages and will call participants . Our primary outcome is appointment measured by efficacy and efficiency of interventions . We hypothesize that two reminders ( concomitant use of SMS and phone calls ) as an appointment reminder is more effective to improve appointment compared to one reminder ( only SMS or only call ) , and that the most efficient is use of only SMS . The analysis will be intention to treat . Discussion This trial investigates the potential of SMS and phone calls as motivational reminders to improve children ’s adherence to medical appointments for HIV-related care in Cameroon . The intervention will act to end missed appointment due to forgetfulness . Trial registration Pan African Clinical Trials Registry : Background Effective use of proven treatments for high blood pressure , a preventable health risk , is challenging for many patients . Prompts via mobile phone SMS-text messaging may improve adherence to clinic visits and treatment , though more research is needed on impact and patient perceptions of such support interventions , especially in low-re source setting s. Method An individually-r and omised controlled trial in a primary care clinic in Cape Town ( 2012–14 ) , tested the effect of an adherence support intervention delivered via SMS-texts , on blood pressure control and adherence to medication , for hypertensive patients . ( Trial registration : Clinical Trials.gov NCT02019823 ) . We report on a qualitative evaluation that explored the trial participants ’ experiences and responses to the SMS-text messages , and identified barriers and facilitators to delivering adherence support via patients ’ own mobile phones . Two focus groups and fifteen individual interviews were conducted . We used comparative and thematic analysis approaches to identify themes and triangulated our analysis amongst three research ers . Results Most participants were comfortable with the technology of using SMS-text messages . Messages were experienced as acceptable , relevant and useful to a broad range of participants . The SMS-content , the respectful tone and the delivery ( timing of reminders and frequency ) and the relational aspect of trial participation ( feeling cared for ) were all highly valued . A subgroup who benefitted the most , were those who had been struggling with adherence due to high levels of personal stress . The intervention appeared to coincide with their readiness for change , and provided practical and emotional support for improving adherence behaviour . Change may have been facilitated through increased acknowledgement of their health status and attitudinal change towards greater self-responsibility . Complex interaction of psycho-social stressors and health service problems were reported as broader challenges to adherence behaviours . Conclusion Adherence support for treatment of raised blood pressure , delivered via SMS-text message on the patient ’s own phone , was found to be acceptable , relevant and helpful , even for those who already had their own reminder systems in place . Our findings begin to identify for whom and what core elements of the SMS-text message intervention appear to work best in a low-re source operational setting , issues that future research should explore in greater depth Background Tuberculosis is a public health problem in Cameroon , just like in many other countries in the world . The National Tuberculosis Control Programme ( PNLT ) put in place by the state , aims to fight tuberculosis through the implementation of international directives ( Directly Observed Treatment Short , DOTS ) . Despite the deployment of this strategy across the world , its implementation is difficult in the context of low-re source countries . Some expected results are not achieved . In Cameroon , the cure rate for patients with sputum positive pulmonary tuberculosis ( TPM+ ) after 6 months is only about 65 % , 20 % below the target . This is mainly due to poor patient adherence to treatment . By relying on the potential of mobile Health , the objective of this study is to evaluate the effect of SMS reminders on the cure rate of TPM + patients , measured using 6-month bacilloscopy . Methods / design This is a blinded , r and omised controlled multicentre study carried out in Cameroon . The research hypothesis is that sending daily SMS messages to remind patients to take their prescribed tuberculosis medication , together with the st and ard DOTS strategy , will increase the cure rate from 65 % ( control group : DOTS , no SMS intervention ) to 85 % ( intervention group : DOTS , with SMS intervention ) in a group of new TPM + patients . In accordance with each treatment centre , the participants will be r and omly allocated into the two groups using a computer program : the intervention group and the control group . A member of the research team will send daily SMS messages . Study data will be collected by health professionals involved in the care of patients . Data analysis will be done by the intention-to-treat method . Discussion The achieving of expected outcomes by the PNLT through implementation of DOTS requires several challenges . Although it has been demonstrated that the DOTS strategy is effective in the fight against tuberculosis , its application remains difficult in developing countries . This study explores the potential of mHealth to support DOTS strategy . It will gather new evidence on the effectiveness of mHealth-based interventions and SMS reminders in the improvement of treatment adherence and the cure rate of tuberculosis patients , especially in a low-re source country such as Cameroon . Trial registration The trial is registered on the Pan-African Clinical Trials Registry ( http://www.pactr.org ) under unique identification number : PACTR201307000583416 OBJECTIVE Hypertension and other noncommunicable diseases represent a growing threat to low/middle-income countries ( LMICs ) . Mobile health technologies may improve noncommunicable disease outcomes , but LMICs lack re sources to provide these services . We evaluated the efficacy of a cloud computing model using automated self-management calls plus home blood pressure ( BP ) monitoring as a strategy for improving systolic BPs ( SBPs ) and other outcomes of hypertensive patients in two LMICs . SUBJECTS AND METHODS This was a r and omized trial with a 6-week follow-up . Participants with high SBPs ( ≥140 mm Hg if nondiabetic and ≥130 mm Hg if diabetic ) were enrolled from clinics in Honduras and Mexico . Intervention patients received weekly automated monitoring and behavior change telephone calls sent from a server in the United States , plus a home BP monitor . At baseline , control patients received BP results , hypertension information , and usual healthcare . The primary outcome , SBP , was examined for all patients in addition to a preplanned subgroup with low literacy or high hypertension information needs . Secondary outcomes included perceived health status and medication-related problems . RESULTS Of the 200 patients recruited , 181 ( 90 % ) completed follow-up , and 117 of 181 had low literacy or high hypertension information needs . The median annual income was $ 2,900 USD , and average educational attainment was 6.5 years . At follow-up intervention patients ' SBPs decreased 4.2 mm Hg relative to controls ( 95 % confidence interval -9.1 , 0.7 ; p=0.09 ) . In the subgroup with high information needs , intervention patients ' average SBPs decreased 8.8 mm Hg ( -14.2 , -3.4 , p=0.002 ) . Compared with controls , intervention patients at follow-up reported fewer depressive symptoms ( p=0.004 ) , fewer medication problems ( p<0.0001 ) , better general health ( p<0.0001 ) , and greater satisfaction with care ( p≤0.004 ) . CONCLUSIONS Automated telephone care management plus home BP monitors can improve outcomes for hypertensive patients in LMICs . A cloud computing model within regional telecommunication centers could make these services available in areas with limited infrastructure for patient-focused informatics support We conducted a r and omized , controlled trial to test the effectiveness of a text-messaging system used for notification of disease outbreaks in Kenya . Health facilities that used the system had more timely notifications than those that did not ( 19.2 % vs. 2.6 % ) , indicating that technology can enhance disease surveillance in re source -limited setting PROBLEM Polio remains endemic in many areas of Pakistan , including large urban centres such as Karachi . APPROACH During each of seven supplementary immunization activities against polio in Karachi , mobile phone numbers of the caregivers of a r and om sample of eligible children were obtained . A computer-based system was developed to send two questions --as short message service ( SMS ) texts -- automatically to each number after the immunization activity : " Did the vaccinator visit your house ? " and " Did the enrolled child in your household receive oral polio vaccine ? " Persistent non-responders were phoned directly by an investigator . LOCAL SETTING A cluster sampling technique was used to select representative sample s of the caregivers of young children in Karachi in general and of such caregivers in three of the six " high-risk " districts of the city where polio cases were detected in 2011 . RELEVANT CHANGES In most of the supplementary immunization activities investigated , vaccine coverages estimated using the SMS system were very similar to those estimated by interviewing by phone those caregivers who never responded to the SMS messages . In the high-risk districts investigated , coverages estimated using the SMS system were also similar to those recorded -- using lot quality assurance sampling -- by the World Health Organization . LESSONS LEARNT For the monitoring of coverage in supplementary immunization activities , automated SMS-based systems appear to be an attractive and relatively inexpensive option . Further research is needed to determine if coverage data collected by SMS-based systems provide estimates that are sufficiently accurate . Such systems may be useful in other large-scale immunization campaigns OBJECTIVES To evaluate whether text-messaging programs can improve reproductive health among adolescent girls in low- and middle-income countries . METHODS We conducted a cluster-r and omized controlled trial among 756 female students aged 14 to 24 years in Accra , Ghana , in 2014 . We r and omized 38 schools to unidirectional intervention ( n = 12 ) , interactive intervention ( n = 12 ) , and control ( n = 14 ) . The unidirectional intervention sent participants text messages with reproductive health information . The interactive intervention engaged adolescents in text-messaging reproductive health quizzes . The primary study outcome was reproductive health knowledge at 3 and 15 months . Additional outcomes included self-reported pregnancy and sexual behavior . Analysis was by intent-to-treat . RESULTS From baseline to 3 months , the unidirectional intervention increased knowledge by 11 percentage points ( 95 % confidence interval [ CI ] = 7 , 15 ) and the interactive intervention by 24 percentage points ( 95 % CI = 19 , 28 ) , from a control baseline of 26 % . Although we found no changes in reproductive health outcomes overall , both unidirectional ( odds ratio [ OR ] = 0.14 ; 95 % CI = 0.03 , 0.71 ) and interactive interventions ( OR = 0.15 ; 95 % CI = 0.03 , 0.86 ) lowered odds of self-reported pregnancy for sexually active participants . CONCLUSIONS Text-messaging programs can lead to large improvements in reproductive health knowledge and have the potential to lower pregnancy risk for sexually active adolescent girls OBJECTIVES To test whether text message reminders sent to caregivers improve the effectiveness of a home micronutrient fortification program in western China . METHODS We carried out a cluster-r and omized controlled trial in 351 villages ( clusters ) in Shaanxi Province in 2013 and 2014 , enrolling children aged 6 to 12 months . We r and omly assigned each village to 1 of 3 groups : free delivery group , text messaging group , or control group . We collected information on compliance with treatments and hemoglobin concentrations from all children at baseline and 6-month follow-up . We estimated the intent-to-treat effects on compliance and child anemia using a logistic regression model . RESULTS There were 1393 eligible children . We found that assignment to the text messaging group led to an increase in full compliance ( marginal effect = 0.10 ; 95 % confidence interval [ CI ] = 0.03 , 0.16 ) compared with the free delivery group and decrease in the rate of anemia at end line relative to the control group ( marginal effect = -0.07 ; 95 % CI = -0.12 , -0.01 ) , but not relative to the free delivery group ( marginal effect = -0.03 ; 95 % CI = -0.09 , 0.03 ) . CONCLUSIONS Text messages improved compliance of caregivers to a home fortification program and children 's nutrition Background The aim of this study was to determine whether PRENACEL ( a bi-directional , mobile-phone based , short text message service ( SMS ) ) increases the coverage of recommended antenatal care ( ANC ) practice s. Methods A parallel , cluster-r and omized trial in which 20 public primary Health Care Units ( PHCUs ) were r and omly allocated to the intervention ( 10 PHCUs ) or control ( 10 PHCUs ) group . The study population included pregnant women aged 18 or above with a gestational age of 20 weeks or less . Pregnant women receiving ANC in intervention PHCUs were invited through leaflets and posters to register in PRENACEL . Women who registered in PRENACEL received a weekly set of short text messages with health education and health promotion content related to pregnancy and childbirth and were also able to clarify ANC queries through SMS . All women received routine ANC . The primary outcome was the proportion of women with high ANC Score , a composite measure of coverage of recommended ANC practice s. Chi-square or Fisher ’s exact tests and multivariate log-binomial regression were used to analyze the outcomes . Results A total of 1210 eligible women received ANC in the participating PHCUs and took part of this study ( 770 in the intervention group and 440 in the control group ) . 20.4 % ( 157/770 ) of intervention-group women registered in PRENACEL , but only 116 read all messages ( 73.9 % of women who registered in PRENACEL , 116/157 ) . The adjusted intention-to-treat analysis suggested no difference between intervention and control groups in the primary outcome ( Adjusted Relative Risk ( AdjRR ) : 1.05 ( 95 % Confidence Interval ( CI ) : 1.00–1.09 ) . Both crude and adjusted per- protocol analysis suggested a positive effect of PRENACEL ( Crude RR ( 95 % CI ) : 1.14 ( 1.06–1.22 ) , AdjRR ( 95 % CI ) : 1.12 ( 1.05–1.21 ) . The multivariate analysis also suggests that the PRENACEL group ( women who read all SMS ) had higher mean ANC score [ 48.5 ( ±4.2 ) vs 45.2 ( ±8.7 ) , p < 0.01 ] , higher proportion of women with ≥6 ANC visits ( 96.9 % vs. 84.8 % , p = 0.01 ) , and higher rates of syphilis testing ( 40.5 % vs. 24.8 % , p = 0.03 ) and HIV testing ( 46.6 % vs. 25.7 % , p < 0.01 ) during ANC . Conclusions A bi-directional , mobile-phone based , short text message service is potentially useful to improve the coverage of recommended ANC practice s , including syphilis and HIV testing . Trial registration Clinical trial registry : RBR-54zf73 , U1111–1163 - 7761.ResumoIntroduçãoO objetivo deste estudo foi determinar se o PRENACEL , um serviço bidirecional de mensagens curtas de texto ( SMS ) com base na telefonia celular , aumenta a cobertura das práticas recomendadas de cuidados pré-natais (PN).Métodosum ensaio paralelo , aleatorizado por conglomerados , no qual 20 unidades básicas de saúde ( UBS ) foram alocadas aleatoriamente para o grupo de intervenção ( 10 UBS ) ou controle ( 10 UBS ) . A população estudada incluiu gestantes com idade igual ou superior a 18 anos com idade gestacional de 20 semanas ou menos . As gestantes que receberam PN em UBS intervenção foram convidadas através de folhetos e cartazes para se inscreverem no PRENACEL . As mulheres que se registraram no PRENACEL receberam um conjunto semanal de SMS com conteúdo de educação e promoção da saúde relacionadas à gravidez e parto e também puderam esclarecer dúvidas relacionadas ao PN através de SMS . Todas as mulheres receberam PN de rotina . O desfecho primário foi a proporção de mulheres com um alto escore de PN , uma medida da cobertura das principais práticas recomendadas no PN . Result adosum total de 1.210 mulheres participaram deste estudo ( 770 no grupo de intervenção e 440 no grupo de controle ) . 20,4 % ( 157/770 ) das mulheres do grupo de intervenção demonstraram interesse e foram registradas no PRENACEL , mas apenas 116 leram as mensagens ( 73,9 % , 116/157 ) . A análise ajustada de intenção de tratamento sugeriu ausência de efeito da intervenção no desfecho primário ( Risco Relativo ( RR ) ajustado : 1,05 , Intervalo de Confiança ( IC ) de 95 % : 1,00–1,09 ) . A análise por protocol o sugeriu um efeito positivo do PRENACEL [ RR bruto ( IC 95 % ) : 1,14 ( 1,06–1,22 ) , RR ajustado ( IC 95 % ) : 1,12 ( 1,05–1,21 ) ] . A análise multivariada sugeriu que as mulheres que leram os SMS apresentaram a maior média do escore de PN [ 48,5 ( ±4,2 ) vs 45,2 ( ±8,7 ) , p < 0,01 ] , maior proporção de mulheres com ≥6 consultas ( 96,9 % vs. 84,8 % , p = 0,01 ) e maiores taxas de teste de sífilis ( 40,5 % vs. 24,8 % , p = 0,03 ) e HIV ( 46,6 % vs. 25,7 % , p < 0,01 ) durante o PN.Conclusõeso sistema PRENACEL é potencialmente útil para melhorar a cobertura das práticas recomendadas de PN , incluindo testes de sífilis e HIV Background Despite efforts to promote vaccination in low- and middle-income countries ( LMICs ) , over 20 million infants remain under-immunized and at risk for unnecessary morbidity and mortality . Mobile health technologies , such as Short Message Service ( SMS ) texts , have tremendous and untapped potential for disease management . Patient reminder systems are an important mechanism for improving childhood vaccination coverage and can be easily adapted to SMS platforms . However , current research lacks an underst and ing of the barriers and facilitators to mHealth program design , implementation , and scale in LMICs . Methods We analyzed survey data collected March-November 2016 at the enrollment visit from a r and omized controlled trial conducted at public health clinics in urban and rural Guatemala . Participants included eligible infants 6 weeks to 6 months of age receiving the first dose of the primary immunization series . At least one parent needed to own a mobile phone and be capable of deciphering SMS . Chi-square or Fisher 's exact and Student 's t-test were used to assess significance levels in demographic differences to describe factors that contribute to the feasibility of using an SMS-based vaccination reminder system . Results Of 1,088 families approached for enrollment , 871 were eligible and 720 ( 82.7 % ) participated with equal numbers of urban and rural children enrolled ; 54 parents did not own a mobile phone with SMS capability and three parents could not use SMS . There was no significant difference between urban and rural maternal mobile phone ownership ( 94.4 % vs. 93.3 % , P=0.53 ) , but more urban fathers owned mobile phones ( 72.8 % vs. 47.1 % , P<0.0001 ) and , overall , more mothers compared to fathers owned mobile phones ( 93.9 % vs. 61.1 % , P<0.0001 ) . Most families ( 90.4 % ) chose to have reminders sent to the mother . Urban participants reported more mobile phones present in the home ( P<0.0001 ) , but rural participants reported more telephone l and lines ( 34.7 % vs. 15.6 % , P<0.0001 ) . Most participants reported a daily average of ≤5 telephone calls made ( 87.4 % ) , ≤10 texts sent ( 91.0 % ) , and ≤10 texts received ( 89.9 % ) , with urban families reporting greater telephone usage ( P=0.006 , P<0.001 , and P<0.001 respectively ) . Parents preferred to make calls over sending texts ( 74.7 % vs. 25.3 % , P<0.0001 ) , with more urban families preferring text messaging ( 31.9 % vs. 18.6 % , P<0.0001 ) . Conclusions Our study results provide important insight into mobile phone access , usage , and preferences for voice and text communication across rural and urban population s of an LMIC that can be used to inform future mHealth interventions . Our findings suggest that offering a combination of more traditional communication methods with newer , modern technologies may be more effective at reminding families about vaccination visits , particularly for our rural population , and that targeting mothers for mobile phone interventions may provide the greatest benefits . Overall , our study suggests that using SMS reminders in LMICs can be a feasible tool for public health interventions Objectives To assess the effectiveness of Short Message Service ( SMS ) reminder messages on antiretroviral and cotrimoxazole prophylaxis adherence among HIV-positive youths as well as the relative effectiveness of SMS with and without a response option . Methods Eligible HIV-positive patients aged 15 to 22 years at 2 HIV clinics in Kampala , Ug and a , participated in a year-long parallel individual-r and omized controlled trial and were assigned in a 1-to-1-to-1 ratio to a weekly SMS message group , weekly SMS message with response option group , or a usual-care control group . Results We enrolled 332 participants . Electronically measured mean adherence was 67 % in the control group , 64 % in the 1-way SMS group ( 95 % confidence interval [ CI ] = 0.77 , 1.14 ) , and 61 % in the 2-way SMS group ( 95 % CI = 0.75 , 1.12 ) in an intent-to-treat analysis . Results for secondary outcomes and complete-case analysis were similarly statistically insignificant across groups . Conclusions Despite previous evidence that interventions using SMS reminders can promote antiretroviral therapy adherence , this study shows that they are not always effective in achieving behavior change . More research is needed to find out for whom , and under what conditions , they can be beneficial . Trial registration Clinical Trials.gov identifier : NCT00830622 |
714 | 27,503,423 | Conclusions : There could be a favorable characteristic of fibrosis regression in SVR patients .
However , residential fibrosis may remain an issue because of a non‐ignorable prevalence of fibrosis maintenance among these patients | Background and Aim : Virological cure becomes available for most patients with chronic hepatitis C ( CHC ) , but residual fibrosis can be an independent risk factor for liver‐related complications .
We aim ed to characterize fibrosis change in CHC patients achieved virological cure . | BACKGROUND & AIMS Liver fibrosis is an important prognostic factor in patients with hepatitis C. The effect of pegylated ( PEG ) interferon alone or its combination with ribavirin on fibrosis has not been established . METHODS We pooled individual data from 3010 naive patients with pretreatment and posttreatment biopsies from 4 r and omized trials . Ten different regimens combining st and ard interferon , PEG interferon , and ribavirin were compared . The impact of each regimen was estimated by the percentage of patients with at least 1 grade improvement in the necrosis and inflammation ( METAVIR score ) , the percentage of patients with at least 1 stage worsening in fibrosis METAVIR score , and by the fibrosis progression rate per year . RESULTS Necrosis and inflammation improvement ranged from 39 % ( interferon 24 weeks ) to 73 % ( optimized PEG 1.5 and ribavirin ; P < 0.001 ) . Fibrosis worsening ranges from 23 % ( interferon 24 weeks ) to 8 % ( optimized PEG 1.5 and ribavirin ; P < 0.001 ) . All regimens significantly reduced the fibrosis progression rates in comparison to rates before treatment . The reversal of cirrhosis was observed in 75 patients ( 49 % ) of 153 patients with baseline cirrhosis . Six factors were independently associated with the absence of significant fibrosis after treatment : baseline fibrosis stage ( odds ratio [ OR ] = 0.12 ; P < 0.0001 ) , sustained viral response ( OR = 0.36 ; P < 0.0001 ) , age < 40 years ( OR = 0.51 ; P < 0.001 ) , body mass index < 27 kg/m(2 ) ( OR = 0.65 ; P < 0.001 ) , no or minimal baseline activity ( OR = 0.70 ; P = 0.02 ) , and viral load < 3.5 millions copies per milliliter ( OR = 0.79 ; P = 0.03 ) . CONCLUSIONS PEG-interferon and ribavirin combination significantly reduces the rate of fibrosis progression in patients with hepatitis BACKGROUND & AIMS Chronic hepatitis C is both a virologic and fibrotic disease and complications can occur in patients with sustained virologic response ( SVR ) with residual fibrosis . Due to the limitations of repeated biopsies , no studies have assessed the dynamic of fibrosis before and after treatment . Using biopsy as reference , FibroTest ™ has been vali date d as a biomarker of fibrosis progression and regression , with similar prognostic values . The aim was to estimate the impact of SVR on the dynamic of fibrosis presumed by FibroTest ™ . METHODS In a prospect i ve cohort , the main end point was the 10-year regression rate of fibrosis , defined as a minimum 0.20 decrease in FibroTest ™ , equivalent to one METAVIR stage . RESULTS A total of 933 patients with both repeated FibroTest ™ and transient elastography were included . At 10 years , among the 415 patients with baseline advanced fibrosis , 49 % ( 95 % CI 33 - 64 % ) of the 108 SVR had a regression , which was greater than in the 219 non-responders [ 23 % ( 14 - 33 % ; p < 0.001 vs. SVR ) ] and not lower than in the 88 non-treated [ 45 % ( 10 - 80 % ; p = 0.39 vs. SVR ) ] patients . In all 171 SVR , cirrhosis regressed in 24/43 patients , but 15 new cirrhosis cases occurred out of 128 patients , that is only a net reduction of 5.3 % [ ( 24 - 15 ) = 9/171 ) ; ( 2.4 - 9.8 % ) ] . Four cases of primary liver cancer occurred in SVR [ 4.6 % ( 0 - 9.8 ) ] , and 13 in non-responders [ 5.6 % ( 1.5 - 9.8 ) ; p = 0.07 ] . CONCLUSIONS In patients with chronic hepatitis C , and as presumed by FibroTest ™ , virological cure was associated with slow regression of fibrosis 10years later , a disappointing 5 % decrease in cirrhosis cases , and a remaining 5 % risk of primary liver cancer BACKGROUND A sustained virological response ( SVR ) rate of 41 % has been achieved with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this r and omised trial , peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin . METHODS 1530 patients with chronic hepatitis C were assigned interferon alfa-2b ( 3 MU subcutaneously three times per week ) plus ribavirin 1000 - 1200 mg/day orally , peginterferon alfa-2b 1.5 microg/kg each week plus 800 mg/day ribavirin , or peginterferon alfa-2b 1.5 microg/kg per week for 4 weeks then 0.5 microg/kg per week plus ribavirin 1000 - 1200 mg/day for 48 weeks . The primary endpoint was the SVR rate ( undetectable hepatitis C virus [ HCV ] RNA in serum at 24-week follow-up ) . Analyses were based on patients who received at least one dose of study medication . FINDINGS The SVR rate was significantly higher ( p=0.01 for both comparisons ) in the higher-dose peginterferon group ( 274/511 [ 54 % ] ) than in the lower-dose peginterferon ( 244/514 [ 47 % ] ) or interferon ( 235/505 [ 47 % ] ) groups . Among patients with HCV genotype 1 infection , the corresponding SVR rates were 42 % ( 145/348 ) , 34 % ( 118/349 ) , and 33 % ( 114/343 ) . The rate for patients with genotype 2 and 3 infections was about 80 % for all treatment groups . Secondary analyses identified bodyweight as an important predictor of SVR , prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight ( mg/kg ) . Side-effect profiles were similar between the treatment groups . INTERPRETATION In patients with chronic hepatitis C , the most effective therapy is the combination of peginterferon alfa-2b 1.5 microg/kg per week plus ribavirin . The benefit is mostly achieved in patients with HCV genotype 1 infections Interferon and ribavirin decrease necroinflammation in chronic hepatitis C with or without virological clearance ; however , reversibility of fibrosis remains to be established . We evaluated the effect of combination therapy on virological and liver histopathological outcomes in 52 naïve patients and 79 patients unresponsive to interferon monotherapy with predominantly genotype 1 chronic hepatitis C. One hundred four patients completed interferon and ribavirin treatment after 24–48 weeks . Fifty-six paired liver biopsies ( mean biopsy interval 28 months ) were assessed by the Ishak score . Sustained virological responses were 37 % in naïve patients and 22 % in re-treated patients . In virological responders and nonresponders , fibrosis and necroinflammation scores decreased by −0.91 ( P = 0.04 ) and −0.5 ( P = 0.02 ) and by −2.8 ( P = 0.001 ) and −0.66 ( P = 0.06 ) , respectively . Interferon and ribavirin had greater benefit on fibrosis when associated with clearance of HCV RNA . Treatment strategies in virological nonresponders who show fibrosis regression should include consideration of maintenance therapy , if such treatment eventually proves to benefit histological outcomes BACKGROUND In phase 2 trials , telaprevir , a hepatitis C virus ( HCV ) genotype 1 protease inhibitor , in combination with peginterferon-ribavirin , as compared with peginterferon-ribavirin alone , has shown improved efficacy , with potential for shortening the duration of treatment in a majority of patients . METHODS In this international , phase 3 , r and omized , double-blind , placebo-controlled trial , we assigned 1088 patients with HCV genotype 1 infection who had not received previous treatment for the infection to one of three groups : a group receiving telaprevir combined with peginterferon alfa-2a and ribavirin for 12 weeks ( T12PR group ) , followed by peginterferon-ribavirin alone for 12 weeks if HCV RNA was undetectable at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point ; a group receiving telaprevir with peginterferon-ribavirin for 8 weeks and placebo with peginterferon-ribavirin for 4 weeks ( T8PR group ) , followed by 12 or 36 weeks of peginterferon-ribavirin on the basis of the same HCV RNA criteria ; or a group receiving placebo with peginterferon-ribavirin for 12 weeks , followed by 36 weeks of peginterferon-ribavirin ( PR group ) . The primary end point was the proportion of patients who had undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment ( sustained virologic response ) . RESULTS Significantly more patients in the T12PR or T8PR group than in the PR group had a sustained virologic response ( 75 % and 69 % , respectively , vs. 44 % ; P<0.001 for the comparison of the T12PR or T8PR group with the PR group ) . A total of 58 % of the patients treated with telaprevir were eligible to receive 24 weeks of total treatment . Anemia , gastrointestinal side effects , and skin rashes occurred at a higher incidence among patients receiving telaprevir than among those receiving peginterferon-ribavirin alone . The overall rate of discontinuation of the treatment regimen owing to adverse events was 10 % in the T12PR and T8PR groups and 7 % in the PR group . CONCLUSIONS Telaprevir with peginterferon-ribavirin , as compared with peginterferon-ribavirin alone , was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment , with only 24 weeks of therapy administered in the majority of patients . ( Funded by Vertex Pharmaceuticals and Tibotec ; ADVANCE Clinical Trials.gov number , NCT00627926 . ) The prognosis of chronic hepatitis C virus ( HCV ) infection is still ill‐defined . The present study prospect ively evaluated mortality and complications in a large cohort of patients with chronic hepatitis C. The study included 838 anti‐HCV and HCV‐RNA – positive patients who were followed for 50.2 ± 26.9 months ( mean ± SD ; range , 6‐122 months ) in a prospect i ve protocol . During follow‐up , 62 patients died ( 31 from liver disease and 31 from other causes ) , and 12 patients needed liver transplantation . When compared with a matched general population , hepatitis C increased mortality mainly when cirrhosis was present and in patients who were less than 50 years old at study entry . During follow‐up , a further 30 patients developed nonlethal complications of cirrhosis . By multivariate regression , survival was decreased by cirrhosis , long disease duration , history of intravenous drug abuse , and excessive alcohol consumption , whereas interferon therapy improved survival . Alanine transaminase ( ALT ) , bilirubin , sex , and genotype had no effect on survival . The risk of hepatocellular carcinoma ( HCC ) ( n = 17 ) was increased by cirrhosis and to a lesser degree by long disease duration and high bilirubin , whereas interferon therapy , genotype , and other factors had no effect . Chronic hepatitis C is a disease with considerable mortality and morbidity when cirrhosis is present at diagnosis . Patients who acquire the infection early in life have a markedly increased mortality even when cirrhosis is absent at diagnosis . The age at diagnosis therefore should play a major role in therapeutic considerations . The present data also suggest that interferon therapy has a long‐term clinical benefit , although it did not reduce the risk of liver cancer BACKGROUND / AIMS Data on hepatitis C virus ( HCV ) viral dynamics and on the effect of interferon in blocking virion production have suggested a rationale for daily administration of interferon in patients with chronic hepatitis C infection . We compared the efficacy and safety of daily interferon alfa-2b in combination with ribavirin with those of interferon alfa-2b three times a week alone or in combination with ribavirin . METHODS We r and omly assigned 321 patients with chronic hepatitis C to receive st and ard-dose interferon alfa-2b alone or in combination with ribavirin for 48 weeks or daily interferon alfa-2b ( 3 million units per day for 12 weeks then 3 million units three times per week for 24 weeks ) and ribavirin ( 36 week treatment ) . RESULTS The rate of sustained virologic response ( defined as an undetectable serum HCV-RNA level 72 weeks after initiation of treatment ) was higher in patients who received combination therapy with three times weekly interferon ( 51.7 % ) or daily interferon ( 46.1 % ) than in patients who received interferon alone ( 25 % ) ( P=0.0001 and P=0.002 , respectively ) . Independent predictive factors for sustained virologic response were combination therapy , weight , genotype and viral load . In conclusion , in patients with chronic hepatitis C , combination therapy with induction treatment ( daily interferon for 12 weeks ) and shorter duration of treatment was not different from combination therapy for 48 weeks without induction treatment . CONCLUSIONS Induction treatment with interferon for 12 weeks and combination therapy for a total duration of 36 weeks could therefore be cost effective UNLABELLED No data are available about the prediction of long-term survival using repeated noninvasive tests of liver fibrosis in chronic hepatitis C ( CHC ) . We aim ed to assess the prognostic value of 3-year liver stiffness measurement ( LSM ) , aspartate aminotransferase to platelet ratio index ( APRI ) , and fibrosis 4 ( FIB-4 ) evolution in CHC . CHC patients with two LSM ( 1,000 - 1,500 days interval ) were prospect ively included . Blood fibrosis tests APRI and FIB-4 were calculated the day of baseline ( bLSM ) and follow-up ( fLSM ) LSM . Evolution of fibrosis tests was expressed as delta : ( follow-up-baseline results ) / duration . Date and cause of death were recorded during follow-up that started the day of fLSM . In all , 1,025 patients were included . Median follow-up after fLSM was 38.0 months ( interquartile range [ IQR ] : 27.7 - 46.1 ) during which 35 patients died ( 14 liver-related death ) and seven had liver transplantation . Prognostic accuracy ( Harrell C-index ) of multivariate models including baseline and delta results was not significantly different between LSM and FIB-4 ( P ≥ 0.24 ) , whereas FIB-4 provided more accurate prognostic models than APRI ( P = 0.03 ) . By multivariate analysis including LSM variables , overall survival was independently predicted by bLSM , delta ( dLSM ) , and sustained virological response ( SVR ) . Prognosis was excellent in patients having bLSM < 7 kPa , SVR , or no increase ( < 1 kPa/year ) in 7 - 14 kPa bLSM . Prognosis was significantly impaired in patients with an increase ( ≥ 1 kPa/year ) in 7 - 14 kPa bLSM , or decrease ( ≤ 0 kPa/year ) in ≥ 14 kPa bLSM ( P = 0.949 between these two groups ) . Patients with an increase ( > 0 kPa/year ) in ≥ 14 kPa bLSM had the worst prognosis . Baseline and delta FIB-4 also identified patient subgroups with significantly different prognosis . CONCLUSION Three-year evolution of noninvasive tests of liver fibrosis has a strong prognostic value in CHC patients . These tests should be repeated to monitor patients and predict their outcome The aim of this study was to evaluate the effect of interferon‐α on liver fibrosis with an established quantitative histochemical method for determining collagen as a marker . 59 patients ( 31 men , 28 women ; 47 ± 14 yr ) with chronic non‐A , non‐B hepatitis ( 92 % with hepatitis C virus antibody ) received subcutaneous injections of 3 or 1 MU recombinant interferon‐α2b or placebo thrice weekly for 24 wk . Needle‐biopsy sections taken before and after interferon treatment were examined for histological evaluation and collagen quantitation . Values were compared with results obtained by means of morphometrical analysis of liver collagen and Knodell scoring histological index . The index of periportal and /or bridging necrosis was the only component of Knodell 's histological score significantly decreased ( p < 0.05 ) in patients treated with 3 MU interferon compared with placebo‐treated controls . The fibrosis score was not significantly changed . In contrast , liver total collagen variations measured colorimetrically and morphometrically were significantly decreased in patients treated with 3 MU and 1 MU compared with the increase observed in the placebo‐treated controls ( p < 0.05 ) . From these results , we conclude that a 6‐mo course of 3 MU or 1 MU interferon‐α2b causes slight but nonetheless significant regression of liver fibrosis as assessed on the basis of quantitative estimation of liver collagen , irrespective of other response criteria , whereas progression of liver fibrosis can be observed in the absence of treatment . ( HEPATOLOGY 1993;18:1344–1349 . Context Few studies have documented histologic regression of cirrhosis . Contribution This study describes 96 patients with chronic hepatitis C and biopsy-proven cirrhosis who were treated with an interferon-based regimen and who had at least 1 post-treatment liver biopsy . Eighteen patients had biopsy-proven regression of cirrhosis . Patients with regression had better 10-year survival rates than did patients without regression ( 100 % vs. 74 % ) . Implication Cirrhosis may be reversible in some patients with chronic hepatitis C. The Editors Single or multifactorial damage to the liver ultimately leads to cirrhosis and its complications , especially hepatocellular carcinoma ( 13 ) . Different types of evidence histologic ; morphologic ( as assessed by abdominal ultrasonography or digestive endoscopy ) ; and biochemical ( as assessed by measurement of hyaluronate , procollagen III peptide , prothrombin time , and platelets ) , including analyses of native liverssupport the idea that cirrhosis can be reversed , provided that the underlying disease is controlled ( 58 ) . Nevertheless , whether cirrhosis regresses is still debated ( 9 , 10 ) . To provide definitive support for this concept , we evaluated the relation between histologic regression of cirrhosis and clinical outcome in patients treated for chronic hepatitis C. Methods Study Design We established a cohort of 143 patients with biopsy-proven cirrhosis ( METAVIR F4 ) who received specific treatment between 1988 and 2001 at a single hepatology unit in a tertiary care center in France and who underwent a second liver biopsy to assess the effect of treatment on cirrhosis ( Appendix Figure ) ( 6 , 8 , 11 ) . All patients in this cohort currently undergo prospect i ve follow-up and are seen by a senior hepatologist at least every 6 months . The institutional review board of our hospital approved the past and present studies , and all patients gave informed consent . Appendix Figure . Study flow diagram . We included patients who met the following criteria : ChildPugh class A cirrhosis related to chronic hepatitis C ; absence of hepatitis B co-infection ; absence of immunosuppression ( HIV-associated infection , long-term hemodialysis , organ transplantation , immunosuppressive therapy ) ; and treatment with conventional -interferon or pegylated interferon , with or without ribavirin . The exclusion criteria were age older than 70 years at the time of diagnosis of cirrhosis and previous liver-related complications . Sustained virologic response was defined as undetectable hepatitis C virus RNA on the latest available assaying technique and normal alanine aminotransferase level 24 weeks after the end of treatment and during follow-up . Patients who did not fulfill these criteria were classified as nonresponders and did not receive long-term treatment . Liver disease was staged and grade d according to the METAVIR score ( 12 ) , which combines an activity stage from 0 to 3 and a fibrosis grade from 0 to 4 ( 4 corresponds to cirrhosis ) . Regression of cirrhosis was defined as a decrease in the score from 4 to 2 or fewer METAVIR fibrosis units to avoid the 15 % rate of false-negative results in patients with F3 disease ( 13 , 14 ) . Patients underwent clinical and biological evaluation , including measurement of aminotransferase , bilirubin , albumin , prothrombin time , platelet , and hepatitis C viral load at each visit . All patients were screened for hepatocellular carcinoma with ultrasonography and had -fetoprotein measured every 6 months . The diagnosis of hepatocellular carcinoma followed the guidelines of the European Association for the Study of the Liver ( 15 ) . Hepatic encephalopathy was defined clinical ly ( 16 ) . Ascites was diagnosed by clinical examination and ultrasonography . The source of gastroesophageal bleeding was confirmed by endoscopy . Outcome Measures Our main goal was to evaluate the effect of regression of cirrhosis on a composite end point of liver-related complications ( ascites , hepatic encephalopathy , variceal bleeding , spontaneous bacterial peritonitis , hepatocellular carcinoma , liver transplantation ) and death from liver-related causes . For patients with more than 1 event , only the first event was analyzed . The incidence of liver-related deaths or transplantation was analyzed as a secondary end point . Statistical Analysis Total duration of follow-up was calculated from the date of the first liver biopsy until death , last consultation , or liver transplantation until November 2006 . Eight patients ( 8 % ) were not followed in our unit as of this date after a median follow-up of 96 months ( range , 36 to 127 months ) . These patients were censored at the time of the last visit . The time from diagnosis of cirrhosis ( time of the index biopsy ) to liver-related complications or to the date when the data were censored was plotted according to groups by using KaplanMeier estimates , and P values were computed with the log-rank test . All P values are 2-sided , and the type I error was set at 5 % . Continuous values are presented as medians and interquartile ranges and categorical variables as counts and proportions . The differences between groups were assessed with the Fisher exact test and the MannWhitney U test . All statistical analyses were performed by using SPSS software , version 16 ( SPSS , Chicago , Illinois ) . Role of the Funding Source This study was funded by the French Agence Nationale de la Recherche ( ANR ) . The funding source had no role in the design , analysis , or interpretation of the study or in the decision to su bmi t the manuscript for publication . Results Sample Ninety-six patients fulfilled the inclusion criteria ( Table 1 ) . All had ChildPugh class A biopsy-proven cirrhosis at enrollment and thereafter received specific therapy . The median interval between the first liver biopsy and treatment was 2 months ( interquartile range , 0 to 6 months ) . Sixty-one patients ( 64 % ) received interferon monotherapy , 34 ( 35 % ) received interferon and ribavirin , and 1 ( 1 % ) received pegylated interferon and ribavirin . Eighty-two patients ( 85 % ) did not respond to the first treatment course ; of these , 47 ( 49 % ) received at least 1 more treatment course . Thirty-nine patients ( 41 % ) achieved a sustained virologic response , and 57 ( 59 % ) did not . Table 1 . Patient Characteristics at Baseline Histologic Outcome The median interval between the end of treatment and the second liver biopsy was 17 months . The median length of the liver biopsy sample s was 15 mm ( interquartile range , 10 to 20 mm ) both before and after treatment ( P= 0.86 , Wilcoxon signed-rank test ) . In terms of fibrosis scores , 69 liver biopsies ( 71.9 % ) showed persistent cirrhosis ( METAVIR fibrosis stage 4 ) , 9 ( 9.4 % ) showed extensive fibrosis ( stage 3 ) , 10 ( 10.4 % ) showed intermediate fibrosis ( stage 2 ) , 7 ( 7.3 % ) showed moderate fibrosis ( stage 1 ) , and 1 ( 1 % ) showed no fibrosis ( stage 0 ) . Of the 18 patients with regression of cirrhosis on the second liver biopsy ( METAVIR fibrosis stage 0 , 1 , or 2 ) , 17 ( 94.4 % ) had long-term response to therapy and 1 had biochemical response ( normal liver function tests and no detectable activity on liver biopsy but persistent viremia ) to antihepatitis C therapy . Clinical Outcome The median follow-up was 118 months ( interquartile range , 86 to 138 months ) , and total follow-up was 900 patient-years . The time from achievement of sustained virologic response to the end of follow-up was similar between patients with and those without regression of cirrhosis ( P= 0.38 ) . During follow-up , 27 ( 35 % ) patients with persistent cirrhosis developed at least 1 cirrhosis-related complication ( Table 2 ) . The incidence of liver-related complications , including hepatocellular carcinoma , was lower in patients with a sustained virologic response ( Figure , top ) . Nevertheless , 4 patients with hepatitis Crelated cirrhosis developed a liver-related event , including variceal bleeding ( 1 patient ) and hepatocellular carcinoma ( 3 patients ) ; all had antihepatitis B core antigen antibodies . In contrast , patients with regression of cirrhosis had no complications ( Figure , bottom ) . The incidence of cirrhosis-related complications per 100 patient-years was 1.14 in patients with sustained virologic response and 4.63 in those without sustained virologic response ( P= 0.009 ) ; respective values in patients with and those without regression of cirrhosis were 0 and 4 ( P= 0.002 ) . Table 2 . Clinical Outcomes , by Virologic and Histologic Response Figure . KaplanMeier estimates of time to a liver-related event and death in patients with or without a sustained virologic response ( top ) and in patients with or without regression of cirrhosis ( bottom ) . Liver-related events were hepatocellular carcinoma , hepatic encephalopathy , variceal bleeding , ascites , spontaneous bacterial peritonitis , and liver transplantation . During follow-up , 22 patients ( 23 % ) without regression died ( n= 16 [ 17 % ] ) or underwent a liver transplantation ( n= 6 [ 6 % ] ) , whereas neither of these events occurred in the 18 patients with regression ( P= 0.010 ) . The incidence of liver-related death or liver transplantation per 100 patient-years was 0.85 in patients with sustained virologic response and 3.43 in those without sustained virologic response ( P= 0.004 , log-rank test ) ; respective values in patients with and those without cirrhosis were 0 and 2.96 ( P= 0.025 , log-rank test ) . Among the 6 patients who had liver transplantation , 5 survived and 1 died during the perioperative period . Four patients died of nonliver-related causes . One patient with regression of cirrhosis died of myocardial infa rct ion . Discussion During more than 10 years of follow-up in 96 patients with treated hepatitis Crelated cirrhosis , 18 patients achieved histologically proven regression . The absence of liver-related morbidity and mortality in these patients supports the concept of cirrhosis reversal . Persistence of cirrhosis carries a risk for hepatocellular carcinoma , which warrants regular screening . Regression of hepatitis Crelated cirrhosis after treatment ranges from 10 % Background Studies of viral hepatitis C have suggested that fibrosis can regress , at least in patients with sustained virological response . A recent study suggested that cirrhosis was reversible in sustained and non-virological responders . Aim To study fibrosis progression rate and cirrhosis reversion in patients treated for severe fibrosis with interferon or interferon + ribavirin . Patients and methods Ninety-nine patients were treated with interferon + ribavirin and 64 with interferon . The Metavir fibrosis score and the semiquantitative fibrosis score ( SFS ) were used to assess fibrosis . Results In sustained responders , fibrosis progression rate decreased from 0.26 Metavir unit ( interquartile range : 0.19–0.34 ) to −0.67 ( −0.67 to 0 ) ( P < 0.0001 ) and from 0.81 SFS unit ( 0.48–1.13 ) to −1.33 ( −3.67 to 0 ) ( P < 0.0001 ) . In non-responders , fibrosis progression rate decreased from 0.25 Metavir unit ( 0.17–0.33 ) before treatment to 0 ( 0–0 ) during treatment ( P = 0.002 ) and from 0.63 SFS unit ( 0.49–1.12 ) to 0 ( −2.67–1.33 ) ( P = 0.18 ) . Six out of 18 ( 33 % ) sustained virological responders and four of 43 ( 9 % ) non-responders regressed from cirrhosis ( F4 ) to severe fibrosis ( F3 ) ( P = 0.058 ) . No patient with cirrhosis had a decrease of Metavir fibrosis score of 2 points . Conclusion Interferon can slow fibrosis progression in sustained virological responders with severe fibrosis . In patients with a non-virological response and treated for 12 months the fibrosis progression rate was nil , meaning that only fibrosis stabilization could be obtained in these patients . Then , longer treatment duration ( 3–4 years ) could be evaluated in non-virological responders Liver fibrosis and activity indexes were vali date d in patients infected by hepatitis C virus ( HCV ) nontreated and treated by interferon . The aim was to vali date their usefulness as surrogate markers of histologic features using the data of a r and omized trial of combination peginterferon alfa‐2b and ribavirin . Three hundred fifty‐two patients who had had 2 interpretable liver biopsies and stored serum sample before and after treatment were selected . Two hundred eight patients received peginterferon alfa‐2b 1.5 mcg per kg and ribavirin and 144 patients interferon alfa‐2b 3 MU three times a week and ribavirin for 48 weeks . A fibrosis and an activity index combining 5 and 6 biochemical markers were assessed at baseline and at end of follow‐up ( 24 weeks after treatment ) . The biochemical markers have significant predictive values both for the diagnosis of fibrosis and for activity . For the diagnosis of bridging fibrosis and /or moderate necroinflammatory activity , the area under the receiver operating characteristics curve of the activity index was 0.76 ± 0.03 at baseline and 0.82 ± 0.02 at end of follow‐up . A cutoff of activity index at 0.30 ( range , 0.00‐1.00 ) had 90 % sensitivity and 88 % positive predictive value for the diagnosis of bridging fibrosis or moderate necroinflammatory activity . Sensitivity analyses with biopsy specimens of size greater than 15 mm suggest that a part of discordances between biochemical markers and histology were due to biopsy specimen sampling error . In conclusion , these biochemical markers of fibrosis and activity could be used as surrogate markers for liver biopsy in patients with chronic hepatitis C , both for the initial evaluation and for follow‐up BACKGROUND There is a need for interferon-free treatment regimens for hepatitis C virus ( HCV ) infection . The goal of this study was to evaluate ABT-450 , a potent HCV NS3 protease inhibitor , combined with low-dose ritonavir ( ABT-450/r ) , in addition to ABT-333 , a nonnucleoside NS5B polymerase inhibitor , and ribavirin , for the treatment of HCV infection . METHODS We conducted a 12-week , phase 2a , open-label study involving patients who had HCV genotype 1 infection without cirrhosis . All patients received ABT-333 ( 400 mg twice daily ) and ribavirin ( 1000 to 1200 mg per day ) and one of two daily doses of ABT-450/r . Groups 1 and 2 included previously untreated patients ; group 1 received 250 mg of ABT-450 and 100 mg of ritonavir , and group 2 received 150 mg and 100 mg , respectively . Group 3 , which included patients who had had a null or partial response to previous therapy with peginterferon and ribavirin , received daily doses of 150 mg of ABT-450 and 100 mg of ritonavir . The primary end point was an undetectable level of HCV RNA from week 4 through week 12 ( extended rapid virologic response ) . RESULTS A total of 17 of the 19 patients in group 1 ( 89 % ) and 11 of the 14 in group 2 ( 79 % ) had an extended rapid virologic response ; a sustained virologic response 12 weeks after the end of treatment was achieved in 95 % and 93 % of the patients , respectively . In group 3 , 10 of 17 patients ( 59 % ) had an extended rapid virologic response , and 8 ( 47 % ) had a sustained virologic response 12 weeks after therapy ; 6 patients had virologic breakthrough , and 3 had a relapse . Adverse events included abnormalities in liver-function tests , fatigue , nausea , headache , dizziness , insomnia , pruritus , rash , and vomiting . CONCLUSIONS This preliminary study suggests that 12 weeks of therapy with a combination of a protease inhibitor , a nonnucleoside polymerase inhibitor , and ribavirin may be effective for treatment of HCV genotype 1 infection . ( Funded by Abbott ; Clinical Trials.gov number , NCT01306617 . ) |
715 | 32,152,763 | eHealth could provide useful services for supporting colorectal cancer survivors . | eHealth could potentially support colorectal cancer survivors ; however , little is known regarding the overall recent eHealth systems for colorectal cancer survivors .
The present study was conducted to address which types of eHealth supports have been provided to colorectal cancer survivors in the past two decades . | Background Patients often seek other patients ’ experiences with the disease . The Internet provides a wide range of opportunities to share and learn about other people ’s health and illness experiences via blogs or patient-initiated online discussion groups . There also exists a range of medical information devices that include experiential patient information . However , there are serious concerns about the use of such experiential information because narratives of others may be powerful and pervasive tools that may hinder informed decision making . The international research network DIPEx ( Data base of Individual Patients ’ Experiences ) aims to provide scientifically based online information on people ’s experiences with health and illness to fulfill patients ’ needs for experiential information , while ensuring that the presented information includes a wide variety of possible experiences . Objective The aim is to evaluate the colorectal cancer module of the German DIPEx website krankheitserfahrungen.de with regard to self-efficacy for coping with cancer and patient competence . Methods In 2015 , a Web-based r and omized controlled trial was conducted using a two-group between-subjects design and repeated measures . The study sample consisted of individuals who had been diagnosed with colorectal cancer within the past 3 years or who had metastasis or recurrent disease . Outcome measures included self-efficacy for coping with cancer and patient competence . Participants were r and omly assigned to either an intervention group that had immediate access to the colorectal cancer module for 2 weeks or to a waiting list control group . Outcome criteria were measured at baseline before r and omization and at 2 weeks and 6 weeks Results The study r and omized 212 persons . On average , participants were 54 ( SD 11.1 ) years old , 58.8 % ( 124/211 ) were female , and 73.6 % ( 156/212 ) had read or heard stories of other patients online before entering the study , thus excluding any influence of the colorectal cancer module on krankheitserfahrungen.de . No intervention effects were found at 2 and 6 weeks after baseline . Conclusions The results of this study do not support the hypothesis that the website studied may increase self-efficacy for coping with cancer or patient competencies such as self-regulation or managing emotional distress . Possible explanations may involve characteristics of the website itself , its use by participants , or method ological reasons . Future studies aim ed at evaluating potential effects of websites providing patient experiences on the basis of method ological principles such as those of DIPEx might profit from extending the range of outcome measures , from including additional measures of website usage behavior and users ’ motivation , and from exp and ing concepts , such as patient competency to include items that more directly reflect patients ’ perceived effects of using such a website . Trial Registration Clinical trials.gov NCT02157454 ; https:// clinical trials.gov/ct2/show/NCT02157454 ( Archived by WebCite at http://www.webcitation.org/6syrvwXxi Background The use of a mobile health care application , the delivery of health care or health care‐related services through the use of portable devices , to manage functional loss , treatment‐related toxicities , and impaired quality of life in cancer patients during chemotherapy through supervised self‐management has been increasing . The aim of the present study was to evaluate the efficacy and feasibility of comprehensive mobile health care using a tailored rehabilitation program for colorectal cancer patients undergoing active chemotherapy . Patients and Methods A total of 102 colorectal cancer patients undergoing chemotherapy underwent 12 weeks of smartphone aftercare through provision of a mobile application and wearable device that included a rehabilitation exercise program and information on their disease and treatment . The grip strength test , 30‐second chair st and test , 2‐minute walk test , amount of physical activity ( International Physical Activity Question naire short‐form ) , quality of life ( European Organization for Research and Treatment of Cancer Quality of Life Question naire C30 ) , and nutritional status ( Patient‐generated Subjective Global Assessment ) were assessed and measured at baseline , at mid‐intervention ( 6 weeks ) , and at completion of the intervention ( 12 weeks ) . The rehabilitation exercise intensity was adjusted by the test results at every assessment and through real‐time communication between the patients and clinicians . Results Of the 102 patients , 75 completed all 12 weeks of the smartphone aftercare rehabilitation program . The lower extremity strength ( P < .001 ) and cardiorespiratory endurance ( P < .001 ) was significantly improved . Fatigue ( P < .007 ) and nausea/vomiting ( P < .040 ) symptoms were significantly relieved after the program . Conclusion A tailored rehabilitation exercise program provided through a comprehensive mobile health care application was effective in improving patients ' physical capacity and treatment‐related symptoms even during active chemotherapy . Micro‐ Abstract The use of mobile health care applications is a method increasing in use in the cancer care continuum from cancer prevention to cancer diagnosis , cancer treatment , and cancer survivorship . However , no clinical study has yet investigated the effects and feasibility of a smartphone application‐based personalized exercise intervention for colorectal cancer patients undergoing chemotherapy . In 75 colorectal cancer patients undergoing active chemotherapy , a rehabilitation program using a mobile health care application on a wearable device was effective in improving physical function and relieving cancer‐ and cancer treatment‐related toxicities , regardless of the chemotherapy duration Background Cancer survivors have to deal with a wide range of physical symptoms , psychological , social and existential concerns , and lifestyle issues related to cancer and its treatment . Therefore , it is essential that they have access to optimal supportive care services . The eHealth self-management application Oncokompas was developed to support cancer survivors with where they need to turn to for advice and guidance , as well as to increase their knowledge on the availability of optimal support . A r and omised controlled trial will be conducted to assess the efficacy , cost-utility and reach of Oncokompas as an eHealth self-management application compared with care as usual among cancer survivors . Methods / design Adult cancer survivors diagnosed with breast , colorectal or head and neck cancer or lymphoma who are at 3 months to 5 years since curative treatment will be included . In total , 544 cancer survivors will be r and omly assigned to the intervention group or a wait-list control group . The primary outcome measure is patient activation . Secondary outcome measures include self-efficacy , personal control , perceived patient-physician interaction , need for supportive care , mental adjustment to cancer and health-related quality of life . Furthermore , cost-utility outcomes will be assessed . Reach is defined as the percentage of cancer survivors who get access to Oncokompas within the context of this trial . Question naires will be administered at baseline , post-intervention and at 3- and 6-month follow-up . Discussion In this study , we will evaluate the efficacy and cost-utility of Oncokompas among cancer survivors , as well as the reach of Oncokompas . These are essential first steps in the translation of research into practice and contribute to sustainable adoption , implementation and maintenance of an evidence -based Oncokompas . Trial registration Netherl and s Trial Register identifier : NTR5774 . Registered on 8 March 2016 Background Cancer and cancer treatment coincide with substantial negative physical , psychological and psychosocial problems . Physical activity ( PA ) can positively affect the negative effects of cancer and cancer treatment and thereby increase quality of life in CPS . Nevertheless , only a minority of CPS meet PA guidelines . We developed the OncoActive ( OncoActief in Dutch ) intervention : a computer-tailored PA program to stimulate PA in prostate and colorectal CPS , because to our knowledge there are only a few PA interventions for these specific cancer types in the Netherl and s Methods The OncoActive intervention was developed through systematic adaptation of a proven effective , evidence -based , computer-tailored PA intervention for adults over fifty , called Active Plus . The Intervention Mapping ( IM ) protocol was used to guide the systematic adaptation . A literature study and interviews with prostate and colorectal CPS and health care professionals revealed that both general and cancer-specific PA determinants are important and should be addressed . Change objectives , theoretical methods and applications and the actual program content were adapted to address the specific needs , beliefs and cancer-related issues of prostate and colorectal CPS . Intervention participants received tailored PA advice three times , on internet and with printed material s , and a pedometer to set goals to improve PA . Pre- and pilot tests showed that the intervention was highly appreciated ( target group ) and regarded safe and feasible ( healthcare professionals ) . The effectiveness of the intervention is being evaluated in a r and omized controlled trial ( RCT ) ( n = 428 ) , consisting of an intervention group and a usual care waiting-list control group , with follow-up measurements at three , six and twelve months . Participants are recruited from seventeen hospitals and with posters , flyers and calls in several media . Discussion Using the Intervention Mapping protocol result ed in a systematic ally adapted , theory and evidence -based intervention providing tailored PA advice to prostate and colorectal CPS . If the intervention turns out to be effective in increasing PA , as evaluated in a RCT , possibilities for nationwide implementation and extension to other cancer types will be explored . Trial registration The study is registered in the Dutch Trial Register ( NTR4296 ) on November 23rd 2013 and can be accessed at http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=4296 Background / Objective : Colorectal and gynecologic cancer survivors are at cardiovascular risk due to comorbidities and sedentary behaviour , warranting a feasible intervention to increase physical activity . The Health Action Process Approach ( HAPA ) is a promising theoretical framework for health behaviour change , and wearable physical activity trackers offer a novel means of self-monitoring physical activity for cancer survivors . Method : Sixty-eight survivors of colorectal and gynecologic cancer will be r and omised into 12-week intervention and control groups . Intervention group participants will receive : a Fitbit Alta ™ to monitor physical activity , HAPA-based group sessions , booklet , and support phone-call . Participants in the control group will only receive the HAPA-based booklet . Physical activity ( using accelerometers ) , blood pressure , BMI , and HAPA constructs will be assessed at baseline , 12-weeks ( post-intervention ) and 24-weeks ( follow-up ) . Data analysis will use the Group x Time interaction from a General Linear Mixed Model analysis . Conclusions : Physical activity interventions that are acceptable and have robust theoretical underpinnings show promise for improving the health of cancer survivors Purpose This r and omized controlled trial evaluated the impact of SurvivorCHESS , an eHealth intervention , on physical activity in colon cancer survivors and to explore the impact of SurvivorCHESS on quality of life and distress . Methods This was a two-arm single-blinded multi-site r and omized controlled trial comparing a control group to an intervention group receiving a smartphone with the SurvivorCHESS program . Results Participants using SurvivorCHESS ( n = 144 ) increased their moderate to vigorous physical activities from 19.4 min at baseline to 50 min compared to the control group ( n = 140 ) increasing from 15.5 to 40.3 min at 6 months ( p = .083 ) but was not sustained 3 months after the study ended . No significant differences were found between groups over time for quality of life or distress items . Reports of physical symptoms were greater than other categories for distress items . Patients who had a higher body mass index and number of comorbid conditions were less likely to increase their physical activity . Self-determination theory including autonomous motivation and relatedness was not associated with the outcomes . Conclusions Physical activity did increase over time in both groups and was not significantly different with the use of the eHealth intervention , SurvivorCHESS , compared to the control group . The amount of SurvivorCHESS use was not associated with physical activity . Implication s for cancer survivorsIncreasing physical activity in colon cancer survivors has the potential to improve quality of life and reduce recurrences . Using smartphone-tracking devices may be useful in helping to change this health behavior Introduction While some evidence exists that real-time remote symptom monitoring devices can decrease morbidity and prevent unplanned admissions in oncology patients , overall , these studies have significant method ological weaknesses . The electronic Symptom Management using the Advanced Symptom Management System ( ASyMS ) Remote Technology ( eSMART ) study is design ed to specifically address these weaknesses with an appropriately powered , repeated- measures , parallel-group stratified r and omised controlled trial of oncology patients . Methods and analysis A total of 1108 patients scheduled to commence first-line chemotherapy ( CTX ) for breast , colorectal or haematological cancer will be recruited from multiple sites across five European countries . Patients will be r and omised ( 1:1 ) to the ASyMS intervention ( intervention group ) or to st and ard care currently available at each site ( control group ) . Patients in the control and intervention groups will complete a demographic and clinical question naire , as well as a set of valid and reliable electronic patient-reported outcome measures at enrolment , after each of their CTX cycles ( up to a maximum of six cycles ) and at 3 , 6 , 9 and 12 months after completion of their sixth cycle of CTX . Outcomes that will be assessed include symptom burden ( primary outcome ) , quality of life , supportive care needs , anxiety , self-care self-efficacy , work limitations and cost effectiveness and , from a health professional perspective , changes in clinical practice ( secondary outcomes ) . Ethics and dissemination Ethical approval will be obtained prior to the implementation of all major study amendments . Applications will be su bmi tted to all of the ethics committees that granted initial approval . eSMART received approval from the relevant ethics committees at all of the clinical sites across the five participating countries . In collaboration with the European Cancer Patient Coalition ( ECPC ) , the trial results will be disseminated through publications in scientific journals , presentations at international conferences , and postings on the eSMART website and other relevant clinician and consumer websites ; establishment of an eSMART website ( www.esmartproject.eu ) with publicly accessible general information ; creation of an eSMART Twitter H and le , and production of a toolkit for implementing/utilising the ASyMS technology in a variety of clinical practice s and other transferable health care context s. Trial registration number NCT02356081 Background Mobile health apps have emerged as supportive tools in the management of advanced cancers . However , only a few apps have self-monitoring features , and they are not st and ardized and vali date d. Objective This study aim ed to develop and vali date a multidisciplinary mobile care system with self-monitoring features that can be useful for patients with advanced gastrointestinal cancer . Methods The development of the multidisciplinary mobile health management system was divided into 3 steps . First , the service scope was set up , and the measurement tools were st and ardized . Second , the service flow of the mobile care system was organized . Third , the mobile app ( Life Manager ) was developed . The app was developed to achieve 3 major clinical goals : support for quality of life , nutrition , and rehabilitation . Three main functional themes were developed to achieve clinical goals : a to-do list , health education , and in-app chat . Thirteen clinical ly oriented measures were included : the modified Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events question naire , Scored Patient-Generated Subjective Global Assessment ( PG-SGA ) , distress , European Organization for Research and Treatment of Cancer Quality of Life Question naire , International Physical Activity Question naire – Short Form , Low anterior resection syndrome score , satisfaction rate , etc . To vali date the system , a prospect i ve observational study was conducted . Patients with gastric cancer or colon cancer undergoing chemotherapy were recruited . We followed the subjects for 12 weeks , and selected clinical measures were taken online and offline . Results After the development process , a multidisciplinary app , the Life Manager , was launched . For evaluation , 203 patients were recruited for the study , of whom 101 ( 49.8 % ) had gastric cancer , and 102 ( 50.2 % ) were receiving palliative care . Most patients were in their fifties ( 35.5 % ) , and 128 ( 63.1 % ) were male . Overall , 176 subjects ( 86.7 % ) completed the study . Among subjects who dropped out , the most common reason was the change of patient ’s clinical condition ( 51.9 % ) . During the study period , subjects received multiple health education sessions . For the gastric cancer group , the “ general gastric cancer education ” was most frequently viewed ( 322 times ) , and for the colon cancer group , the “ warming-up exercise ” was most viewed ( 340 times ) . Of 13 measurements taken from subjects , 9 were taken offline ( response rate : 52.0 % to 90.1 % ) , and 3 were taken online ( response rate : 17.6 % to 57.4 % ) . The overall satisfaction rate among subjects was favorable and ranged from 3.93 ( SD 0.88 ) to 4.01 ( SD 0.87 ) on the 5-point Likert scale . Conclusions A multidisciplinary mobile care system for patients with advanced gastrointestinal cancer was developed with clinical ly oriented measures . A prospect i ve study was performed for its evaluation , which showed favorable satisfaction Summary Purpose Half of adult cancer survivors under age 50 years are obese . Excess body weight is associated with cancer recurrence , and effective weight loss interventions for younger cancer survivors are needed . Commercially available , online weight loss programmes are readily accessible , but few have been studied in this population . This study employed a single‐arm , pre‐post intervention ( baseline‐6 month/baseline‐12 month comparisons ) to preliminarily explore feasibility , efficacy and safety of an online , commercially available weight loss programme in breast ( n = 30 ) and testicular ( n = 16 ) cancer survivors under age 50 years . Methods The intervention included three daily components : exercise , nutritional/behavioural modification strategies and health lessons . Intention‐to‐treat and completers analyses were conducted . Feasibility was measured by participation ( number of participants enrolled/number screened ) , retention ( number of participants attending 6/12 month study visit/number of enrolled ) and self‐reported adherence rates ( average of mean percent adherence to each of the three intervention components ) . Efficacy was assessed by changes in initial weight ( percent weight loss ) . Safety was assessed by adverse events . Results The mean participation rate was 42 % . The retention rate was 59 % at 6 and 49 % at 12 months . The adherence rate for all participants ( completers/dropouts/lost‐to‐follow‐up ) was 50.1 % at 6 and 44 % at 12 months . Completers reported adherence rates of 68 % at 12 months . Study participants lost 5.3 % body weight at 12 months ; completers lost 9 % . Only three unexpected adverse events ( unrelated to the intervention ) were reported . Conclusion Clinical ly significant weight loss was observed , although retention rates were low . Findings generally support preliminary feasibility , efficacy and safety of this online weight loss programme , and future r and omized control trials should be explored BACKGROUND Physical activity ( PA ) may be important for preventing chronic diseases for adolescent and young adult ( AYA ) childhood cancer survivors . R and omized controlled trials ( RCTs ) of PA interventions for AYA survivors are sparse , but necessary to determine effective programs for increasing PA among this population . Thus , we conducted a pilot RCT , testing the feasibility of a mobile health ( mHealth ) intervention to promote PA among AYA survivors . PROCEDURE We recruited 14- to 18-year-olds who were ≥1-year post cancer therapy from Seattle Children 's Hospital . The 10-week intervention consisted of a wearable PA-tracking device ( Fitbit Flex ) and a peer-based virtual support group ( Facebook group ) . Research staff helped set step goals and awarded badges weekly . Controls received usual care . Baseline assessment s occurred before r and omization and follow-up assessment s occurred during weeks 8 - 10 of the intervention period . Feasibility criteria are defined below . Qualitative interviews assessed acceptability . Exploratory outcomes included PA , quality of life , and motivation for PA . RESULTS All feasibility criteria were met : we recruited 60 survivors , intervention participants wore the Fitbit on the majority ( 71.5 % ) of intervention days , and ≥90 % of all participants completed question naires . Qualitative data confirmed intervention acceptability . Exploratory analyses found no significant adjusted group differences for change in moderate-to-vigorous PA ( 4.4 vs. 5.0 min/day ; P = 0.92 ) or sedentary time ( -4.5 vs. 1.0 min/day ; P = 0.73 ) , comparing intervention subjects to controls . Some modest differences were found for select subscales of quality of life and motivation for PA . CONCLUSIONS This mHealth PA intervention was feasible and acceptable to AYA childhood cancer survivors and warrants a fully powered RCT Background : Most programs addressing psychosocial concerns of cancer survivors are in-person programs that are expensive to deliver , have limited availability , and seldom deal with caregivers ’ concerns . Objective : This study examined the feasibility of translating an efficacious nurse-delivered program ( FOCUS Program ) for patients and their caregivers to a tailored , dyadic Web-based format . Specific aims were to ( 1 ) test the preliminary effects of the Web-based intervention on patient and caregiver outcomes , ( 2 ) examine participants ’ program satisfaction , and ( 3 ) determine the feasibility of using a Web-based delivery format . Methods : A phase 2 feasibility study was conducted with cancer patients ( lung , breast , colorectal , prostate ) and their family caregivers ( N = 38 dyads ) . The Web-based intervention provided information and support tailored to the unique characteristics of each patient , caregiver , and their dyadic relationship . Primary outcomes were emotional distress and quality of life . Secondary outcomes were benefits of illness/caregiving , communication , support , and self-efficacy . Analyses included descriptive statistics and repeated- measures analysis of variance . Results : Dyads had a significant decrease in emotional distress , increase in quality of life , and perceived more benefits of illness/caregiving . Caregivers also had significant improvement in self-efficacy . There were no changes in communication . Participants were satisfied with program usability , but recommended additional content . Conclusions : It was possible to translate a clinician-delivered program to a Web-based format that was easy to use and had positive effects on dyadic outcomes . Implication s for Practice : The Web-based program is a promising way to provide psychosocial care to more patients and caregivers using fewer personnel . It needs further testing in a larger r and omized clinical trial Purpose Cognitive impairment is reported frequently by cancer survivors . There are no proven treatments . We evaluated a cognitive rehabilitation program ( Insight ) and compared it with st and ard care in cancer survivors self-reporting cognitive symptoms . Patients and Methods We recruited adult cancer survivors with a primary malignancy ( excluding central nervous system malignancies ) who had completed three or more cycles of adjuvant chemotherapy in the previous 6 to 60 months and reported persistent cognitive symptoms . All participants received a 30-minute telephone consultation and were then r and omly assigned to the 15-week , home-based intervention or to st and ard care . Primary outcome was self-reported cognitive function ( Functional Assessment of Cancer Therapy Cognitive Function [ FACT-COG ] perceived cognitive impairment [ PCI ] subscale ) : difference between groups after intervention ( T2 ) and 6 months later ( T3 ) . Results A total of 242 participants were r and omly assigned : median age , 53 years ; 95 % female . The primary outcome of difference in FACT-COG PCI was significant , with less PCI in the intervention group at T2 ( P < .001 ) . This difference was sustained at T3 ( P < .001 ) . At T2 , there was a significant difference in all FACT-COG subscales , favoring the intervention . Neuropsychological results were not significantly different between the groups at T2 or T3 . There were significantly lower levels of anxiety/depression and fatigue in the intervention group at T2 . There were significant improvements in stress in the intervention group at both time points . There was no significant difference in quality of life between the groups at T2 , but the intervention group had better quality of life at T3 . Conclusion The intervention , Insight , led to improvements in cognitive symptoms compared with st and ard care . To our knowledge , this is the first large r and omized controlled trial showing an improvement in self-reported cognitive function in cancer survivors , indicating that this intervention is a feasible treatment Objective : To examine the effects of an internet-delivered , distance-based physical activity ( PA ) behaviour change programme on motivation to perform PA in cancer survivors . Design : Breast , prostate and colorectal cancer survivors ( N = 95 ) were r and omized to either an online Theory of Planned Behaviour (TPB)-based PA behaviour change programme ( UCAN ) or usual care . Main Outcome Measures : Motivational variables from the TPB including intention , planning , attitude , subjective norm , perceived behavioural control and underlying beliefs . Results : UCAN had significant negative effects on self-efficacy ( −.7 ; 95 % CI = −1.2 to −.1 ; d = −.53 , p = .019 ) , affective attitude ( −.4 ; 95 % CI = −.8 to −.0 ; d = −.45 , p = .044 ) , instrumental attitude ( −.5 ; 95 % CI = −.9 to −.1 ; d = −.43 , p = .026 ) and confidence to perform PA in bad weather ( −.8 ; 95 % CI = −1.6 to −.1 ; d = −.49 , p = .030 ) , despite health issues ( −.7 ; 95 % CI = −1.3 to −.1 ; d = −.48 , p = .031 ) , despite pain/soreness ( −.7 ; 95 % CI = −1.4 to −.1 ; d = −.52 , p = .020 ) , despite family responsibilities ( −1.0 ; 95 % CI = −1.7 to −.3 ; d = −.62 , p = .005 ) and when PA is boring ( −.8 ; 95 % CI = −1.4 to −.1 ; d = −.54 , p = .016 ) . Conclusion : UCAN had negative effects on motivational variables in cancer survivors . These findings may be explained by method ological issues related to measuring motivation and /or the absence of post-intentional constructs Background Physical activity ( PA ) is beneficial in improving negative physical and psychological effects of cancer and cancer treatment , but adherence to PA guidelines is low . Computer-tailored PA interventions can reach large population s with little re sources . They match with patients ’ preference for home-based , unsupervised PA programs and are thus promising for the growing population of cancer survivors . The current study assessed the efficacy of a computer-tailored PA intervention in ( four subgroups of ) prostate and colorectal cancer survivors . Methods Prostate and colorectal cancer patients and survivors were r and omized to the OncoActive intervention group ( N = 249 ) , or a usual-care waiting-list control group ( N = 229 ) . OncoActive participants received a pedometer and computer-tailored PA advice , both Web-based via an interactive website and with printed material s. Minutes moderate-to-vigorous PA ( MVPA ) and days ≥30 min PA were assessed with an accelerometer ( ActiGraph ) at baseline and 6 months . Further , question naires were used to assess self-reported PA , fatigue , distress , and quality of life at baseline , 3 and 6 months . Differences between both groups were assessed using linear regression analyses ( complete cases and intention-to-treat ) . In addition , efficacy in relation to age , gender , education , type of cancer , and time since treatment was examined . Results Three months after baseline OncoActive participants significantly increased their self-reported PA ( PA days : d = 0.46 ; MVPA : d = 0.23 ) . Physical functioning ( d = 0.23 ) and fatigue ( d = − 0.21 ) also improved significantly after three months . Six months after baseline , self-reported PA ( PA days : d = 0.51 ; MVPA : d = 0.37 ) and ActiGraph MVPA ( d = 0.27 ) increased significantly , and ActiGraph days ( d = 0.16 ) increased borderline significantly ( p = .05 ; d = 0.16 ) . Furthermore , OncoActive participants reported significantly improvements in physical functioning ( d = 0.14 ) , fatigue ( d = − 0.23 ) and depression ( d = − 0.32 ) . Similar results were found for intention-to-treat analyses . Higher increases in PA were found for colorectal cancer participants at 3 months , and for medium and highly educated participants ’ PA at 6 months . Health outcomes at 6 months were more prominent in colorectal cancer participants and in women . Conclusions The OncoActive intervention was effective at increasing PA in prostate and colorectal cancer patients and survivors . Health-related effects were especially apparent in colorectal cancer participants . The intervention provides opportunities to accelerate cancer recovery . Long-term follow-up should examine further sustainability of these effects . Trial registration The study was registered in the Dutch Trial Register ( NTR4296 ) on October 17 2018 Background Physical activity ( PA ) can improve a range of outcomes following a cancer diagnosis . These include an improvement in experience of side effects of treatment ( eg , fatigue ) and management of comorbid conditions . PA might also increase survival and reduce recurrence . Digital interventions have shown potential for PA promotion among cancer survivors , but most in a previous review were Web-based , and few studies used mobile apps . There are many PA apps available for general public use , but it is unclear whether these are suitable as a PA intervention after a cancer diagnosis . Objective This study sought posttreatment nonmetastatic breast , prostate , and colorectal cancer survivors ’ opinions of using smartphone apps to promote PA and gathered their views on existing publicly available PA apps to inform a future intervention . Methods Each participant was r and omly assigned to download 2 of 4 apps ( Human , The Walk , The Johnson & Johnson Official 7 Minute Workout , and Gorilla Workout ) . Participants used each app for 1 week consecutively . In-depth semistructured telephone interviews were then conducted to underst and participants ’ experiences of using the apps and how app-based PA interventions could be developed for cancer survivors . The interviews were analyzed using thematic analysis . Results Thirty-two participants took part : 50 % ( 16/32 ) had prostate cancer , 25 % ( 8/32 ) had breast cancer , and 25 % ( 8/32 ) had colorectal cancer . Three core themes were identified . The first theme was that multiple factors affect engagement with PA apps and this is highly personalized . Factors affecting engagement included participants ’ perceptions of ( 1 ) the advantages and disadvantages of using apps to support PA , ( 2 ) the relevance of the app to the user ( eg , in terms of cancer-related factors , their PA goals , the difficulty level of the app , the way in which they interact with their mobile phone , and the extent to which the app fits with their self-identity ) , ( 3 ) the quality of the app ( eg , usability , accuracy , quality of production , and scientific evidence -base ) , and ( 4 ) the behavior change techniques used to promote PA . In the second theme , participants recommended that apps that promote walking are most appealing , as walking removes many barriers to PA . Finally , the participants suggested that PA apps should be integrated into cancer care , as they valued guidance and recommendations from health care professionals . Conclusions This sample of breast , prostate , and colorectal cancer survivors was receptive to the use of apps to promote PA . Although no publicly available PA app was deemed wholly suitable , many suggestions for adaptation and intervention development were provided . The results can inform the development of an app-based PA intervention for cancer survivors . They also highlight the wide-ranging and dynamic influences on engagement with digital interventions , which can be applied to other evaluations of mobile health products in other health conditions and other health behaviors |
716 | 28,187,752 | Conclusions The principal finding of this meta- analysis is that after adjusting for confounders , there is insufficient evidence to associate targeting urine output with an effect on 30-day mortality . | Background Oliguria is associated with a decreased kidney- and organ perfusion , leading to organ damage and increased mortality .
While the effects of correcting oliguria on renal outcome have been investigated frequently , whether urine output is a modifiable risk factor for mortality or simply an epiphenomenon remains unclear .
We investigated whether targeting urine output , defined as achieving and maintaining urine output above a predefined threshold , in hemodynamic management protocol s affects 30-day mortality in perioperative and critical care . | Introduction Perioperative goal -directed therapy ( PGDT ) may improve postoperative outcome in high-risk surgery patients but its adoption has been slow . In 2012 , we initiated a performance improvement ( PI ) project focusing on the implementation of PGDT during high-risk abdominal surgeries . The objective of the present study was to evaluate the effectiveness of this intervention . Methods This is a historical prospect i ve quality improvement study . The goal of this initiative was to st and ardize the way fluid management and hemodynamic optimization are conducted during high-risk abdominal surgery in the Departments of Anesthesiology and Surgery at the University of California Irvine . For fluid management , the protocol consisted in st and ardized baseline crystalloid administration of 3 ml/kg/hour and any additional boluses based on PGDT . The impact of the intervention was assessed on the length of stay in the hospital ( LOS ) and post-operative complications ( NSQIP data base ) . Results In the 1 year pre- and post-implementation periods , 128 and 202 patients were included . The average volume of fluid administered during the case was 9.9 ( 7.1–13.0 ) ml/kg/hour in the pre-implementation period and 6.6 ( 4.7–9.5 ) ml/kg/hour in the post-implementation period ( p < 0.01 ) . LOS decreased from 10 ( 6–16 ) days to 7 ( 5–11 ) days ( p = 0.0001 ) . Based on the multiple linear regression analysis , the estimated coefficient for intervention was 0.203 ( SE = 0.054 , p = 0.0002 ) indicating that , with the other conditions being held the same , introducing intervention reduced LOS by 18 % ( 95 % confidence interval 9–27 % ) . The incidence of NSQIP complications decreased from 39 % to 25 % ( p = 0.04 ) . Conclusion These results suggest that the implementation of a PI program focusing on the implementation of PGDT can transform fluid administration patterns and improve postoperative outcome in patients undergoing high-risk abdominal surgeries . Trial registration Clinical trials.gov NCT02057653 . Registered 17 December 2013 Introduction Several studies have shown that goal -directed hemodynamic and fluid optimization may result in improved outcome . However , the methods used were either invasive or had other limitations . The aim of this study was to perform intraoperative goal -directed therapy with a minimally invasive , easy to use device ( FloTrac/Vigileo ) , and to evaluate possible improvements in patient outcome determined by the duration of hospital stay and the incidence of complications compared to a st and ard management protocol . Methods In this r and omized , controlled trial 60 high-risk patients scheduled for major abdominal surgery were included . Patients were allocated into either an enhanced hemodynamic monitoring group using a cardiac index based intraoperative optimization protocol ( FloTrac/Vigileo device , GDT-group , n = 30 ) or a st and ard management group ( Control-group , n = 30 ) , based on st and ard monitoring data . Results The median duration of hospital stay was significantly reduced in the GDT-group with 15 ( 12 - 17.75 ) days versus 19 ( 14 - 23.5 ) days ( P = 0.006 ) and fewer patients developed complications than in the Control-group [ 6 patients ( 20 % ) versus 15 patients ( 50 % ) , P = 0.03 ] . The total number of complications was reduced in the GDT-group ( 17 versus 49 complications , P = 0.001 ) . Conclusions In high-risk patients undergoing major abdominal surgery , implementation of an intraoperative goal -directed hemodynamic optimization protocol using the FloTrac/Vigileo device was associated with a reduced length of hospital stay and a lower incidence of complications compared to a st and ard management protocol .Trial Registration Clinical trial registration information : Unique identifier : BACKGROUND In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock , mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal -directed therapy ( EGDT ) , in which intravenous fluids , vasopressors , inotropes , and blood transfusions were adjusted to reach central hemodynamic targets , than among those receiving usual care . We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary . METHODS In 31 emergency departments in the United States , we r and omly assigned patients with septic shock to one of three groups for 6 hours of resuscitation : protocol -based EGDT ; protocol -based st and ard therapy that did not require the placement of a central venous catheter , administration of inotropes , or blood transfusions ; or usual care . The primary end point was 60-day in-hospital mortality . We tested sequentially whether protocol -based care ( EGDT and st and ard-therapy groups combined ) was superior to usual care and whether protocol -based EGDT was superior to protocol -based st and ard therapy . Secondary outcomes included longer-term mortality and the need for organ support . RESULTS We enrolled 1341 patients , of whom 439 were r and omly assigned to protocol -based EGDT , 446 to protocol -based st and ard therapy , and 456 to usual care . Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids , vasopressors , inotropes , and blood transfusions . By 60 days , there were 92 deaths in the protocol -based EGDT group ( 21.0 % ) , 81 in the protocol -based st and ard-therapy group ( 18.2 % ) , and 86 in the usual-care group ( 18.9 % ) ( relative risk with protocol -based therapy vs. usual care , 1.04 ; 95 % confidence interval [ CI ] , 0.82 to 1.31 ; P=0.83 ; relative risk with protocol -based EGDT vs. protocol -based st and ard therapy , 1.15 ; 95 % CI , 0.88 to 1.51 ; P=0.31 ) . There were no significant differences in 90-day mortality , 1-year mortality , or the need for organ support . CONCLUSIONS In a multicenter trial conducted in the tertiary care setting , protocol -based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes . ( Funded by the National Institute of General Medical Sciences ; ProCESS Clinical Trials.gov number , NCT00510835 . ) BACKGROUND Patients with proximal femoral fracture ( PFF ) are at high risk of postoperative complications . Goal -directed haemodynamic treatment ( GDHT ) in other high-risk surgical patients reduces postoperative complications . We aim ed to compare effects of GDHT and routine fluid treatment ( RFT ) on postoperative outcomes after PFF surgery . METHODS PFF patients ( ≥70 yr ) were enrolled in this single-centre , open , r and omized , controlled , parallel-group superiority trial with concealed allocation using computer-generated r and omization . TREATMENTS ( i ) GDHT to attain oxygen delivery index > 600 ml min(-1 ) m(-2 ) using fluids and dobutamine and ( ii ) a protocol -guided RFT . After 150 enrolled patients , the trial was stopped due to slow recruitment . The short-term primary outcome measure was the relative risk ( RR ) of postoperative complications ; secondary measures were ( i ) administered fluid levels , ( ii ) vasopressor requirements , and ( iii ) haemodynamic responses . RESULTS For the GDHT group , 74 and for the RFT group 75 patients were design ated . The RR of postoperative complications ( GDHT vs RFT ) was 0.79 ( 95 % confidence interval 0.54 - 1.16 ) ; the volumes of i.v . fluids decreased ( 1078 vs 1440 ml , P=0.01 ) ; fewer patients required treatment of hypotension ( 18.5 % vs 75 % , P<0.005 ) ; there were more patients with increased oxygen delivery at the end of operation ( 28 % vs 8 % , P=0.04 ) , but the haemodynamic goal was achieved in only 27 % of patients in the GDHT group . CONCLUSIONS The magnitude of risk reduction of postoperative complications is clinical ly relevant , but the trial was underpowered and the null hypothesis can not be rejected Background Our aim was to determine whether substitution of goal -directed fluid therapy ( GDT ) ( perioperative fluid administration ) for traditional therapy to manage elderly patients with coronary heart disease scheduled for gastrointestinal ( GI ) surgery was advantageous . We determined if it would reduce cardiac complications and shorten time to recovery and discharge . Methods Altogether , 60 of these elderly patients were r and omized into GDT ( n = 30 ) and control ( n = 30 ) groups . In the GDT group , fluid management was carried out under guidance of hemodynamic status indicators . Types and quantities of fluids administered , blood loss , intraoperative urine output , time of extubation , intensive care unit ( ICU ) stay , hospital stay , postoperative adverse cardiac events , and GI complications were recorded . Results Total fluids infused were 2,910 ± 645 ml ( GDT group ) and 3,640 ± 771 ml ( control group ) ( p < 0.05 ) . Numbers of adverse cardiac events in the two groups were not significantly different ( p = 0.121 ) . Return of GI function was significantly faster in the GDT group ( p < 0.001 ) . Median ICU stay was 32.5 h in the GDT group and 47.5 h in the control group ( p < 0.001 ) . Median hospital stay was 18 days in the GDT group and 22 days in the control group ( p < 0.001 ) . Conclusions GDT was associated with shorter ICU stay and time to discharge and faster return of GI function compared to traditional fluid therapy . The number of adverse cardiac events was similar in the two groups Introduction Total hip replacement is one of the most commonly performed major orthopaedic operations . Goal -directed therapy ( GDT ) using haemodynamic monitoring has previously demonstrated outcome benefits in high-risk surgical patients under general anaesthesia . GDT has never been formally assessed during regional anaesthesia . Methods Patients undergoing total hip replacement while under regional anaesthesia were r and omised to either the control group ( CTRL ) or the protocol group ( GDT ) . Patients in the GDT group , in addition to st and ard monitoring , were connected to the FloTrac sensor/Vigileo monitor haemodynamic monitoring system , and a GDT protocol was used to maximise the stroke volume and target the oxygen delivery index to > 600 mL/minute/m2 . Results Patients r and omised to the GDT group were given a greater volume of intravenous fluids during the intraoperative period ( means ± st and ard deviation ( SD ) : 6,032 ± 1,388 mL vs. 2,635 ± 346 mL ; P < 0.0001 ) , and more of the GDT patients received dobutamine ( 0 of 20 CTRL patients vs. 11 of 20 GDT patients ; P < 0.0003 ) . The GDT patients also received more blood transfused during the intraoperative period ( means ± SD : 595 ± 316 mL vs. 0 ± 0 mL ; P < 0.0001 ) , although the CTRL group received greater volumes of blood replacement postoperatively ( CTRL patients 658 ± 68 mL vs. GDT patients 198 ± 292 mL ; P < 0.001 ) . Overall blood consumption ( intraoperatively and postoperatively ) was not different between the two groups . There were an increased number of complications in the CTRL group ( 20 of 20 CTRL patients ( 100 % ) vs. 16 of 20 GDT patients ( 80 % ) ; P = 0.05 ) . These outcomes were predominantly due to a difference in minor complications ( 20 of 20 CTRL patients ( 100 % ) vs. 15 of 20 GDT patients ( 75 % ) ; P = 0.047 ) . Conclusions GDT applied during regional anaesthesia in patients undergoing elective total hip replacement changes intraoperative fluid management and may improve patient outcomes by decreasing postoperative complications . Larger trials are required to confirm our findings .Trial registration S RCT Organ dysfunction and multiple organ failure are the main causes of prolonged hospital stay after cardiac surgery , which increases re source use and health care costs . Increased levels of oxygen delivery and consumption are associated with improved outcome in different groups of postoperative patients . Cardiac surgical patients are at risk of inadequate perioperative oxygen delivery caused by extracorporeal circulation and limited cardiovascular reserves . The purpose of our study was to test whether increasing oxygen delivery immediately after cardiac surgery would shorten hospital and intensive care unit ( ICU ) stay . Four hundred three elective cardiac surgical patients were enrolled in the study and r and omly assigned to either the control or the protocol group . Goals of the protocol group were to maintain Svo2 > 70 % and lactate concentration ≤2.0 mmol/L from admission to the ICU and up to 8 h thereafter . Hemodynamics , oxygen transport data , and organ dysfunctions were recorded . The median hos-pital stay was shorter in the protocol group ( 6 vs 7 days , P < 0.05 ) , and patients were discharged faster from the hospital than those in the control group ( P < 0.05 ) . Discharge from the ICU was similar between groups ( P = 0.8 ) . Morbidity was less frequent at the time of hospital discharge in the protocol group ( 1.1 % vs 6.1 % , P < 0.01 ) . Increasing oxygen delivery to achieve normal Svo2 values and lactate concentration during the immediate postoperative period after cardiac surgery can shorten the length of hospital stay . Implication s Health care economics has challenged clinicians to reduce costs and improve re source use in cardiac surgery and anesthesia in a patient population increasing in age and in severity of disease . Optimizing cardiovascular function to maintain adequate oxygen delivery during the immediate postoperative period after cardiac surgery can decrease morbidity and reduce length of hospital stay Introduction Post-operative outcomes may be improved by the use of flow related end-points for intra-venous fluid and /or low dose inotropic therapy . The mechanisms underlying this benefit remain uncertain . The objective of this study was to assess the effects of stroke volume guided intra-venous fluid and low dose dopexamine on tissue microvascular flow and oxygenation and inflammatory markers in patients undergoing major gastrointestinal surgery . Methods R and omised , controlled , single blind study of patients admitted to a university hospital critical care unit following major gastrointestinal surgery . For eight hours after surgery , intra-venous fluid therapy was guided by measurements of central venous pressure ( CVP group ) , or stroke volume ( SV group ) . In a third group stroke volume guided fluid therapy was combined with dopexamine ( 0.5 mcg/kg/min ) ( SV & DPX group ) . Results 135 patients were recruited ( n = 45 per group ) . In the SV & DPX group , increased global oxygen delivery was associated with improved sublingual ( P < 0.05 ) and cutaneous microvascular flow ( P < 0.005 ) ( sublingual microscopy and laser Doppler flowmetry ) . Microvascular flow remained constant in the SV group but deteriorated in the CVP group ( P < 0.05 ) . Cutaneous tissue oxygen partial pressure ( PtO2 ) ( Clark electrode ) improved only in the SV & DPX group ( P < 0.001 ) . There were no differences in serum inflammatory markers . There were no differences in overall complication rates between the groups although acute kidney injury was more frequent in the CVP group ( CVP group ten patients ( 22 % ) ; pooled SV and SV & DPX groups seven patients ( 8 % ) ; P = 0.03 ) ( post hoc analysis ) . Conclusions Stroke volume guided fluid and low dose inotropic therapy was associated with improved global oxygen delivery , microvascular flow and tissue oxygenation but no differences in the inflammatory response to surgery . These observations may explain improved clinical outcomes associated with this treatment in previous trials . Trial registration numberIS RCT N BACKGROUND Early goal -directed therapy ( EGDT ) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock . However , its effectiveness is uncertain . METHODS In this trial conducted at 51 centers ( mostly in Australia or New Zeal and ) , we r and omly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care . The primary outcome was all-cause mortality within 90 days after r and omization . RESULTS Of the 1600 enrolled patients , 796 were assigned to the EGDT group and 804 to the usual-care group . Primary outcome data were available for more than 99 % of the patients . Patients in the EGDT group received a larger mean ( ±SD ) volume of intravenous fluids in the first 6 hours after r and omization than did those in the usual-care group ( 1964±1415 ml vs. 1713±1401 ml ) and were more likely to receive vasopressor infusions ( 66.6 % vs. 57.8 % ) , red-cell transfusions ( 13.6 % vs. 7.0 % ) , and dobutamine ( 15.4 % vs. 2.6 % ) ( P<0.001 for all comparisons ) . At 90 days after r and omization , 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group , for rates of death of 18.6 % and 18.8 % , respectively ( absolute risk difference with EGDT vs. usual care , -0.3 percentage points ; 95 % confidence interval , -4.1 to 3.6 ; P=0.90 ) . There was no significant difference in survival time , in-hospital mortality , duration of organ support , or length of hospital stay . CONCLUSIONS In critically ill patients presenting to the emergency department with early septic shock , EGDT did not reduce all-cause mortality at 90 days . ( Funded by the National Health and Medical Research Council of Australia and the Alfred Foundation ; ARISE Clinical Trials.gov number , NCT00975793 . ) BACKGROUND Early , goal -directed therapy ( EGDT ) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock . However , adoption has been limited , and uncertainty about its effectiveness remains . METHODS We conducted a pragmatic r and omized trial with an integrated cost-effectiveness analysis in 56 hospitals in Engl and . Patients were r and omly assigned to receive either EGDT ( a 6-hour resuscitation protocol ) or usual care . The primary clinical outcome was all-cause mortality at 90 days . RESULTS We enrolled 1260 patients , with 630 assigned to EGDT and 630 to usual care . By 90 days , 184 of 623 patients ( 29.5 % ) in the EGDT group and 181 of 620 patients ( 29.2 % ) in the usual-care group had died ( relative risk in the EGDT group , 1.01 ; 95 % confidence interval [ CI ] , 0.85 to 1.20 ; P=0.90 ) , for an absolute risk reduction in the EGDT group of -0.3 percentage points ( 95 % CI , -5.4 to 4.7 ) . Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids , vasoactive drugs , and red-cell transfusions and reflected by significantly worse organ-failure scores , more days receiving advanced cardiovascular support , and longer stays in the intensive care unit . There were no significant differences in any other secondary outcomes , including health-related quality of life , or in rates of serious adverse events . On average , EGDT increased costs , and the probability that it was cost-effective was below 20 % . CONCLUSIONS In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation , hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome . ( Funded by the United Kingdom National Institute for Health Research Health Technology Assessment Programme ; ProMISe Current Controlled Trials number , IS RCT N36307479 . ) Objective : To evaluate the influence of stroke volume variation (SVV)-based goal -directed therapy ( GDT ) on splanchnic organ functions and postoperative complications in orthopedic patients . Subjects and Methods : Eighty patients scheduled for major orthopedic surgery under general anesthesia were r and omly allocated to one of two equal groups to receive either intraoperative volume therapy guided by SVV ( GDT ) or st and ard fluid management ( control ) . In the SVV group , patients received colloid boluses of 4 ml/kg to maintain an SVV < 10 % when in the supine position or an SVV < 14 % if prone . In the control group , fluids were given to maintain a mean arterial pressure > 65 mm Hg , a heart rate < 100 bpm , a central venous pressure of 8 - 14 mm Hg , and a urine output > 0.5 ml/kg/h . Intraoperative organ perfusion , hemodynamic data , hospitalization , postoperative complications , and mortality were recorded . Results : The heart rate at the end of surgery was significantly lower ( p < 0.05 ) , there were fewer hypotensive episodes ( p < 0.05 ) , the arterial and gastric intramucosal pH were higher ( p < 0.05 for both ) , the gastric intramucosal PCO2 was lower ( p < 0.05 ) , the intraoperative infused colloids and the total infused volume were lower ( p < 0.05 for both ) , and the postoperative time to flatus was shorter ( p < 0.05 ) in the GDT group than in the control group . No differences in the length of hospital stay , complications , or mortality were found between the groups . Conclusion : SVV-based GDT during major orthopedic surgery reduced the volume of the required intraoperative infused fluids , maintained intraoperative hemodynamic stability , and improved the perioperative gastrointestinal function Objective To compare intrathoracic blood volume ( ITBV ) guided fluid management and central venous pressure ( CVP ) guided therapy in ameliorating the progression of early systemic inflammatory response in patients undergoing major surgery . Design Prospect i ve , r and omized clinical trial . Patients Forty patients undergoing major abdominal surgery were r and omized into CVP and ITBV groups . Interventions In the CVP group the target CVP was 8–12 mmHg while in the ITBV group the goal was to keep the ITBV between 850 and 950 ml/m2 during the operation . Measurements and results Hemodynamic parameters were determined by single arterial thermodilution . Measurements were repeated every 30 min intraoperatively . Serum procalcitonin ( PCT ) and C-reactive protein ( CRP ) was monitored preoperatively , on ICU admission , and then daily for 3 days . Serum TNF-α levels were measured intraoperatively hourly and then daily for 3 days . There was no significant difference between the two groups regarding hemodynamic parameters at any assessment point . In the overall population changes in the stroke volume index showed a significant correlation with changes in CVP and ITBV . TNF-α levels remained in the normal range intraoperatively and during the three postoperative days in both groups . Preoperatively normal PCT and CRP levels increased significantly postoperatively , without significant differences between the groups . Conclusions ITBV guided fluid therapy did not alter the magnitude of inflammatory response as monitored by serum PCT , CRP , and TNF-α in the early postoperative period Objective To evaluate the effects of maximizing the oxygen delivery on morbidity and mortality in patients > 60 yrs of age and /or with chronic diseases of vital organs who underwent major elective surgery . Design Prospect i ve , r and omized , controlled trial . Setting A 24-bed general intensive care unit of a teaching hospital . Patients Thirty-seven high-risk patients who underwent major surgery . Interventions The hemodynamic and oxygen transport variables and outcomes in 18 patients ( control group ) treated to maintain normal values of oxygen delivery were compared with 19 patients ( protocol group ) treated to maintain “ supranormal ” values . Therapy in both groups consisted of volume expansion and , when necessary , dobutamine to reach target values , during the surgery and 24 hrs postoperatively . Measurements and Main Results We interrupted the study because of a significant difference in the 60-day mortality rate . The mortality rate in the control group was significantly higher when compared with the protocol group ( 9/18 [ 50 % ] vs. 3/19 [ 15.7 % ] , p < .05 ) . The prevalence of clinical and infectious complications was higher in the control group than in the protocol group ( 67 % and 31 % respectively ; relative risk , 0.47 ; 95 % confidence interval , 0.226–0.991;p < .05 ) and there was a trend toward more severe organ dysfunction in nonachievers patients ( 17/24 [ 71 % ] vs. 6/13 [ 46 % ] , relative risk , 0.65 ; 95 % confidence interval , 0.343–1.237 ; NS ) . Conclusion Older patients with existing cardiorespiratory illness undergoing major surgery have a reduced morbidity and mortality when dobutamine is used to maximize oxygen transport Background : The authors investigated the incidence and risk factors for postoperative acute renal failure after major noncardiac surgery among patients with previously normal renal function . Methods : Adult patients undergoing major noncardiac surgery with a preoperative calculated creatinine clearance of 80 ml/min or greater were included in a prospect i ve , observational study at a single tertiary care university hospital . Patients were followed for the development of acute renal failure ( defined as a calculated creatinine clearance of 50 ml/min or less ) within the first 7 postoperative days . Patient preoperative characteristics and intraoperative anesthetic management were evaluated for associations with acute renal failure . Thirty-day , 60-day , and 1-yr all-cause mortality was also evaluated . Results : A total of 65,043 cases between 2003 and 2006 were review ed . Of these , 15,102 patients met the inclusion criteria ; 121 patients developed acute renal failure ( 0.8 % ) , and 14 required renal replacement therapy ( 0.1 % ) . Seven independent preoperative predictors were identified ( P < 0.05 ) : age , emergent surgery , liver disease , body mass index , high-risk surgery , peripheral vascular occlusive disease , and chronic obstructive pulmonary disease necessitating chronic bronchodilator therapy . Several intraoperative management variables were independent predictors of acute renal failure : total vasopressor dose administered , use of a vasopressor infusion , and diuretic administration . Acute renal failure was associated with increased 30-day , 60-day , and 1-yr all-cause mortality . Conclusions : Several preoperative predictors previously reported to be associated with acute renal failure after cardiac surgery were also found to be associated with acute renal failure after noncardiac surgery . The use of vasopressor and diuretics is also associated with acute renal failure Introduction Stroke volume variation ( SVV ) is a good and easily obtainable predictor of fluid responsiveness , which can be used to guide fluid therapy in mechanically ventilated patients . During major abdominal surgery , inappropriate fluid management may result in occult organ hypoperfusion or fluid overload in patients with compromised cardiovascular reserves and thus increase postoperative morbidity . The aim of our study was to evaluate the influence of SVV guided fluid optimization on organ functions and postoperative morbidity in high risk patients undergoing major abdominal surgery . Methods Patients undergoing elective intraabdominal surgery were r and omly assigned to a Control group ( n = 60 ) with routine intraoperative care and a Vigileo group ( n = 60 ) , where fluid management was guided by SVV ( Vigileo/FloTrac system ) . The aim was to maintain the SVV below 10 % using colloid boluses of 3 ml/kg . The laboratory parameters of organ hypoperfusion in perioperative period , the number of infectious and organ complications on day 30 after the operation , and the hospital and ICU length of stay and mortality were evaluated . The local ethics committee approved the study . Results The patients in the Vigileo group received more colloid ( 1425 ml [ 1000 - 1500 ] vs. 1000 ml [ 540 - 1250 ] ; P = 0.0028 ) intraoperatively and a lower number of hypotensive events were observed ( 2[1 - 2 ] Vigileo vs. 3.5[2 - 6 ] in Control ; P = 0.0001 ) . Lactate levels at the end of surgery were lower in Vigileo ( 1.78 ± 0.83 mmol/l vs. 2.25 ± 1.12 mmol/l ; P = 0.0252 ) . Fewer Vigileo patients developed complications ( 18 ( 30 % ) vs. 35 ( 58.3 % ) patients ; P = 0.0033 ) and the overall number of complications was also reduced ( 34 vs. 77 complications in Vigileo and Control respectively ; P = 0.0066 ) . A difference in hospital length of stay was found only in per protocol analysis of patients receiving optimization ( 9 [ 8 - 12 ] vs. 10 [ 8 - 19 ] days ; P = 0.0421 ) . No difference in mortality ( 1 ( 1.7 % ) vs. 2 ( 3.3 % ) ; P = 1.0 ) and ICU length of stay ( 3 [ 2 - 5 ] vs. 3 [ 0.5 - 5 ] ; P = 0.789 ) was found . Conclusions In this study , fluid optimization guided by SVV during major abdominal surgery is associated with better intraoperative hemodynamic stability , decrease in serum lactate at the end of surgery and lower incidence of postoperative organ complications . Trial registration Current Controlled Trials IS RCT N95085011 Introduction Esophageal Doppler was confirmed as a useful non-invasive tool for management of fluid replacement in elective surgery . The aim of this study was to assess the effect of early optimization of intravascular volume using esophageal Doppler on blood lactate levels and organ dysfunction development in comparison with st and ard hemodynamic management in multiple-trauma patients . Methods This was a r and omized controlled trial . Multiple-trauma patients with blood loss of more than 2,000 ml admitted to the intensive care unit ( ICU ) were r and omly assigned to the protocol group with esophageal Doppler monitoring and to the control group . Fluid resuscitation in the Doppler group was guided for the first 12 hours of ICU stay according to the protocol based on data obtained by esophageal Doppler , whereas control patients were managed conventionally . Blood lactate levels and organ dysfunction during ICU stay were evaluated . Results Eighty patients were r and omly assigned to Doppler and 82 patients to control treatment . The Doppler group received more intravenous colloid during the first 12 hours of ICU stay ( 1,667 ± 426 ml versus 682 ± 322 ml ; p < 0.0001 ) , and blood lactate levels in the Doppler group were lower after 12 and 24 hours of treatment than in the control group ( 2.92 ± 0.54 mmol/l versus 3.23 ± 0.54 mmol/l [ p = 0.0003 ] and 1.99 ± 0.44 mmol/l versus 2.37 ± 0.58 mmol/l [ p < 0.0001 ] , respectively ) . No difference in organ dysfunction between the groups was found . Fewer patients in the Doppler group developed infectious complications ( 15 [ 18.8 % ] versus 28 [ 34.1 % ] ; relative risk = 0.5491 ; 95 % confidence interval = 0.3180 to 0.9482 ; p = 0.032 ) . ICU stay in the Doppler group was reduced from a median of 8.5 days ( interquartile range [ IQR ] 6 to16 ) to 7 days ( IQR 6 to 11 ) ( p = 0.031 ) , and hospital stay was decreased from a median of 17.5 days ( IQR 11 to 29 ) to 14 days ( IQR 8.25 to 21 ) ( p = 0.045 ) . No significant difference in ICU and hospital mortalities between the groups was found . Conclusion Optimization of intravascular volume using esophageal Doppler in multiple-trauma patients is associated with a decrease of blood lactate levels , a lower incidence of infectious complications , and a reduced duration of ICU and hospital stays Aims : To report the use of transesophageal Doppler ( TED ) , a minimally invasive cardiac output ( COP ) monitor , before , during and after reperfusion and study its effect on anesthetic management during living donor liver transplantation ( LDLT ) . Setting and Design : A prospect i ve observational study . Methods : A total of 25 consecutive recipients with a MELD score between 15 and 20 were enrolled . Data were recorded at baseline ( TB ) ; anhepatic phase ( TA ) ; and post-reperfusion — 1 , 5 , 10 and 30 minutes . Fluid therapy was guided by corrected flow time ( FTc ) of the TED . Packed red blood cells ( RBCs ) were only given when hematocrit was less than 25 % . Rotational thromboelastometry ( ROTEM ) and st and ard laboratory tests were used to guide component blood products requirements . Results : Post-reperfusion , the COP , Cardiac Index ( CI ) and stroke volume ( SV ) increased significantly at all points of measurements ; this was associated with a significant decrease in systemic vascular resistance ( SVR ) ( P ; < .05 ) . Immediately post-reperfusion , for 5 minutes , mean arterial blood pressure ( ABP ) dropped significantly ( P < .05 ) , and 14 out of the 25 patients required boluses of epinephrine ( 10 μg ) to restore the mean ABP ; 3 of the 14 patients required norepinephrine infusion till the end of surgery . Central venous pressure ( CVP ) and urine output ( UOP ) at all measures were maintained adequately with FTc-guided fluid replacement . Eight out of the 25 patients required no blood transfusion , and 4 of the 8 patients required no catecholamine support . Conclusion : TED as a sole monitor for COP was able to present significant and reliable changes in the cardiovascular status of the recipients during reperfusion , which could help to guide fluid- and drug-supportive therapy in this population of patients . This preliminary study needs to be applied on a larger scale Abstract Objective To assess whether a nurse led , flow monitored protocol for optimising circulatory status in patients after cardiac surgery reduces complications and shortens stay in intensive care and hospital . Design R and omised controlled trial . Setting Intensive care unit and cardiothoracic unit of a university teaching hospital . Participants 174 patients who underwent cardiac surgery between April 2000 and January 2003 . Interventions Patients were allocated to conventional haemodynamic management or to an algorithm guided by oesophageal Doppler flowmetry to maintain a stroke index above 35 ml/m2 . Results 26 control patients had postoperative complications ( two deaths ) compared with 17 ( four deaths ) protocol patients ( P = 0.08 ) . Duration of hospital stay in the protocol group was significantly reduced from a median of nine ( interquartile range 7 - 12 ) days to seven ( 7 - 10 ) days ( P = 0.02 ) . The mean duration of hospital stay was reduced from 13.9 to 11.4 days , a saving in hospital bed days of 18 % ( 95 % confidence interval −12 % to 47 % ) . Usage of intensive care beds was reduced by 23 % ( −8 % to 59 % ) . Conclusion A nurse delivered protocol for optimising circulatory status in the early postoperative period after cardiac surgery may significantly shorten hospital stay Introduction In ICUs , both fluid overload and oliguria are common complications associated with increased mortality among critically ill patients , particularly in acute kidney injury ( AKI ) . Although fluid overload is an expected complication of oliguria , it remains unclear whether their effects on mortality are independent of each other . The aim of this study is to evaluate the impact of both fluid balance and urine volume on outcomes and determine whether they behave as independent predictors of mortality in adult ICU patients with AKI . Methods We performed a secondary analysis of data from a multicenter , prospect i ve cohort study in 10 Italian ICUs . AKI was defined by renal sequential organ failure assessment ( SOFA ) score ( creatinine > 3.5 mg/dL or urine output ( UO ) < 500 mL/d ) . Oliguria was defined as a UO < 500 mL/d . Mean fluid balance ( MFB ) and mean urine volume ( MUV ) were calculated as the arithmetic mean of all daily values . Use of diuretics was noted daily . To assess the impact of MFB and MUV on mortality of AKI patients , multivariate analysis was performed by Cox regression . Results Of the 601 included patients , 132 had AKI during their ICU stay and the mortality in this group was 50 % . Non-surviving AKI patients had higher MFB ( 1.31 ± 1.24 versus 0.17 ± 0.72 L/day ; P < 0.001 ) and lower MUV ( 1.28 ± 0.90 versus 2.35 ± 0.98 L/day ; P < 0.001 ) as compared to survivors . In the multivariate analysis , MFB ( adjusted hazard ratio ( HR ) 1.67 per L/day , 95%CI 1.33 to 2.09 ; < 0.001 ) and MUV ( adjusted HR 0.47 per L/day , 95%CI 0.33 to 0.67 ; < 0.001 ) remained independent risk factors for 28-day mortality after adjustment for age , gender , diabetes , hypertension , diuretic use , non-renal SOFA and sepsis . Diuretic use was associated with better survival in this population ( adjusted HR 0.25 , 95%CI 0.12 to 0.52 ; < 0.001 ) . Conclusions In this multicenter ICU study , a higher fluid balance and a lower urine volume were both important factors associated with 28-day mortality of AKI patients Background : The optimal amount and method for monitoring intravenous fluid in surgical patients is unresolved . Central venous oxygen saturation ( Scvo2 ) has been used to guide therapy and predict outcome in high-risk and intensive-care patients . The aim of this prospect i ve , r and omized trial was to compare the rate of postoperative complications in patients receiving fluid therapy guided by Scvo2 and those treated with a traditional effluent fluid scheme . Methods : Patients undergoing open colorectal and lower intestinal surgery ( n = 241 ) were r and omized to the Scvo2 group or the control group . The Scvo2 group received perioperatively crystalloid infusion 100 ml/h . When Scvo2 was less than 75 % , a bolus of 3 ml/kg hydroxyethyl starch was given . The bolus was repeated if Scvo2 increased by 1 percentage point or more . The control group was maintained with crystalloid 800 ml/h and given extra fluid if there were clinical signs of hypovolemia . The participating surgeon , unaware of the group allocation , registered complications within day 30 . Results : Until 8:00 am on the first postoperative day , the Scvo2 group had received 3,869 ± 992 ml ( mean ± SD ) intravenous fluid compared with 6,491 ± 1,649 ml in the control group . Increase in weight was 0.8 ± 1.8 kg and 2.5 ± 1.6 kg in the two groups , respectively . The postoperative complication rate was 42 % in both groups . Conclusion : Clinical outcomes among patients receiving Scvo2-guided perioperative fluid therapy were similar to those for patients treated with a traditional fluid regimen . Limitations in study design prevent full interpretation of these findings , and further large trials of this treatment algorithm are still required Introduction Goal -directed therapy ( GDT ) has been shown to improve outcome when commenced before surgery . This requires pre-operative admission to the intensive care unit ( ICU ) . In cardiac surgery , GDT has proved effective when commenced after surgery . The aim of this study was to evaluate the effect of post-operative GDT on the incidence of complications and duration of hospital stay in patients undergoing general surgery . Methods This was a r and omised controlled trial with concealed allocation . High-risk general surgical patients were allocated to post-operative GDT to attain an oxygen delivery index of 600 ml min-1 m-2 or to conventional management . Cardiac output was measured by lithium indicator dilution and pulse power analysis . Patients were followed up for 60 days . Results Sixty-two patients were r and omised to GDT and 60 patients to control treatment . The GDT group received more intravenous colloid ( 1,907 SD ± 878 ml versus 1,204 SD ± 898 ml ; p < 0.0001 ) and dopexamine ( 55 patients ( 89 % ) versus 1 patient ( 2 % ) ; p < 0.0001 ) . Fewer GDT patients developed complications ( 27 patients ( 44 % ) versus 41 patients ( 68 % ) ; p = 0.003 , relative risk 0.63 ; 95 % confidence intervals 0.46 to 0.87 ) . The number of complications per patient was also reduced ( 0.7 SD ± 0.9 per patient versus 1.5 SD ± 1.5 per patient ; p = 0.002 ) . The median duration of hospital stay in the GDT group was significantly reduced ( 11 days ( IQR 7 to 15 ) versus 14 days ( IQR 11 to 27 ) ; p = 0.001 ) . There was no significant difference in mortality ( seven patients ( 11.3 % ) versus nine patients ( 15 % ) ; p = 0.59 ) . Conclusion Post-operative GDT is associated with reductions in post-operative complications and duration of hospital stay . The beneficial effects of GDT may be achieved while avoiding the difficulties of pre-operative ICU admission BACKGROUND Occult hypovolaemia is a key factor in the aetiology of postoperative morbidity and may not be detected by routine heart rate and arterial pressure measurements . Intraoperative gut hypoperfusion during major surgery is associated with increased morbidity and postoperative hospital stay . We assessed whether using intraoperative oesophageal Doppler guided fluid management to minimize hypovolaemia would reduce postoperative hospital stay and the time before return of gut function after colorectal surgery . METHODS This single centre , blinded , prospect i ve controlled trial r and omized 128 consecutive consenting patients undergoing colorectal resection to oesophageal Doppler guided or central venous pressure (CVP)-based ( conventional ) intraoperative fluid management . The intervention group patients followed a dynamic oesophageal Doppler guided fluid protocol whereas control patients were managed using routine cardiovascular monitoring aim ing for a CVP between 12 and 15 mm Hg . RESULTS The median postoperative stay in the Doppler guided fluid group was 10 vs 11.5 days in the control group P<0.05 . The median time to resuming full diet in the Doppler guided fluid group was 6 vs 7 for controls P<0.001 . Doppler patients achieved significantly higher cardiac output , stroke volume , and oxygen delivery . Twenty-nine ( 45.3 % ) control patients suffered gastrointestinal morbidity compared with nine ( 14.1 % ) in the Doppler guided fluid group P<0.001 , overall morbidity was also significantly higher in the control group P=0.05 . CONCLUSIONS Intraoperative oesophageal Doppler guided fluid management was associated with a 1.5-day median reduction in postoperative hospital stay . Patients recovered gut function significantly faster and suffered significantly less gastrointestinal and overall morbidity BACKGROUND Hemodynamic therapy to raise the cardiac index and oxygen delivery to supranormal may improve outcomes in critically ill patients . We studied whether increasing the cardiac index to a supranormal level ( cardiac-index group ) or increasing mixed venous oxygen saturation to a normal level ( oxygen-saturation group ) would decrease morbidity and mortality among critically ill patients , as compared with a control group in which the target was a normal cardiac index . METHODS A total of 10,726 patients in 56 intensive care units were screened , among whom 762 patients belonging to predefined diagnostic categories with acute physiology scores of 11 or higher were r and omly assigned to the three groups ( 252 to the control group , 253 to the cardiac-index group , and 257 to the oxygen-saturation group ) . RESULTS The hemodynamic targets were reached by 94.3 percent of the control group , 44.9 percent of the cardiac-index group , and 66.7 percent of the oxygen-saturation group ( P < 0.001 ) . Mortality was 48.4 , 48.6 , and 52.1 percent , respectively ( P = 0.638 ) , up to the time of discharge from the intensive care unit and 62.3 , 61.7 , and 63.8 percent ( P = 0.875 ) at six months . Among patients who survived , the number of dysfunctional organs and the length of the stay in the intensive care unit were similar in the three groups . No differences in mortality among the three groups were found for any diagnostic category . A subgroup analysis of the patients in whom hemodynamic targets were reached revealed similar mortality rates : 44.8 , 40.4 , and 39.0 percent , respectively ( P = 0.478 ) . CONCLUSIONS Hemodynamic therapy aim ed at achieving supranormal values for the cardiac index or normal values for mixed venous oxygen saturation does not reduce morbidity or mortality among critically ill patients INTRODUCTION : No consensus exists regarding the optimal fluid ( crystalloid or colloid ) or strategy ( liberal , restricted , or goal directed ) for fluid management after colectomy . Prior assessment s have used normal saline . This is the first assessment of st and ard , goal -directed perioperative fluid management with either lactated Ringer ’s or hetastarch/lactated Ringer ’s , with use of esophageal Doppler for guidance , in laparoscopic colectomy with an enhanced recovery protocol . METHODS : A double-blinded , prospect i ve , r and omized , three-armed study with Institutional Review Board approval was used for patients undergoing laparoscopic segmental colectomy assigned to the st and ard , goal -directed/lactated Ringer ’s and goal -directed/hetastarch groups . A st and ard anesthesia and basal fluid administration protocol was used in addition to the goal -directed strategies guided by esophageal Doppler . RESULTS : Sixty-four patients undergoing laparoscopic colectomy ( 22 st and ard , 21 goal -directed/lactated Ringer ’s , 21 goal -directed/hetastarch ) had similar operative times ( st and ard , 2.3 hours ; goal -directed/lactated Ringer ’s , 2.5 hours ; goal -directed/hetastarch , 2.3 hours ) . The lactated Ringer ’s group received the greatest amount of total and milliliters per kilogram per hour of operative fluid ( st and ard , 2,850/18 ; goal -directed/lactated Ringer ’s , 3,800/23 ; and goal -directed/hetastarch , 3,300/17 ; P < 0.05 ) . The hetastarch group had the longest stay ( st and ard , 64.9 hours ; goal -directed/lactated Ringer ’s , 71.8 hours ; goal -directed/hetastarch , 75.5 hours ; P < 0.05 ) . The st and ard group received the greatest amount of fluid during hospitalization ( st and ard , 2.5 ml/kg/h ; goal -directed/lactated Ringer ’s , 1.9 ml/kg/h ; goal -directed/hetastarch , 2.1 ml/kg/h ; P < 0.05 ) . There was one instance of operative mortality in the goal -directed/hetastarch group . CONCLUSIONS : Goal -directed fluid management with a colloid/balanced salt solution offers no advantage and is more costly . However , goal -directed , individualized intraoperative fluid management with crystalloid should be evaluated further as a component of enhanced recovery protocol s following colectomy because of reduced overall fluid administration A r and omized controlled trial was conducted to test the hypothesis that there is no difference in complications in patients receiving intravenous ( iv ) water and electrolyte , based on either stroke volume or clinical indicators at bowel surgery BACKGROUND Increased perioperative fluid administration is an independent risk factor for lung injury after pulmonary resection . In clinical practice , fluid therapy is heavily guided by urinary output ; however , diuretic response to plasma volume expansion has been reported to be blunted during anesthesia and surgery . We therefore hypothesized that in patients undergoing video-assisted thoracoscopic surgery , different regimens of intraoperative fluid management would not affect urinary output as would be expected in the nonsurgical scenario . Moreover , a restrictive perioperative fluid approach , as indicated in these operations , will not harm renal function . METHODS One hundred two patients undergoing video-assisted thoracoscopic surgery were r and omly allocated to receive intraoperatively either high ( 8 mL/[kg · h ] ; n = 51 ) or low ( 2 mL/[kg · h ] ; n = 51 ) amounts of Ringer 's lactate solution . The primary end point was intraoperative urinary output . Secondary end points included postoperative creatinine serum levels and postoperative complication rate . RESULTS Demographic and surgical data were comparable between groups . Regardless of the intraoperatively fluids administered ( mean ± SD , 2131 ± 850 vs 1035 ± 652 mL in high and low groups , respectively ; P < .0001 ) , urinary output was similar ( median 300 mL ) . Perioperative creatinine serum levels decreased significantly postoperatively and were not significantly different among the groups . CONCLUSIONS In patients undergoing video-assisted thoracoscopic surgery , intraoperative urinary output and postoperative renal function are not affected by administration of fluids in the range of 2 to 8 mL/(kg · h ) . The clinical practice of administering fluids to enhance diuresis in the perioperative period should therefore be ab and oned Early goal -directed therapy is a term used to describe the guidance of intravenous fluid and vasopressor/inotropic therapy by using cardiac output or similar parameters in the immediate post-cardiopulmonary bypass in cardiac surgery patients . Early recognition and therapy during this period may result in better outcome . In keeping with this aim in the cardiac surgery patients , we conducted the present study . The study included 30 patients of both sexes , with EuroSCORE > or=3 undergoing coronary artery bypass surgery under cardiopulmonary bypass . The patients were r and omly divided into two groups , namely , control and early goal -directed therapy ( EGDT ) groups . All the subjects received st and ardized care ; arterial pressure was monitored through radial artery , central venous pressure through a triple lumen in the right internal jugular vein , electrocardiogram , oxygen saturation , temperature , urine output per hour and frequent arterial blood gas analysis . In addition , cardiac index monitoring using FloTrac and continuous central venous oxygen saturation using PreSep was used in patients in the EGTD group . Our aim was to maintain the cardiac index at 2.5 - 4.2 l/min/m2 , stroke volume index 30 - 65 ml/beat/m2 , systemic vascular resistance index 1500 - 2500 dynes/s/cm5/m2 , oxygen delivery index 450 - 600 ml/min/m2 , continuous central venous oximetry more than 70 % , stroke volume variation less than 10 % ; in addition to the control group parameters such as central venous pressure 6 - 8 mmHg , mean arterial pressure 90 - 105 mmHg , normal arterial blood gas analysis values , pulse oximetry , hematocrit value above 30 % and urine output more than 1 ml/kg/h . The aims were achieved by altering the administration of intravenous fluids and doses of inotropic or vasodilator agents . Three patients were excluded from the study and the data of 27 patients analyzed . The extra volume used ( 330+/-160 v/s 80+/-80 ml , P=0.043 ) number of adjustments of inotropic agents ( 3.4+/-1.5 v/s 0.4+/-0.7 , P=0.026 ) in the EGDT group were significant . The average duration of ventilation ( 13.8+/-3.2 v/s 20.7+/-7.1 h ) , days of use of inotropic agents ( 1.6+/-0.9 v/s 3.8+/-1.6 d ) , ICU stay ( 2.6+/-0.9 v/s 4.9+/-1.8 d ) and hospital stay ( 5.6+/-1.2 v/s 8.9+/-2.1 d ) were less in the EGDT group , compared to those in the control group . This study is inconclusive with regard to the beneficial aspects of the early goal -directed therapy in cardiac surgery patients , although a few benefits were observed BACKGROUND Our objective was to compare the effect of a restricted intravenous fluid regimen adjusted by serum lactate level with a st and ard restricted regimen on complications after major elective surgery for gastrointestinal malignancy . METHODS This is a r and omized , observer-blinded , single-center trial conducted across a time span of 13 months . A total of 299 patients were allocated to either a restricted intravenous fluid regimen with supplementary intravenous fluids given based on serum lactate level ( group A ) or a st and ard restricted regimen ( group R ) . In group A , the serum lactate level was monitored closely postoperatively to maintain a normal pre-operative serum lactate level . Group R involved patients treated with a restricted fluid regimen in whom additional fluid and electrolytes were administered when deemed necessary based on the usual clinical criteria . The primary outcome measure was complications ; the secondary measures were death and adverse effects . RESULTS Additional fluid supplementation was needed in some patients in both groups ( group A [ 28 % ] vs group R [ 26 % ] ) . In group A , the time for additional fluid infusion occurred earlier in the postoperative period than group R. Patients in group A received their first supplementary fluid treatment within the first 12 h more commonly than those in group R ( 74 % vs 37 % , respectively ; P < .004 ) . The regimen adjusted by serum lactate decreased systemic postoperative complications in group A versus group R ( 10 % vs 22 % , respectively ; P = .023 ) but not overall total complications ( 23 % vs 33 % , respectively ; P = .090 ) . In contrast , in patients who required additional fluid infusion , the difference in complications between the 2 groups was greater ( overall complication , 45 % vs 85 % , respectively ; P = .023 ; major complication , 16 % vs 44 % , respectively ; P = .018 ; systemic complications , 19 % vs 63 % , respectively ; P = .001 ) . One patient died in group A and 4 died in group R ( 1 % vs 4 % , respectively ; P = .206 ) . CONCLUSION A fluid-restricted regimen after elective gastrointestinal operations for malignancy may lead to fluid insufficiency and low tissue perfusion in up to 28 % of patients . Close monitoring of serum lactate levels with adjustment of intravenous fluid administration intraoperatively and in the early postoperative period may improve the early detection and correction of inadequate tissue perfusion , thereby decreasing the rate of complications OBJECTIVE The purpose of this study was to assess the effect of goal -directed therapy ( GDT ) , after cardiac surgery , on the incidence of acute kidney injury ( AKI ) . DESIGN This is a prospect i ve observational study design ed to achieve and maintain maximum stroke volume for 8 hours , in patients after cardiac surgery . SETTING This is a single-center study in a 15-bedded cardiothoracic intensive care unit ( ICU ) . PARTICIPANTS Participants are patients after coronary artery bypass grafting and /or aortic valve surgery . INTERVENTIONS Patients in the GDT group received cardiac output monitoring and fluid challenges targeting an increase in stroke volume by at least 10 % . Stroke volume maximization was maintained for a period of 8 hours from admission to the ICU . All other aspects of care were dictated by the clinical team . Patients in the st and ard therapy ( ST ) group had intravenous fluids in accordance with the routine practice of the unit . Patients were divided into the GDT and ST group dependant on availability of cardiac output monitors and allocation of nursing staff with training in GDT . Patients ' data were collected prospect ively in both groups . MEASUREMENTS AND MAIN RESULTS One hundred twenty-three patients received GDT compared with 141 patients in the ST group . Both groups received similar volumes of fluid ( GDT , 2905 [ 1367 ] mL vs 2704 [ 1393 ] mL ; P=.09 ) . Incidence of AKI was reduced in the GDT group ( n=8 [ 6.5 % ] vs n=28 [ 19.9 % ] ; P=.002 ) . The median duration of hospital stay was 6 ( 4 ) days in the GDT group vs 7 ( 8) days in the ST , P=.004 . CONCLUSION Postoperative GDT in patients after cardiac surgery was associated with reduction in the incidence of AKI and a reduction in ICU and hospital duration of stay Abstract . Objective : To compare the survival and clinical outcomes of critically ill patients treated with the use of a pulmonary artery catheter ( PAC ) to those treated without the use of a PAC . Design : Prospect i ve , r and omised , controlled , clinical trial from October 1997 to February 1999 . Setting : Adult intensive care unit at a large teaching hospital . Patients : Two hundred one critically ill patients were r and omised either to a PAC group ( n=95 ) or the control group ( n=106 ) . One patient in the control group was withdrawn from the study and five patients in the PAC group did not receive a PAC . All participants were available for follow-up . Interventions : Participants were assigned to be managed either with the use of a PAC ( PAC group ) or without the use of a PAC ( control group ) . Main outcome measures : Survival to 28 days , intensive care and hospital length of stay and organ dysfunction were compared on an intention-to-treat basis and also on a subgroup basis for those participants who successfully received a PAC . Results : There was no significant difference in mortality between the PAC group [ 46/95 ( 47.9 % ) ] and the control group [ 50/106 ( 47.6 ) ] ( 95 % confidence intervals for the difference –13 to 14 % , p>0.99 ) . The mortality for participants who had management decisions based on information derived from a PAC was 41/91 ( 45 % , 95 % confidence intervals –11 to 16 % , p=0.77 ) . The PAC group had significantly more fluids in the first 24 h ( 4953 ( 3140 , 7000 ) versus 4292 ( 2535 , 6049 ) ml ) and an increased incidence of renal failure ( 35 versus 20 % of patients at day 3 post r and omisation p<0.05 ) and thrombocytopenia ( p<0.03 ) . Conclusions : These results suggest that the PAC is not associated with an increased mortality BACKGROUND The benefits of stroke volume optimization during surgery are unclear , with recent data not replicating the positive effects of earlier studies . METHODS This was a r and omized controlled trial of st and ard fluid therapy with or without supplementary blinded intraoperative stroke volume optimization in 220 patients having major elective rectal resection or cystectomy with ileal conduit . All patients were treated using a contemporary enhanced recovery pathway . Interventional fluid challenges used Gelofusine ( B Braun , Germany ) , guided by stoke volume variability measured by LiDCOrapid ( LiDCO , UK ) . Participants were stratified by aerobic fitness ( characterized by preoperative cardiopulmonary exercise test ) , surgical specialty , and intended surgical approach ( open or laparoscopic ) . The primary outcome was the prevalence of moderate or severe complications on day 5 after surgery , defined using the postoperative morbidity survey ( POMS ) criteria . RESULTS Patients received ∼13 ml kg(-1 ) h(-1 ) of i.v . fluids during surgery . The intervention group received an additional mean ( sd ) 956 ( 896 ) ml Gelofusine . There were no statistically significant differences between groups in any primary or secondary end point . A positive POMS on postoperative day 5 was noted in 54 of 111 control subjects ( 48.6 % ) and 55 of 109 participants in the intervention group [ 50.5 % ; adjusted odds ratio 0.90 ( 95 % confidence interval 0.52 - 1.57 ) , P=0.717 ] . Mean ( sd ) hospital length of stay was 9.6 ( 6.8 ) days in the control group and 11.8 ( 11.5 ) days in the intervention group ( adjusted difference -2.1 ( -4.6 to 0.3 ) days , P=0.091 ) . There was no statistical interaction between stroke volume optimization and aerobic fitness in terms of rate of complications or length of stay . CONCLUSIONS Algorithm-driven stroke volume optimization is of no benefit when superimposed on a liberal baseline fluid regimen in patients having elective major abdominal surgery , when stratified to minimize differences in fitness and surgical approach between groups . CLINICAL TRIAL REGISTRATION IS RCT N21597243 BACKGROUND Postoperative organ failures commonly occur after major abdominal surgery , increasing the utilization of re sources and costs of care . Tissue hypoxia is a key trigger of organ dysfunction . A therapeutic strategy design ed to detect and reverse tissue hypoxia , as diagnosed by an increase of oxygen extraction ( O2ER ) over a predefined threshold , could decrease the incidence of organ failures . The primary aim of this study was to compare the number of patients with postoperative organ failure and length of hospital stay between those r and omized to conventional vs a protocol ized strategy design ed to maintain O2ER < 27 % . METHODS A prospect i ve , r and omized , controlled trial was performed in nine hospitals in Italy . One hundred thirty-five high-risk patients scheduled for major abdominal surgery were r and omized in two groups . All patients were managed to achieve st and ard goals : mean arterial pressure > 80 mm Hg and urinary output > 0.5 mL/kg/h . The patients of the " protocol group " ( group A ) were also managed to keep O2ER < 27 % . MEASUREMENTS AND MAIN RESULTS In group A , fewer patients had at least one organ failure ( n = 8 , 11.8 % ) than in group B ( n = 20 , 29.8 % ) [ p < 0.05 ] , and the total number of organ failures was lower in group A than in group B ( 27 failures vs 9 failures , p < 0.001 ) . Length of hospital stay was significantly lower in the protocol group than in the control group ( 11.3 + /- 3.8 days vs 13.4 + /- 6.1 days , p < 0.05 ) . Hospital mortality was similar in both groups . CONCLUSIONS Early treatment directed to maintain O2ER at < 27 % reduces organ failures and hospital stay of high-risk surgical patients . Clinical trials.gov reference No. NCT00254150 The objective was to test prospect ively supranormal values of cardiac index ( CI ) , oxygen delivery index ( DO2I ) , and oxygen consumption index ( VO2I ) as resuscitation goals to improve outcome in severely traumatized patients . We included patients > or = 16 years of age who had either ( 1 ) an estimated blood loss > or = 2000 mL or ( 2 ) a pelvic fracture and /or two or more major long bone fractures with > or = four units of packed red cells given within six hours of admission . The protocol resuscitation goals were CI > or = 4.5 L/min/m2 , DO2I > or = 670 mL/min/m2 , and VO2I > or = 166 mL/min/m2 within 24 hours of admission . The control resuscitation goals were normal vital signs , urine output , and central venous pressure . The 50 protocol patients had a significantly lower mortality ( 9 of 50 , 18 % vs. 24 of 65 , 37 % ) and fewer organ failures per patient ( 0.74 + /- 0.28 vs. 1.62 + /- 0.45 ) than did the 75 control patients . We conclude that increased CI , DO2I , and VO2I seen in survivors of severe trauma are primary compensations that have survival value ; augmentation of these compensations compared to conventional therapy decreases mortality Oliguria is a valuable marker of kidney function and a criterion for diagnosing and staging acute kidney injury ( AKI ) . However , the utility of urine output as a specific metric for renal dysfunction is somewhat controversial . To study this issue further we tested whether urine output is a sensitive , specific , and early measure for diagnosing and staging AKI in 317 critically ill patients in a prospect i ve observational study . Urine output was assessed every hour and serum creatinine every 12 to 24 h. The sensitivity and specificity of different definitions of oliguria for the diagnosis of AKI were compared with the Acute Kidney Injury Network serum creatinine criterion . The incidence of AKI increased from 24 % , based solely on serum creatinine , to 52 % by adding the urine output as a diagnostic criterion . Oliguric patients without a change in serum creatinine had an intensive care unit mortality rate ( 8.8 % ) significantly higher than patients without AKI ( 1.3 % ) , and similar to oliguric patients with an increase in serum creatinine ( 10.4 % ) . The diagnosis of AKI occurred earlier in oliguric than in non-oliguric patients . Oliguria of more than 12 h and oliguria of 3 or more episodes were associated with an increased mortality rate . Thus , urine output is a sensitive and early marker for AKI and is associated with adverse outcomes in intensive care unit patients BACKGROUND Intraoperative fluid therapy regimens using oesophageal Doppler monitoring ( ODM ) to optimize stroke volume ( SV ) ( goal -directed fluid therapy , GDT ) have been associated with a reduction in length of stay ( LOS ) and complication rates after major surgery . We hypothesized that intraoperative GDT would reduce the time to surgical readiness for discharge ( RfD ) of patients having major elective colorectal surgery but that this effect might be less marked in aerobically fit patients . METHODS In this double-blinded controlled trial , 179 patients undergoing major open or laparoscopic colorectal surgery were characterized as aerobically ' fit ' ( n=123 ) or ' unfit ' ( n=56 ) on the basis of their performance during a cardiopulmonary exercise test . Within these fitness strata , patients were r and omized to receive a st and ard fluid regimen with or without ODM-guided intraoperative GDT . RESULTS GDT patients received an average of 1360 ml of additional intraoperative colloid . The mean cardiac index and SV at skin closure were significantly higher in the GDT group than in controls . Times to RfD and LOS were longer in GDT than control patients but did not reach statistical significance ( median 6.8 vs 4.9 days , P=0.09 , and median 8.8 vs 6.7 days , P=0.09 , respectively ) . Fit GDT patients had an increased RfD ( median 7.0 vs 4.7 days ; P=0.01 ) and LOS ( median 8.8 vs 6.0 days ; P=0.01 ) compared with controls . CONCLUSIONS Intraoperative SV optimization conferred no additional benefit over st and ard fluid therapy . In an aerobically fit subgroup of patients , GDT was associated with detrimental effects on the primary outcome . TRIAL REGISTRY UK NIHR CRN 7285 , IS RCT N 14680495 . http://public.ukcrn.org.uk/ Search / Study Detail.aspx ? Study ID=7285 BACKGROUND The optimal perioperative fluid resuscitation strategy for liver resections remains undefined . Goal -directed therapy ( GDT ) embodies a number of physiologic strategies to achieve an ideal fluid balance and avoid the consequences of over- or under-resuscitation . STUDY DESIGN In a prospect i ve r and omized trial , patients undergoing liver resection were r and omized to GDT using stroke volume variation as an end point or to st and ard perioperative resuscitation . Primary outcomes measure was 30-day morbidity . RESULTS Between 2012 and 2014 , one hundred and thirty-five patients were r and omized ( GDT : n = 69 ; st and ard perioperative resuscitation : n = 66 ) . Median age was 57 years and 56 % were male . Metastatic disease comprised 81 % of patients . Overall ( 35 % GDT vs 36 % st and ard perioperative resuscitation ; p = 0.86 ) and grade 3 morbidity ( 28 % GDT vs 18 % st and ard perioperative resuscitation ; p = 0.22 ) were equivalent . Patients in the GDT arm received less intraoperative fluid ( mean 2.0 L GDT vs 2.9 L st and ard perioperative resuscitation ; p < 0.001 ) . Perioperative transfusions were required in 4 % ( 6 % GDT vs 2 % st and ard perioperative resuscitation ; p = 0.37 ) and boluses in the postanesthesia care unit were administered to 24 % ( 29 % GDT vs 20 % st and ard perioperative resuscitation ; p = 0.23 ) . Mortality rate was 1 % ( 2 of 135 patients ; both in GDT ) . On multivariable analysis , male sex , age , combined procedures , higher intraoperative fluid volume , and fluid boluses in the postanesthesia care unit were associated with higher 30-day morbidity . CONCLUSIONS Stroke volume variation-guided GDT is safe in patients undergoing liver resection and led to less intraoperative fluid . Although the incidence of postoperative complications was similar in both arms , lower intraoperative resuscitation volume was independently associated with decreased postoperative morbidity in the entire cohort . Future studies should target extensive resections and identify patients receiving large resuscitation volumes , as this population is more likely to benefit from this technique RATIONALE It is unknown whether lactate monitoring aim ed to decrease levels during initial treatment in critically ill patients improves outcome . OBJECTIVES To assess the effect of lactate monitoring and resuscitation directed at decreasing lactate levels in intensive care unit ( ICU ) patients admitted with a lactate level of greater than or equal to 3.0 mEq/L. METHODS Patients were r and omly allocated to two groups . In the lactate group , treatment was guided by lactate levels with the objective to decrease lactate by 20 % or more per 2 hours for the initial 8 hours of ICU stay . In the control group , the treatment team had no knowledge of lactate levels ( except for the admission value ) during this period . The primary outcome measure was hospital mortality . MEASUREMENTS AND MAIN RESULTS The lactate group received more fluids and vasodilators . However , there were no significant differences in lactate levels between the groups . In the intention-to-treat population ( 348 patients ) , hospital mortality in the control group was 43.5 % ( 77/177 ) compared with 33.9 % ( 58/171 ) in the lactate group ( P = 0.067 ) . When adjusted for predefined risk factors , hospital mortality was lower in the lactate group ( hazard ratio , 0.61 ; 95 % confidence interval , 0.43 - 0.87 ; P = 0.006 ) . In the lactate group , Sequential Organ Failure Assessment scores were lower between 9 and 72 hours , inotropes could be stopped earlier , and patients could be weaned from mechanical ventilation and discharged from the ICU earlier . CONCLUSIONS In patients with hyperlactatemia on ICU admission , lactate-guided therapy significantly reduced hospital mortality when adjusting for predefined risk factors . As this was consistent with important secondary endpoints , this study suggests that initial lactate monitoring has clinical benefit . Clinical trial registered with www . clinical trials.gov ( NCT00270673 ) Objectives : To evaluate the effects of goal -directed therapy on outcomes in high-risk patients undergoing cardiac surgery . Design : A prospect i ve r and omized controlled trial and an up date d meta analysis of r and omized trials published from inception up to May 1 , 2015 . Setting : Surgical ICU within a tertiary referral university-affiliated teaching hospital . Patients : One hundred twenty-six high-risk patients undergoing coronary artery bypass surgery or valve repair . Interventions : Patients were r and omized to a cardiac output – guided hemodynamic therapy algorithm ( goal -directed therapy group , n = 62 ) or to usual care ( n = 64 ) . In the goal -directed therapy arm , a cardiac index of greater than 3 L/min/m2 was targeted with IV fluids , inotropes , and RBC transfusion starting from cardiopulmonary bypass and ending 8 hours after arrival to the ICU . Measurements and Main Results : The primary outcome was a composite endpoint of 30-day mortality and major postoperative complications . Patients from the goal -directed therapy group received a greater median ( interquartile range ) volume of IV fluids than the usual care group ( 1,000 [ 625–1,500 ] vs 500 [ 500–1,000 ] mL ; p < 0.001 ] , with no differences in the administration of either inotropes or RBC transfusions . The primary outcome was reduced in the goal -directed therapy group ( 27.4 % vs 45.3 % ; p = 0.037 ) . The goal -directed therapy group had a lower occurrence rate of infection ( 12.9 % vs 29.7 % ; p = 0.002 ) and low cardiac output syndrome ( 6.5 % vs 26.6 % ; p = 0.002 ) . We also observed lower ICU cumulative dosage of dobutamine ( 12 vs 19 mg/kg ; p = 0.003 ) and a shorter ICU ( 3 [ 3–4 ] vs 5 [ 4–7 ] d ; p < 0.001 ) and hospital length of stay ( 9 [ 8–16 ] vs 12 [ 9–22 ] d ; p = 0.049 ) in the goal -directed therapy compared with the usual care group . There were no differences in 30-day mortality rates ( 4.8 % vs 9.4 % , respectively ; p = 0.492 ) . The meta analysis identified six trials and showed that , when compared with st and ard treatment , goal -directed therapy reduced the overall rate of complications ( goal -directed therapy , 47/410 [ 11 % ] vs usual care , 92/415 [ 22 % ] ; odds ratio , 0.40 [ 95 % CI , 0.26–0.63 ] ; p < 0.0001 ) and decreased the hospital length of stay ( mean difference , –5.44 d ; 95 % CI , –9.28 to –1.60 ; p = 0.006 ) with no difference in postoperative mortality : 9 of 410 ( 2.2 % ) versus 15 of 415 ( 3.6 % ) , odds ratio , 0.61 ( 95 % CI , 0.26–1.47 ) , and p = 0.27 . Conclusions : Goal -directed therapy using fluids , inotropes , and blood transfusion reduced 30-day major complications in high-risk patients undergoing cardiac surgery BACKGROUND : Dynamic variables predict fluid responsiveness and may improve fluid management during surgery . We investigated whether displaying the variability in the pulse oximeter plethysmogram ( pleth variability index ; PVI ) would guide intraoperative fluid management and improve circulation as assessed by lactate levels . METHODS : Eighty-two patients scheduled for major abdominal surgery were r and omized into 2 groups to compare intraoperative PVI-directed fluid management ( PVI group ) versus st and ard care ( control group ) . After the induction of general anesthesia , the PVI group received a 500-mL crystalloid bolus and a crystalloid infusion of 2 mL · kg−1 · h−1 . Colloids of 250 mL were administered if the PVI was > 13 % Vasoactive drug support was given to maintain the mean arterial blood pressure above 65 mm Hg . In the control group , an infusion of 500 mL of crystalloids was followed by fluid management on the basis of fluid challenges and their effects on mean arterial blood and central venous pressure . Perioperative lactate levels , hemodynamic data , and postoperative complications were recorded prospect ively . RESULTS : Intraoperative crystalloids and total volume infused were significantly lower in the goal -directed PVI group . Lactate levels were significantly lower in the PVI group during surgery and 48 hours after surgery ( P < 0.05 ) . CONCLUSIONS : PVI-based goal -directed fluid management reduced the volume of intraoperative fluid infused and reduced intraoperative and postoperative lactate levels Survivors of high-risk surgical operations were previously observed to have significantly higher mean CI , DO2 , and VO2 than nonsurvivors . The hypothesis was proposed that increased CI and DO2 are circulatory compensations for increased postoperative metabolism . We tested this hypothesis in two series . In series 1 , prospect ively allocated by services , mortality and morbidity of the control group were significantly greater than those of the protocol group . In series 2 , patients who fulfilled previously defined high-risk criteria were preoperatively r and omized to one of three monitoring/treatment groups : CVP-control group , PA-control group and PA- protocol group . Postoperative mortalities in the CVP-control and PA-control groups were not statistically significantly different , but PA- protocol group mortality was significantly reduced compared with its control group . The PA- protocol group had reduced complications , duration of hospitalization , duration in ICU , and mechanical ventilation , and reduced costs when the PA catheter was placed preoperatively and used to augment circulatory responses For r and om effects meta- analysis , seven different estimators of the heterogeneity variance are compared and assessed using a simulation study . The seven estimators are the variance component type estimator ( VC ) , the method of moments estimator ( MM ) , the maximum likelihood estimator ( ML ) , the restricted maximum likelihood estimator ( REML ) , the empirical Bayes estimator ( EB ) , the model error variance type estimator ( MV ) , and a variation of the MV estimator ( MVvc ) . The performance of the estimators is compared in terms of both bias and mean squared error , using Monte Carlo simulation . The results show that the REML and especially the ML and MM estimators are not accurate , having large biases unless the true heterogeneity variance is small . The VC estimator tends to overestimate the heterogeneity variance in general , but is quite accurate when the number of studies is large . The MV estimator is not a good estimator when the heterogeneity variance is small to moderate , but it is reasonably accurate when the heterogeneity variance is large . The MVvc estimator is an improved estimator compared to the MV estimator , especially for small to moderate values of the heterogeneity variance . The two estimators MVvc and EB are found to be the most accurate in general , particularly when the heterogeneity variance is moderate to large OBJECTIVE To assess the effect of deliberate perioperative increase in oxygen delivery on mortality and morbidity in patients who are at high risk of both following surgery . DESIGN Prospect i ve , r and omized clinical trial . SETTING A teaching hospital general intensive care unit , London , Engl and . PATIENTS A total of 107 surgical patients , who were assessed as high risk from previously identified criteria , were studied during an 18-month period . INTERVENTIONS Patients were r and omly assigned to a control group ( n = 54 ) that received best st and ard perioperative care , or to a protocol group ( n = 53 ) that , in addition , had deliberate increase of oxygen delivery index to greater than 600 mL/min per square meter by use of dopexamine hydrochloride infusion . OUTCOME MEASURES Mortality and complications were assessed to 28 days postoperatively . RESULTS Groups were similar with respect to demographics , admission criteria , operation type , and admission hemodynamic variables . Groups were treated similarly to maintain blood pressure , arterial saturation , hemoglobin concentration , and pulmonary artery occlusion pressure ; however , once additional treatment with dopexamine hydrochloride had been given , the protocol group had significantly higher oxygen delivery preoperatively ( median , 597 vs 399 mL/min per square meter ; P < .001 ) and postoperatively ( P < .001 ) . Results indicate a 75 % reduction in mortality ( 5.7 % vs 22.2 % ; P = .015 ) and a halving of the mean ( + /- SEM ) number of complications per patient ( 0.68 [ + /- 0.16 ] vs 1.35 [ + /- 0.20 ] ; P = .008 ) in patients r and omized to the protocol group . CONCLUSION Perioperative increase of oxygen delivery with dopexamine hydrochloride significantly reduces mortality and morbidity in high-risk surgical patients Intra‐operative oesophageal Doppler monitor‐guided fluid management has been associated with improved postoperative length of hospital stay and morbidity in gastrointestinal and orthopaedic surgery . We design ed a r and omised controlled trial to test the hypothesis that this approach to intra‐operative fluid management in major elective open gynaecological surgery would shorten the length of postoperative stay , defined as time to readiness for hospital discharge . Postoperative morbidity was evaluated as a secondary outcome . The oesophageal Doppler monitor group underwent intra‐operative fluid management using an oesophageal Doppler‐guided stroke volume optimisation algorithm . Control group ( conventional fluid therapy ) intra‐operative fluid management was based on conventional haemodynamic indices . In a single centre , 102 patients were r and omly assigned : 51 to the oesophageal Doppler monitor group ( 51 analysed ) and 51 to the control group ( 50 analysed ) . Evaluators who were blinded to patient assignment collected postoperative outcome data . There was no difference in the length of postoperative hospital stay between the groups : median ( IQR [ range ] ) number of days until ready for discharge was 6 ( 5–8 [ 4–25 ] ) days in the oesophageal Doppler monitor group compared with 7 ( 5–9 [ 4–42 ] ) days in the control group , p = 0.5 . There was no difference between the groups in postoperative morbidity survey scores on postoperative days 1 , 3 or 5 . Seven patients in the oesophageal Doppler monitor group and 11 in the control group experienced postoperative complications ( p = 0.41 ) . These findings question whether intra‐operative oesophageal Doppler‐guided fluid therapy is of benefit in patients undergoing open gynaecological surgery Abstract Objectives : To assess whether intraoperative intravascular volume optimisation improves outcome and shortens hospital stay after repair of proximal femoral fracture . Design : Prospect i ve , r and omised controlled trial comparing conventional intraoperative fluid management with repeated colloid fluid challenges monitored by oesophageal Doppler ultrasonography to maintain maximal stroke volume throughout the operative period . Setting : Teaching hospital , London . Subjects : 40 patients undergoing repair of proximal femoral fracture under general anaesthesia . Interventions : Patients were r and omly assigned to receive either conventional intraoperative fluid management ( control patients ) or additional repeated colloid fluid challenges with oesophageal Doppler ultrasonography used to maintain maximal stroke volume throughout the operative period ( protocol patients ) . Main outcome measures : Time declared medically fit for hospital discharge , duration of hospital stay ( in acute bed ; in acute plus long stay bed ) , mortality , perioperative haemodynamic changes . Results : Intraoperative intravascular fluid loading produced significantly greater changes in stroke volume ( median 15 ml ( 95 % confidence interval 10 to 21 ml ) ) and cardiac output ( 1.2 l/min ( 0.1 to 2.3 l/min ) ) than in the conventionally managed group ( −5 ml ( −10 to 1 ml ) and −0.4 l/min ( −1.0 to 0.2 l/min ) ) ( P<0.001 and P<0.05 , respectively ) . One protocol patient and two control patients died in hospital . In the survivors , postoperative recovery was significantly faster in the protocol patients , with shorter times to being declared medically fit for discharge ( median 10 ( 9 to 15 ) days v 15 ( 11 to 40 ) days , P<0.05 ) and a 39 % reduction in hospital stay ( 12 ( 8 to 13 ) days v 20 ( 10 to 61 ) days , P<0.05 ) . Conclusions : Proximal femoral fracture repair constitutes surgery in a high risk population . Intraoperative intravascular volume loading to optimal stroke volume result ed in a more rapid postoperative recovery and a significantly reduced hospital stay . Key messages Patients undergoing hip fracture repair constitute a high risk group with considerable mortality and morbidity and an often protracted postoperative hospital stay These patients often have depleted intravascular volume in the perioperative period and rarely receive either invasive haemodynamic monitoring or high dependency care Haemodynamic optimisation guided by pulmonary artery catheter in the perioperative period has been shown to improve outcome in high risk patients undergoing major surgery , but this is not considered routinely practicable for hip fracture repair Intravascular volume optimisation directed by minimally invasive oesophageal Doppler monitoring in the intraoperative period significantly reduces hospital |
717 | 28,992,285 | Conversely , except for MIBs , RIPC had fewer non-significant effects under propofol with or without volatile anaesthetics .
Conclusions RIPC did not consistently reduce morbidity and mortality in adults undergoing cardiac surgery with CPB .
In the subgroup on volatile anaesthetics only , RIPC markedly and significantly reduced the incidence of AKI and composite endpoint as well as myocardial injury | Background The main aim of this systematic review was to assess whether remote ischaemic preconditioning ( RIPC ) protects kidneys and the heart in cardiac surgery with cardiopulmonary bypass ( CPB ) and to investigate a possible role of anaesthetic agents . | BACKGROUND Whether remote ischemic preconditioning ( transient ischemia and reperfusion of the arm ) can improve clinical outcomes in patients undergoing coronary-artery bypass graft ( CABG ) surgery is not known . We investigated this question in a r and omized trial . METHODS We conducted a multicenter , sham-controlled trial involving adults at increased surgical risk who were undergoing on-pump CABG ( with or without valve surgery ) with blood cardioplegia . After anesthesia induction and before surgical incision , patients were r and omly assigned to remote ischemic preconditioning ( four 5-minute inflations and deflations of a st and ard blood-pressure cuff on the upper arm ) or sham conditioning ( control group ) . Anesthetic management and perioperative care were not st and ardized . The combined primary end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , coronary revascularization , or stroke , assessed 12 months after r and omization . RESULTS We enrolled a total of 1612 patients ( 811 in the control group and 801 in the ischemic-preconditioning group ) at 30 cardiac surgery centers in the United Kingdom . There was no significant difference in the cumulative incidence of the primary end point at 12 months between the patients in the remote ischemic preconditioning group and those in the control group ( 212 patients [ 26.5 % ] and 225 patients [ 27.7 % ] , respectively ; hazard ratio with ischemic preconditioning , 0.95 ; 95 % confidence interval , 0.79 to 1.15 ; P=0.58 ) . Furthermore , there were no significant between-group differences in either adverse events or the secondary end points of perioperative myocardial injury ( assessed on the basis of the area under the curve for the high-sensitivity assay of serum troponin T at 72 hours ) , inotrope score ( calculated from the maximum dose of the individual inotropic agents administered in the first 3 days after surgery ) , acute kidney injury , duration of stay in the intensive care unit and hospital , distance on the 6-minute walk test , and quality of life . CONCLUSIONS Remote ischemic preconditioning did not improve clinical outcomes in patients undergoing elective on-pump CABG with or without valve surgery . ( Funded by the Efficacy and Mechanism Evaluation Program [ a Medical Research Council and National Institute of Health Research partnership ] and the British Heart Foundation ; ERICCA Clinical Trials.gov number , NCT01247545 . ) Background : Two preconditioning stimuli should induce a more consistent overall cell protection . We hypothesized that remote ischemic preconditioning ( RIPC , second preconditioning stimulus ) applied during isoflurane inhalation ( first preconditioning stimulus ) would provide more protection to the myocardium of patients undergoing on-pump coronary artery bypass grafting . Methods : In this placebo-controlled r and omized controlled study , patients in the RIPC group received four 5-min cycles of 300 mmHg cuff inflation/deflation of the leg before aortic cross-clamping . Anesthesia consisted of opioids and propofol for induction and isoflurane for maintenance . The primary outcome was high-sensitivity cardiac troponin T release . Secondary endpoints were plasma levels of N-terminal pro-brain natriuretic peptide , high-sensitivity C-reactive protein , S100 protein , and short- and long-term clinical outcomes . Gene expression profiles were obtained from atrial tissue using microarrays . Results : RIPC ( n = 27 ) did not reduce high-sensitivity cardiac troponin T release when compared with placebo ( n = 28 ) . Likewise , N-terminal pro-brain natriuretic peptide , a marker of myocardial dysfunction ; high-sensitivity C-reactive protein , a marker of perioperative inflammatory response ; and S100 , a marker of cerebral injury , were not different between the groups . The incidence for the perioperative composite endpoint combining new arrhythmias and myocardial infa rct ions was higher in the RIPC group than the placebo group ( 14/27 vs. 6/28 , P = 0.036 ) . However , there was no difference in the 6-month cardiovascular outcome . N-terminal pro-brain natriuretic peptide release correlated with isoflurane-induced transcriptional changes in fatty-acid metabolism ( P = 0.001 ) and DNA-damage signaling ( P < 0.001 ) , but not with RIPC-induced changes in gene expression . Conclusions : RIPC applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass grafting BACKGROUND Remote ischemic preconditioning ( RIPC ) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery , but uncertainty about clinical outcomes remains . METHODS We conducted a prospect i ve , double-blind , multicenter , r and omized , controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol . The trial compared upper-limb RIPC with a sham intervention . The primary end point was a composite of death , myocardial infa rct ion , stroke , or acute renal failure up to the time of hospital discharge . Secondary end points included the occurrence of any individual component of the primary end point by day 90 . RESULTS A total of 1403 patients underwent r and omization . The full analysis set comprised 1385 patients ( 692 in the RIPC group and 693 in the sham-RIPC group ) . There was no significant between-group difference in the rate of the composite primary end point ( 99 patients [ 14.3 % ] in the RIPC group and 101 [ 14.6 % ] in the sham-RIPC group , P=0.89 ) or of any of the individual components : death ( 9 patients [ 1.3 % ] and 4 [ 0.6 % ] , respectively ; P=0.21 ) , myocardial infa rct ion ( 47 [ 6.8 % ] and 63 [ 9.1 % ] , P=0.12 ) , stroke ( 14 [ 2.0 % ] and 15 [ 2.2 % ] , P=0.79 ) , and acute renal failure ( 42 [ 6.1 % ] and 35 [ 5.1 % ] , P=0.45 ) . The results were similar in the per- protocol analysis . No treatment effect was found in any subgroup analysis . No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release , the duration of mechanical ventilation , the length of stay in the intensive care unit or the hospital , new onset of atrial fibrillation , and the incidence of postoperative delirium . No RIPC-related adverse events were observed . CONCLUSIONS Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery . ( Funded by the German Research Foundation ; RIPHeart Clinical Trials.gov number , NCT01067703 . ) BACKGROUND Although remote ischemic preconditioning ( RIPC ) has emerged as an attractive strategy to reduce cardiac injury in patients undergoing diverse cardiac surgical procedures , it is unclear whether RIPC has protective effects in patients undergoing aortic valve replacement surgery without coronary artery bypass grafting ( CABG ) . METHODS Hence , 100 adult patients undergoing elective aortic valve replacement for aortic valve stenosis , without combined surgery with CABG , were prospect ively r and omly assigned in a 1:1 ratio to either the RIPC group or the control group . The RIPC group underwent three cycles of 5-min inflation to 200mmHg and 5-min deflation of an automated upper-arm cuff inflator after induction of anesthesia . The control group had a deflated cuff placed on upper arm for 30min . The primary endpoint was 72-h area under curve ( AUC ) for troponin I ( cTnI ) . Secondary endpoints were 72-h AUC for creatine kinase-MB isoenzyme ( CK-MB ) release , incidence of acute kidney injury , extubation time , length of stay in intensive care unit , and simplified acute physiology score ( SAPS II ) . RESULTS There were no significant differences in cTnI AUC [ 195±190 arbitrary units ( a.u . ) in RIPC group vs. 169±117 a.u . in the control group ; p=0.41 ] and CK-MB AUC between groups . None of the other secondary endpoints differed between groups . Acute kidney injury occurred in 12 patients ( 24.5 % ) in the control group and in 13 ( 26.0 % ) in the RIPC group ( p=0.86 ) . CONCLUSIONS RIPC did not exhibit significant cardiac or kidney protective effects in patients undergoing aortic valve replacement surgery without CABG Background Remote ischemic preconditioning ( RIPC ) has been shown to enhance the tolerance of remote organs to cope with a subsequent ischemic event . We hypothesized that RIPC reduces postoperative neurocognitive dysfunction ( POCD ) in patients undergoing complex cardiac surgery . Methods We conducted a prospect i ve , r and omized , double-blind , controlled trial including 180 adult patients undergoing elective cardiac surgery with cardiopulmonary bypass . Patients were r and omized either to RIPC or to control group . Primary endpoint was postoperative neurocognitive dysfunction 5–7 days after surgery assessed by a comprehensive test battery . Cognitive change was assumed if the preoperative to postoperative difference in 2 or more tasks assessing different cognitive domains exceeded more than one SD ( 1 SD criterion ) or if the combined Z score was 1.96 or greater ( Z score criterion ) . Results According to 1 SD criterion , 52 % of control and 46 % of RIPC patients had cognitive deterioration 5–7 days after surgery ( p = 0.753 ) . The summarized Z score showed a trend to more cognitive decline in the control group ( 2.16±5.30 ) compared to the RIPC group ( 1.14±4.02 ; p = 0.228 ) . Three months after surgery , incidence and severity of neurocognitive dysfunction did not differ between control and RIPC . RIPC tended to decrease postoperative troponin T release at both 12 hours [ 0.60 ( 0.19–1.94 ) µg/L vs. 0.48 ( 0.07–1.84 ) µg/L ] and 24 hours after surgery [ 0.36 ( 0.14–1.89 ) µg/L vs. 0.26 ( 0.07–0.90 ) µg/L ] . Conclusions We failed to demonstrate efficacy of a RIPC protocol with respect to incidence and severity of POCD and secondary outcome variables in patients undergoing a wide range of cardiac surgery . Therefore , definitive large-scale multicenter trials are needed . Trial Registration Clinical Trials.gov Acute kidney injury ( AKI ) is a frequent complication of cardiac surgery and usually occurs in patients with preexisting chronic kidney disease ( CKD ) . Remote ischemic preconditioning ( RIPC ) may mitigate the renal ischemia-reperfusion injury associated with cardiac surgery and may be a preventive strategy for postsurgical AKI . We undertook a r and omized controlled trial of RIPC to prevent AKI in 86 patients with CKD ( estimated glomerular filtration rate under 60 ml/min per 1.73 m(2 ) ) undergoing coronary artery bypass graft ( CABG ) surgery . Forty-three patients each were r and omized to receive st and ard care with or without RIPC consisting of three 5-minute cycles of forearm ischemia followed by reperfusion . The primary end point was the development of AKI defined as an increase in serum creatinine concentration over 0.3 mg/dl within 48 h of surgery . Secondary end points included a comparison between the study and control groups of several serum biomarkers of renal injury including cystatin-C , neutrophil gelatinase-associated lipocalin ( NGAL ) , and interleukin-18 ( IL-18 ) , and urinary biomarkers including NGAL , IL-18 , and kidney injury molecule-1 measured at 6 , 12 , and 24 h after CABG , and the 72-h serum troponin T concentration area under the curve as a marker of myocardial injury . Clinical and operative characteristics were similar between the preconditioned and control groups . AKI developed in 12 patients in both groups within 48 h of CABG . There were no significant differences between the two groups in the concentrations of any of the serum or urinary biomarkers of renal or cardiac injury after CABG . Thus , RIPC induced by forearm ischemia-reperfusion had no effect on the frequency of AKI after CABG in patients with CKD Background : Remote ischemic preconditioning is a simple therapy that may reduce cardiac and kidney injury . We undertook a r and omized controlled trial to evaluate the effect of this therapy on markers of heart and kidney injury after cardiac surgery . Methods : Patients at high risk of death within 30 days after cardiac surgery were r and omly assigned to undergo remote ischemic preconditioning or a sham procedure after induction of anesthesia . The preconditioning therapy was three 5-minute cycles of thigh ischemia , with 5 minutes of reperfusion between cycles . The sham procedure was identical except that ischemia was not induced . The primary outcome was peak creatine kinase – myocardial b and ( CK-MB ) within 24 hours after surgery ( expressed as multiples of the upper limit of normal , with log transformation ) . The secondary outcome was change in creatinine level within 4 days after surgery ( expressed as log-transformed micromoles per litre ) . Patient-important outcomes were assessed up to 6 months after r and omization . Results : We r and omly assigned 128 patients to remote ischemic preconditioning and 130 to the sham therapy . There were no significant differences in postoperative CK-MB ( absolute mean difference 0.15 , 95 % confidence interval [ CI ] −0.07 to 0.36 ) or creatinine ( absolute mean difference 0.06 , 95 % CI −0.10 to 0.23 ) . Other outcomes did not differ significantly for remote ischemic preconditioning relative to the sham therapy : for myocardial infa rct ion , relative risk ( RR ) 1.35 ( 95 % CI 0.85 to 2.17 ) ; for acute kidney injury , RR 1.10 ( 95 % CI 0.68 to 1.78 ) ; for stroke , RR 1.02 ( 95 % CI 0.34 to 3.07 ) ; and for death , RR 1.47 ( 95 % CI 0.65 to 3.31 ) . Interpretation : Remote ischemic precnditioning did not reduce myocardial or kidney injury during cardiac surgery . This type of therapy is unlikely to substantially improve patient-important outcomes in cardiac surgery . Trial registration : Clinical Trials.gov , no. NCT01071265 Background Novel treatment strategies are required to reduce the development of acute kidney injury ( AKI ) in patients undergoing cardiac surgery . In this respect , remote ischemic preconditioning ( RIPC ) , a phenomenon in which transient nonlethal ischemia applied to an organ or tissue protects another organ or tissue from subsequent lethal ischemic injury , is a potential renoprotective strategy . Study Design Secondary analysis of 2 r and omized trials . Setting & Participants 78 consenting selected nondiabetic patients in a university teaching hospital undergoing elective coronary artery bypass graft ( CABG ) surgery recruited to 2 previously reported r and omized studies . Intervention RIPC consisted of three 5-minute cycles of right forearm ischemia , induced by inflating a blood pressure cuff on the upper arm to 200 mm Hg , with an intervening 5 minutes of reperfusion , during which time the cuff was deflated . The control consisted of placing an uninflated cuff on the arm for 30 minutes . Outcomes AKI measured using Acute Kidney Injury Network ( AKIN ) criteria , duration of hospital stay , in-hospital and 30-day mortality . Results Numbers of participants with AKI stages 1 , 2 , and 3 were 1 ( 3 % ) , 3 ( 8 % ) , and 0 in the intervention group compared with 10 ( 25 % ) , 0 , and 0 in the control group , respectively ( P = 0.005 ) . The decrease in AKI was independent of the effect of concomitant aortic valve replacement and cross-clamp times , which were distributed unevenly between the 2 groups . Limitations Retrospective analysis of data . More patients in the RIPC group underwent concomitant aortic valve replacement with CABG ; although we have corrected statistically for this imbalance , it remains an important confounding variable . Conclusions RIPC induced using transient forearm ischemia decreased the incidence of AKI in nondiabetic patients undergoing elective CABG surgery in this retrospective analysis . A large prospect i ve clinical trial is required to study this effect and clinical outcomes in patients undergoing cardiac surgery Background — We assessed whether remote ischemic preconditioning ( RIPC ) improves myocardial , renal , and lung protection after on-pump coronary surgery . Methods and Results — This was a single-center , prospect i ve , r and omized ( 1:1 ) , placebo-controlled trial . Patients , investigators , anesthetists , surgeons , and critical care teams were blinded to group allocation . Subjects received RIPC ( or placebo ) stimuli ( ×3 upper limb ( or dummy arm ) , 5-minute cycles of 200 mm Hg cuff inflation/deflation ) before aortic clamping . Anesthesia , perfusion , cardioplegia , and surgical techniques were st and ardized . The primary end point was 48-hour area under the curve ( AUC ) troponin T ( cTnT ) release . Secondary end points were 6-hour and peak cTnT , ECG changes , cardiac index , inotrope and vasoconstrictor use , renal dysfunction , and lung injury . Hospital survival was 99.4 % . Comparing placebo and RIPC , median ( interquartile range ) AUC 48-hour cTnT ( ng/mL−1/48 h−1 ) ; 28 ( 19 , 39 ) versus 30 ( 22 , 38 ) , 6-hour cTnT ( ng/mL−1 ) ; 0.93(0.59 , 1.35 ) versus 1.01(0.72 , 1.43 ) , peak cTnT ( ng/mL−1 ) ; 1.02 ( 0.74 , 1.44 ) versus 1.04 ( 0.78 , 1.51 ) , de novo left bundle-branch block ( 4 % versus 0 % ) and Q waves ( 5.3 % versus 5.5 % ) , serial cardiac indices , intraaortic balloon pump usage ( 8.5 % versus 7.5 % ) , inotrope ( 39 % versus 50 % ) and vasoconstrictor usage ( 66 % versus 64 % ) were not different . Dialysis requirement ( 1.2 % versus 3.8 % ) , peak creatinine ( median [ interquartile range ] , 1.2 mg/dL−1 ( 1.1 , 1.4 ) versus 1.2 ( 1.0 , 1.4 ) ) , and AUC urinary albumin-creatinine ratios 69 ( 40 , 112 ) versus 58 ( 32 , 85 ) were not different . Intubation times ; median ( interquartile range ) , 937 minutes(766 , 1402 ) versus 895(675 , 1180 ) , 6-hour ; 278 ( 210 , 338 ) versus 270 ( 218 , 323 ) and 12-hour pO2:FiO2 ratios 255 ( 195 , 323 ) versus 263 ( 210 , 308 ) were similar . Conclusions — In contrast to prior smaller studies , RIPC did not reduce troponin release , improve hemodynamics , or enhance renal or lung protection . Clinical Trial Registration — URL : http://www.ukcrn.org.uk . Unique identifier : 4659 Objectives Remote ischaemic preconditioning ( RIPC ) , using brief cycles of limb ischaemia/reperfusion , is a non-invasive , low-cost intervention that may reduce perioperative myocardial injury ( PMI ) in patients undergoing cardiac surgery . We investigated whether RIPC can also improve short-term clinical outcomes . Methods One hundred and eighty patients undergoing elective coronary artery bypass graft ( CABG ) surgery and /or valve surgery were r and omised to receive either RIPC ( 2–5 min cycles of simultaneous upper arm and thigh cuff inflation/deflation ; N=90 ) or control ( uninflated cuffs placed on the upper arm and thigh ; N=90 ) . The study primary end point was PMI , measured by 72 h area under the curve ( AUC ) serum high-sensitive troponin-T ( hsTnT ) ; secondary end point included short-term clinical outcomes . Results RIPC reduced PMI magnitude by 26 % ( −9.303 difference ( CI −15.618 to −2.987 ) 72 h hsTnT-AUC ; p=0.003 ) compared with control . There was also evidence that RIPC reduced the incidence of postoperative atrial fibrillation by 54 % ( 11 % RIPC vs 24 % control ; p=0.031 ) and decreased the incidence of acute kidney injury by 48 % ( 10.0 % RIPC vs 21.0 % control ; p=0.063 ) , and intensive care unit stay by 1 day ( 2.0 days RIPC ( CI 1.0 to 4.0 ) vs 3.0 days control ( CI 2.0 to 4.5 ) ; p=0.043 ) . In a post hoc analysis , we found that control patients administered intravenous glyceryl trinitrate ( GTN ) intraoperatively sustained 39 % less PMI compared with those not receiving GTN , and RIPC did not appear to reduce PMI in patients given GTN . Conclusions RIPC reduced the extent of PMI in patients undergoing CABG and /or valve surgery . RIPC may also have beneficial effects on short-term clinical outcomes , although this will need to be confirmed in future studies . Trial registration number Clinical Trials.gov ID : NCT00397163 Background : Remote ischaemic preconditioning ( RIPC ) induced by brief ischaemia and reperfusion of the arm reduces myocardial injury in coronary artery bypass ( CABG ) surgery patients receiving predominantly cross-clamp fibrillation for myocardial protection . However , cold-blood cardioplegia is the more commonly used method world wide . Objective : To assess whether RIPC is cardioprotective in CABG patients receiving cold-blood cardioplegia . Design : Single-centre , single-blinded , r and omised controlled trial . Setting : Tertiary referral hospital in London . Patients : Adults patients ( 18–80 years ) undergoing elective CABG surgery with or without concomitant aortic valve surgery with cold-blood cardioplegia . Patients with diabetes , renal failure ( serum creatinine > 130 mmol/l ) , hepatic or pulmonary disease , unstable angina or myocardial infa rct ion within the past 4 weeks were excluded . Interventions : Patients were r and omised to receive either RIPC ( n = 23 ) or control ( n = 22 ) after anaesthesia . RIPC comprised three 5 min cycles of right forearm ischaemia , induced by inflating a blood pressure cuff on the upper arm to 200 mm Hg , with an intervening 5 min reperfusion . The control group had a deflated cuff placed on the upper arm for 30 min . Main outcome measures : Serum troponin T was measured preoperatively and at 6 , 12 , 24 , 48 and 72 h after surgery and the area under the curve ( AUC at 72 h ) calculated . Results : RIPC reduced absolute serum troponin T release by 42.4 % ( mean ( SD ) AUC at 72 h : 31.53 ( 24.04 ) μg/l.72 h in controls vs 18.16 ( 6.67 ) μg/l.72 h in RIPC ; 95 % CI 2.4 to 24.3 ; p = 0.019 ) . Conclusions : Remote ischaemic preconditioning induced by brief ischaemia and reperfusion of the arm reduces myocardial injury in CABG surgery patients undergoing cold-blood cardioplegia , making this non-invasive cardioprotective technique widely applicable clinical ly . Trial registration number : NCT00397163 BACKGROUND To evaluate the impact of remote ischemic preconditioning ( RIPC ) on clinical outcome , biological markers of myocardial injury , and its safety in patients undergoing on-pump coronary artery bypass grafting ( CABG ) . MATERIAL AND METHODS This study was conducted at Ch . Pervaiz Elahi Institute of Cardiology ( CPEIC ) in Multan . The study took place from March 2012 to June 2013 . Patients were r and omly placed into two groups . Group A ( N = 32 ) did not undergo RIPC ; Group B ( N = 35 ) received RIPC after induction of anesthesia . Similar st and ard general anesthesia , cardiopulmonary technique , myocardial protection strategies , and surgical techniques were used in both groups except the protocol for RIPC . Following postoperative outcome , i.e. cardiac defibrillation after removal of aortic cross clamp during the period of rewarming , dem and for intra-aortic balloon pump ( IABP ) , dem and for antiarrhythmic before leaving the operation room , postoperative creatine kinase-myocardial b and ( CK-MB ) level ( at 1h , 12h , 24h , and 48h after surgery ) , postoperative serum creatinine level on first postoperative day , postoperative ejection fraction ( EF ) on third postoperative day , in-hospital mortality , and one-year mortality were noted , prospect ively . Safety of protocol of RIPC was estimated by limb ischemia monitored by pulse oximetry during and after procedure of RIPC and postoperative neurapraxia by nerve examination of right upper limb . RESULTS Post aortic cross clamp release cardiac defibrillation , dem and for IABP , dem and for high inotropes , and use of antiarrhythmic in the operation room were statistically insignificant in the non-RIPC and RIPC group with P values of .54 , .78 , .16 , and .16 , respectively . Mean postoperative CK-MB level ( IU/L ) showed the following results : At 1h ( Group A 20.94 + 1.66 , Group B 20.57 + 1.54 , P = .35 ) , at 12h ( Group A 27.13 + 1.85 , Group B 28.05 + 3.04 , P = .135 ) , at 24h ( Group A 27.63 + 1.7 , Group B 27.85 + 2.2 , P = .63 ) , and at 48h ( Group A 22.95 + 2.76 , Group B 23.27 + 3.6 , P = .69 ) . First postoperative day serum creatinine ( Group A 1.29 + 0.395 , Group B 1.33 + 0.57 , P = .77 ) and postoperative ejection fraction percentage on the third postoperative day ( Group A 50.78 + 8.72 , Group B 50.57 + 8.38 , P = .92 ) showed no statistical difference between two groups . Postoperative low cardiac output state , in-hospital mortality , and one-year mortality also were statistically insignificant between the groups with P values of .93 , .29 , and .33 , respectively . None of the patients in either group showed evidence of limb ischemia and neurapraxia of the right upper limb . CONCLUSION RIPC is a safe technique , but it does not have additional clinical benefit after on-pump CABG surgery in the presence of a st and ard myocardial protective strategy Abstract Objectives . The objective was to investigate the potential protective effects of two conditioning methods , on myocardial ischemic and reperfusion injury in relation to cardiac surgery . Design . Totally 68 patients were r and omly assigned to either a control group ( n = 23 ) , a remote ischemic preconditioning ( RIPC ) group ( n = 23 ) or a glucagon-like peptide-1 ( GLP-1 ) analogue group ( n = 22 ) . The RIPC protocol consisted of three cycles of upper limb ischemia . The GLP-1 analogue protocol consisted of intravenous infusion with exenatide . The primary endpoint was postoperative cardiac enzyme release . The other secondary endpoints were metabolic parameters related to myocardial ischemia , measured using microdialysis technique , as well as other operative- and postoperative data . Results . Postoperative cardiac enzyme release indicated a possible beneficial effect of the interventions , but the difference did not reach statistical significance . RIPC showed a trend toward lower levels ( p = 0.07 ) . We managed to establish a functional myocardial microdialysis model , but we were unable to demonstrate clear protective effects . Conclusions . We were in this prospect i ve r and omized proof-of-concept trial , unable to show distinct protective effects of the studied conditioning methods . However , this trial can hopefully contribute to generate a productive discussion concerning limitations and future use of cardiac conditioning as well as microdialysis technique Rationale : The heart can be protected from infa rct ion by brief episodes of ischemia/reperfusion of a remote organ . Remote ischemic preconditioning ( RIPC ) by brief arm ischemia/reperfusion has been recruited in patients undergoing coronary artery bypass surgery or percutaneous coronary interventions and during transport to the hospital for acute myocardial infa rct ion . Cardioprotective signaling has been extensively characterized in animal experiments . Objective : To identify cardioprotective signaling by RIPC in humans . Methods and Results : RIPC was induced by 3 cycles of 5 minutes of arm ischemia/5 minutes of reperfusion in patients undergoing coronary artery bypass surgery . Twelve patients each were r and omly assigned to undergo RIPC or a sham control procedure . Protection was confirmed by reduced serum troponin I concentrations in patients with RIPC versus control patients . In myocardial biopsies , an array of established cardioprotective proteins was analyzed by Western immunoblotting . The phosphorylation of signal transducer and activator of transcription 5 ( STAT5 ) increased from baseline before ischemic cardioplegic arrest to 10 minutes of reperfusion with RIPC , and STAT5 phosphorylation during reperfusion was greater in patients with RIPC than in control patients . Conclusions : The identification of this unique signaling signature of RIPC will facilitate the development of pharmacological cardioprotection . Clinical Trial Registration : URL : http://www . clinical trials.gov . Unique identifier : NCT01406678 Acute kidney injury , a common complication of cardiac surgery with cardiopulmonary bypass , is associated with increased morbidity and mortality . Ischemic preconditioning at a remote site mitigates ischemia-reperfusion injury and may prevent acute kidney injury after cardiac surgery , thus providing clinical benefit . To further study this , we enrolled 120 adult patients undergoing elective cardiac surgery for whom cardiopulmonary bypass was anticipated in a r and omized , single-blind , and controlled pilot trial . Patients were stratified for the type of surgery and equally assigned to a control group or to receive remote ischemic preconditioning by an automated thigh tourniquet consisting of three 5-min intervals of lower extremity ischemia separated by 5-min intervals of reperfusion . The primary end point was acute kidney injury defined as an elevation of serum creatinine of ≥0.3 mg/dl or ≥50 % within 48 h after surgery . Fifty-nine patients in each group were analyzed on an intention-to-treat basis . Acute kidney injury occurred in 12 remote ischemic preconditioned and 28 control patients , reflecting an absolute risk reduction of 0.27 and a significantly reduced relative risk due to preconditioning of 0.43 . Hence , remote ischemic preconditioning prevents acute kidney injury in patients undergoing cardiopulmonary bypass-assisted cardiac surgery Remote ischemic preconditioning ( RIPC ) with transient upper limb ischemia reduces myocardial injury in patients undergoing on-pump coronary artery bypass grafting ( CABG ) with cross-clamp fibrillation or blood cardioplegia for myocardial protection . Whether or not such protection is still operative when st and ard crystalloid cardioplegic arrest is used is uncertain . Fifty-three consecutive , non-diabetic patients with triple-vessel disease and 64 ± 12 years of age ( mean ± SD ) , who underwent elective CABG surgery with crystalloid ( Bretschneider ) cardioplegic arrest , were allocated in a prospect i ve , r and omized , single-blinded protocol to receive either a RIPC protocol ( 3 cycles of 5 min transient left upper arm ischemia induced by inflating a blood pressure cuff to 200 mmHg with 5 min of reperfusion ) or control , respectively , after induction of anesthesia . Cardiac troponin I ( cTnI ) concentration was measured preoperatively and over 72 h postoperatively , and the area under the curve ( AUC ) was calculated . Peak postoperative cTnI concentration was significantly reduced from 13.7 ± 7.7 ng/mL in controls to 8.9 ± 4.4 ng/mL in RIPC ( P = 0.008 ) . Mean cTnI concentration was significantly lower at 6 , 12 , 24 , and 48 h after surgery ( ANOVA ; P < 0.0001 ) in the RIPC patients ( N = 27 ) than in controls ( N = 26 ) , result ing in a 44.5 % reduction of cTnI ( AUC at 72 h ) . RIPC by repetitive inflation of a cuff around the left upper arm before surgery enhances myocardial protection in patients undergoing CABG surgery with ante grade cold crystalloid cardioplegia Perioperative and postoperative morbidity and mortality associated with cardiac surgery affect both the outcome and quality of life . Markers such as troponin effectively predict short-term outcome . In a prospect i ve cohort study in a University Hospital we assessed the role of cardiac biomarkers , also as predictors of long-term outcome and life quality after cardiac surgery with a three-year follow-up after conventional heart surgery . Patients were interviewed via phone calls with a structured question naire examining general health , functional status , activities of daily living , perception of life quality and need for hospital readmission . Descriptive statistics and multivariate analysis were performed . Out of 252 consecutive patients , 8 ( 3.2 % ) died at the three years follow up : 7 for cardiac complications and 1 for cancer . Thirty-six patients ( 13.5 % ) had hospital readmission for cardiac causes ( mostly for atrial fibrillation or other arrhythmias ( 9.3 % ) , but none needed cardiac surgical reintervention ; 21 patients ( 7.9 % ) were hospitalised for non-cardiac causes . No limitation in function activities of daily living was reported by most patients ( 94 % ) , 92 % perceived their general health as excellent , very good or good and none considered it insufficient ; 80 % were NYHA I , 17 % NYHA II , 3 % NYHA III and none NYHA IV . Multivariate analysis indicated preoperative treatment with digitalis or nitrates , and postoperative cardiac biomarkers release was independently associated to death . Elevated cardiac biomarker release and length of hospital stay were the only postoperative independent predictors of death in this study Objective To determine whether remote ischaemic preconditioning ( RIPC ) is cardioprotective in patients undergoing heart valve replacement . Design Single-blinded , r and omised controlled trial . Setting Tertiary referral hospital in China . Patients Adult patients ( 31–72 years ) undergoing mitral valve , aortic valve or tricuspid valve surgery . Interventions Patients were r and omised to either the RIPC ( n=38 ) or control ( n=35 ) group . After induction of anaesthesia , patients in the RIPC group underwent three 5 min cycles of right upper limb ischaemia , induced by an automated cuff-inflator placed on the upper arm and inflated to 200 mm Hg . Each cycle was interrupted by a 5 min period of reperfusion during which time the cuff was deflated . The control group had only a deflated cuff placed on the upper arm for 30 min . Main outcome measures Serum troponin I concentration was measured before surgery and at 6 , 12 , 24 , 48 , and 72 h postoperatively . The cardiac function of all patients was followed postoperatively . Results Troponin I concentration was reduced in the RIPC group ( 398.7±179.3 μg/l ) compared with the control group ( 708.4±242.5 μg/l ) . Mean difference was 309.7±50.8 ( 95 % CI 210.1 to 409.3 , p<0.0001 ) . A greater improvement in postsurgical cardiac function was noted in the RIPC group than in the control group . Conclusions These data indicate that RIPC reduces myocardial injury and improves cardiac function in patients undergoing heart valve surgery . Trial registration number NCT01175681 BACKGROUND Whether limb ischemic preconditioning ( LIPC ) is beneficial for patients undergoing mitral valve replacement ( MVR ) surgery is unknown . METHODS AND RESULTS Seventy-five adult patients undergoing MVR surgery were r and omly assigned to 3 groups : control group ( n=25 ) , LIPC group I ( 3 × 5-min cycles of right upper arm ischemia and 5-min reperfusion ; n=25 ) and LIPC group II ( 3 × 5-min cycles of right upper arm ischemia and 5-min reperfusion combined with 2 × 10-min cycles of right upper leg ischemia and 10-min reperfusion ; n=25 ) . Cardiopulmonary bypass ( CPB ) time , cross-clamp time , cardiac index , cumulative postoperative dosage of dobutamine , intensive care stay , postoperative hospital stay were not statistically different . Although the cumulative postoperative dosage of dobutamine was not different , there was a significantly lower inotropic requirement in LIPC II compared with the control group at 4 and 8h after surgery . Plasma levels of cardiac troponin-I in the 3 groups significantly increased during CPB and peaked at 4h after surgery . Levels of cTnI in LIPC II were significantly lower than in the control group at each time point after surgery . CONCLUSIONS Myocardial injury is obvious after MVR surgery . LIPC can protect the myocardium from ischemia-reperfusion injury and decrease the inotropic requirement after surgery . The data also confirmed the requirement for the preconditioning stimulus to cross a threshold OBJECTIVE To determine the role of remote ischemic pre-conditioning ( rIPC ) on myocardium , against ischemia reperfusion injury in patients undergoing coronary artery bypass graft ( CABG ) surgery by measuring CKMB levels . STUDY DESIGN A r and omized controlled trial . PLACE AND DURATION OF STUDY The Surgical Department of Armed Forces Institute of Cardiology/National Institute of Heart Diseases , Rawalpindi , from January to June 2008 . METHODOLOGY One hundred patients with double and triple vessels coronary artery disease were r and omized in two groups of 50 each . rIPC protocol consisted of 3 x 5 minutes of forearm ischemia , induced by a blood pressure cuff inflated to 200 mmHg , with an intervening 5 minutes of reperfusion , during which the cuff was deflated . Patients in the control group were not subjected to limb ischemia . The protocol of induced ischemia was completed before placing patients on extracorporeal bypass circuit . At the end of surgery serum CKMB levels were measured and compared at 8 , 16 , 24 and 48 hours from both the groups . Written informed consent was taken from patients . Study was approved by the hospital ethical committee . RESULTS Remote ischemic pre-conditioning significantly reduced CKMB levels at 8 , 16 , 24 and 48 hours after surgery with p-values of 0.026 , 0.021 , 0.052 and 0.003 respectively . There was mean reduction of 3 iu/l in CKMB levels , in patients who underwent rIPC protocol prior to CABG surgery , compared to control group . CONCLUSION This study showed a significant reduction of enzyme marker CKMB in patients subjected to rIPC prior to CABG surgery . This suggests lesser degree of myocardial damage compared to control group in CABG patients Perioperative myocardial ischemia contributes to postoperative morbidity and mortality . Remote intermittent ischemia ( RI ) has been shown to benefit patients undergoing coronary artery bypass graft ( CABG ) surgery by decreasing postoperative cardiac troponin levels . In addition , there is evidence that volatile anesthetics may provide myocardial protection . In this prospect i ve r and omized controlled trial we tested the hypothesis that RI is cardioprotective under a strict anesthetic regime with volatile anesthesia until cardiopulmonary bypass ( CPB ) . We also assessed whether RI modulates postoperative cytokine and growth factor concentrations . Fifty-four patients referred for elective CABG surgery without concomitant valve or aortic surgery were r and omized to three 5-min cycles of left upper limb ischemia by cuff inflation ( RI ) or placebo without cuff inflation ( Plac ) . All patients received the volatile anesthetic isoflurane ( 1.15–1.5 vol% ) before CPB and the intravenous anesthetic propofol ( 3–4 mg/kg/h ) thereafter until the end of surgery . Cardiac arrest during CPB was induced by intermittent cross-clamp fibrillation , or by blood cardioplegia . We excluded patients older than 85 years , with unstable angina , significant renal disease , and those taking sulfonylureas . Troponin I ( cTnI ) was measured preoperatively and after 6 , 12 , 24 and 48 h. In addition , brain natriuretic peptide ( BNP ) , creatine kinase ( CKMB ) and a panel of cytokines and growth factors were analyzed perioperatively . Although cTnI , BNP and CKMB all increased post-CABG , there were no significant differences between RI and Plac groups ; area under the curve for cTnI 189.4 ( 183.6 ) ng/mL/48 h and 183.0 ( 155.2 ) ng/mL/48 h mean ( SD ) , p = 0.90 , respectively , despite a tendency to a shorter ( p < 0.07 ) cross-clamp time in the treatment group . Similarly , there were no differences between groups in the central venous concentrations of numerous cytokines and growth factors . In patients undergoing CABG surgery RI does not provide myocardial protection under a strict anesthetic regime with volatile anesthesia until CPB , and RI was not associated with changes in cytokines The efficacy of remote ischemic preconditioning ( RIPC ) in high-risk cardiac surgery is uncertain . In this study , 96 adults undergoing high-risk cardiac surgery were r and omised to RIPC ( 3 cycles of 5 min of upper-limb ischemia induced by inflating a blood pressure cuff to 200 mmHg with 5 min of reperfusion ) or control . Main endpoints were plasma high-sensitivity troponin T ( hsTNT ) levels at 6 and 12 h , worst post-operative acute kidney injury ( AKI ) based on RIFLE criteria , and noradrenaline duration . hsTNT levels were log-normally distributed and higher with RIPC than control at 6-h post cross-clamp removal [ 810 ng/ml ( IQR 527–1,724 ) vs. 634 ng/ml ( 429–1,012 ) ; ratio of means 1.41 ( 99.17 % CI 0.92–2.17 ) ; P=0.04 ] and 12 h [ 742 ng/ml ( IQR 427–1,700 ) vs. 514 ng/ml ( IQR 356–833 ) ; ratio of means 1.56 ( 99.17 % CI 0.97–2.53 ) ; P=0.01 ] . After adjustment for baseline confounders , the ratio of means of hsTNT at 6 h was 1.23 ( 99.17 % CI 0.88–1.72 ; P=0.10 ) and at 12 h was 1.30 ( 99.17 % CI 0.92–1.84 ; P=0.05 ) . In the RIPC group , 35/48 ( 72.9 % ) had no AKI , 5/48 ( 10.4 % ) had AKI risk , and 8/48 ( 16.7 % ) had either renal injury or failure compared to the control group where 34/48 ( 70.8 % ) had no AKI , 7/48 ( 14.6 % ) had AKI risk , and 7/48 ( 14.6 % ) had renal injury or failure ( Chi-squared 0.41 ; two degrees of freedom ; P = 0.82 ) . RIPC increased post-operative duration of noradrenaline support [ 21 h ( IQR 7–45 ) vs. 9 h ( IQR 3–19 ) ; ratio of means 1.70 ( 99.17 % CI 0.86–3.34 ) ; P=0.04 ] . RIPC does not reduce hsTNT , AKI , or ICU-support requirements in high-risk cardiac surgery BACKGROUND Myocardial necrosis occurs frequently in elective percutaneous coronary intervention ( PCI ) and is associated with subsequent major adverse cardiovascular events ( MACEs ) . This study assessed the protective effect of remote ischemic preconditioning ( RIPC ) in patients undergoing successful drug-eluting stent implantation with normal baseline troponin values . METHODS We analyzed 205 participants with normal baseline troponin values undergoing successful coronary stent implantation . Subjects were r and omized to 2 groups : The RIPC group ( n = 101 ) , whose members received RIPC ( created by three 5-minute inflations of a pneumatic medical tourniquet cuff to 200 mm Hg around the upper arm , interspersed with 5-minute intervals of reperfusion ) < 2 hours before the PCI procedure , and the control group ( n = 104 ) . RESULTS The primary outcomes were high sensitive cardiac troponin I ( hscTnI ) levels and incidence of myocardial infa rct ion ( MI 4a , defined as hscTnI > 0.20 ng/mL ) at 16 hours after the PCI procedure . The median hscTnI at 16 hours after PCI was lower in the RIPC group compared with the unpreconditioned , control group ( 0.11 vs 0.21 ng/mL ; P < 0.01 ) . The incidence of MI 4a was lower in the RIPC group compared with the control group ( 39 % vs 54 % , P < 0.05 ) . Index of renal function showed no difference between the 2 groups at 16 hours after PCI ( P > 0.05 ) . CONCLUSION RIPC reduced post-PCI TnI release and incidence of MI 4a in patients undergoing elective coronary stent implantation OBJECTIVE Remote ischemic preconditioning ( RIPC ) exerts neuroprotective effects in models of cerebral ischemia-reperfusion injury . The authors tested the hypothesis that RIPC decreases the incidence of postoperative delirium and prevents deterioration of short-term postoperative cognitive function in isoflurane-fentanyl-anesthetized patients undergoing cardiac surgery using cardiopulmonary bypass ( CPB ) . DESIGN R and omized , blinded , single-center pilot investigation . SETTING Veterans Affairs Medical Center . PARTICIPANTS Thirty age- and education-matched men≥55 years of age undergoing elective coronary artery or valve surgery using CPB . Fifteen nonsurgical patients also were enrolled . INTERVENTIONS RIPC was produced after induction of anesthesia using 4 cycles of brief ( 5 minutes ) upper extremity ischemia ( tourniquet inflation to 200 mmHg ) interspersed with 5-minute periods of reperfusion ( tourniquet deflation ) . MEASUREMENTS AND MAIN RESULTS The Intensive Care Delirium Screening Checklist was used to assess delirium before and each day after surgery for as many as 5 consecutive days . Recent verbal and nonverbal memory and executive functions were assessed before and 1 week after surgery using a st and ard neuropsychometric test battery or at 1-week intervals in nonsurgical controls . The Geriatric Depression and the Hachinski Ischemia scales were used to identify the presence of clinical depression and vascular dementia , respectively . No differences in delirium scores were observed between RIPC and control groups ( p=0.54 ) . Baseline neurocognitive scores were similar in patients with versus without RIPC in all 3 cognitive domains . Significant declines in performance on 2 nonverbal memory tests ( figure reconstruction and delayed figure reproduction ; p=0.001 and p=0.003 , respectively ) and 1 verbal memory test ( delayed story recall ; p=0.0004 ) were observed 1 week after surgery in patients who were not treated with RIPC . There were no changes in performance of measures of executive function in this group . In contrast , performance on all cognitive tests was unchanged after compared with before surgery in patients receiving RIPC . At least a 1-st and ard deviation decline from baseline in cognitive performance was detected in figure reconstruction , delayed figure reproduction , immediate story recall , and delayed story recall in patients who were not exposed to RIPC . The incidence of at least a 1-st and ard deviation decline in neuropsychometric tests was observed in significantly fewer ( 1 v 9 ; p<0.0001 ) patients with versus without RIPC treatment based on composite Z-scores . Overall cognitive performance after surgery was better in patients treated with versus without RIPC ( p=0.002 ) . Clinical depression and vascular dementia were not detected in either group . CONCLUSION The results of this pilot investigation indicated that RIPC prevented deterioration of short-term postoperative cognitive function but were unable to detect any difference in delirium in isoflurane-fentanyl-anesthetized patients undergoing cardiac surgery using CPB Purpose The efficacy of myocardial conditioning strategies is compromised in patients with advanced age , diabetes , or low ejection fraction . We conducted a single-centre parallel-arm blinded r and omized-controlled trial to determine whether propofol provides perioperative myocardial protection . Methods Patients enrolled in this study were scheduled for primary aortocoronary bypass surgery utilizing normothermic cardiopulmonary bypass ( CPB ) with blood cardioplegia . The participants were stratified by diabetic status and left ventricular ejection fraction and r and omly assigned to receive either an elevated dose of propofol –previously associated with experimental cardioprotection– or an isoflurane preconditioning regime . The primary endpoint was the coronary sinus ( CS ) concentration of 15-F2t-isoprostane ( isoP ) . Secondary endpoints included in-hospital low cardiac output syndrome ( LCOS ) and major adverse cardiac events , 12- and 24-hr CS cardiac troponin I ( cTnI ) release , and myocardial B-cell lymphoma 2 ( Bcl-2 ) protein expression . Results Data were analyzed from 125 of 137 r and omized participants . Participants receiving propofol experienced a greater mean ( SD ) increase from baseline in CS 15-F2t-isoP levels compared with those receiving isoflurane [ 26.9 ( 10.9 ) pg·mL−1vs 12.1 ( 10.4 ) pg·mL−1 , respectively ; mean difference , 14.8 ; 95 % confidence interval ( CI ) , 11.0 to 18.6 ; P < 0.001 ] but a decreased incidence of LCOS ( 20.9 % vs 57.1 % , respectively ; relative risk [RR],0.37 ; 95 % CI , 0.22 to 0.62 ; P < 0.001 ) . The incidence of LCOS was similar between groups in participants without type 2 diabetes mellitus ( DM2 ) ( P = 0.382 ) but significantly decreased in the propofol DM2 subgroup compared with the isoflurane DM2 subgroup ( 17.9 % vs 70.3 % , respectively ; RR , 0.26 ; 95 % CI , 0.13 to 0.52 ; P < 0.001 ) . Propofol was associated with an increase in myocardial Bcl-2 protein expression ( P = 0.005 ) , a lower incidence of a CS cTnI threshold for myocardial infa rct ion ( P = 0.014 ) , and fewer heart failure events ( P < 0.001 ) . Conclusion Propofol may be a preemptive intraoperative cardioprotectant for patients with DM2 under conditions of normothermic CPB and blood cardioplegic arrest . The study is registered at www . clinical trials.gov ( NCT00734383 ) and www.controlled-trials.com ( IS RCT N70879185).RésuméObjectifL’efficacité des stratégies de conditionnement myocardique est compromise chez les patients âgés ainsi que chez ceux atteints de diabète ou présentant une fraction d’éjection faible . Nous avons réalisé une étude r and omisée contrôlée unicentrique à bras parallèles et en aveugle afin de déterminer si le propofol procurait une protection myocardique en période périopératoire . MéthodeLes patients enrôlés dans cette étude devaient subir une chirurgie de pontage aorto-coronarien primaire avec circulation extracorporelle ( CEC ) normothermique et cardioplégie sanguine . Les participants ont été stratifiés par statut diabétique et fraction d’éjection ventriculaire gauche , puis aléatoirement répartis en deux groupes , do nt l’un recevrait une dose élevée de propofol – un agent précédemment associé à une cardioprotection expérimentale – et l’autre un régime de préconditionnement à l’isoflurane . Le critère d’évaluation principal était la concentration dans le sinus coronaire ( SC ) de 15-F2t-isoprostane ( isoP ) . Les critères d’évaluation secondaires comprenaient la survenue d’un syndrome de bas débit cardiaque ( SBDC ) pendant le séjour hospitalier et les complications cardiaques majeures , la libération de troponine I cardiaque ( cTnI ) du SC à 12 et 24 h , et l’expression protéinique du lymphome 2 à cellules B ( Bcl-2 ) myocardique . RésultatsLes données de 125 des 137 patients r and omisés ont été analysées . Les participants ayant reçu du propofol ont subi une augmentation moyenne ( ÉT ) plus importante depuis les valeurs de base en matière de niveaux au SC de 15-F2t-isoP par rapport aux patients ayant reçu de l’isoflurane [ 26,9 ( 10,9 ) pg·mL−1vs 12,1 ( 10,4 ) pg·mL−1 , respectivement ; différence moyenne , 14,8 ; intervalle de confiance ( IC ) 95 % , 11,0 à 18,6 ; P < 0,001 ] , mais une incidence moindre de SBDC ( 20,9 % vs 57,1 % , respectivement ; risque relatif [ RR ] , 0,37 ; IC 95 % , 0,22 à 0,62 ; P < 0,001 ) . L’incidence de SBDC était semblable dans les deux groupes chez les participants qui n’étaient pas atteints de diabète de type 2 ( DT2 ) ( P = 0,382 ) , mais significativement réduite dans le sous-groupe DT2 propofol par rapport au sous-groupe DT2 isoflurane ( 17,9 % vs 70,3 % , respectivement ; RR , 0,26 ; IC 95 % , 0,13 à 0,52 ; P < 0,001 ) . Le propofol a été associé à une augmentation de l’expression protéinique du Bcl-2 myocardique ( P = 0,005 ) , une incidence moindre de seuil de cTnI du SC pour un infa rct us du myocarde ( P = 0,014 ) , et moins d’épisodes d’insuffisance cardiaque ( P < 0,001 ) . Conclusion Le propofol pourrait constituer un cardioprotecteur peropératoire préventif pour les patients atteints de DT2 sous CEC normothermique et en arrêt cardioplégique sanguin . Cette étude est enregistrée au www . clinical trials.gov ( NCT00734383 ) et au www.controlled-trials.com ( IS RCT N70879185 ) BACKGROUND Remote ischaemic preconditioning has been associated with reduced risk of myocardial injury after coronary artery bypass graft ( CABG ) surgery . We investigated the safety and efficacy of this procedure . METHODS Eligible patients were those scheduled to undergo elective isolated first-time CABG surgery under cold crystalloid cardioplegia and cardiopulmonary bypass at the West-German Heart Centre , Essen , Germany , between April , 2008 , and October , 2012 . Patients were prospect ively r and omised to receive remote ischaemic preconditioning ( three cycles of 5 min ischaemia and 5 min reperfusion in the left upper arm after induction of anaesthesia ) or no ischaemic preconditioning ( control ) . The primary endpoint was myocardial injury , as reflected by the geometric mean area under the curve ( AUC ) for perioperative concentrations of cardiac troponin I ( cTnI ) in serum in the first 72 h after CABG . Mortality was the main safety endpoint . Analysis was done in intention-to-treat and per- protocol population s. This trial is registered with Clinical Trials.gov , number NCT01406678 . FINDINGS 329 patients were enrolled . Baseline characteristics and perioperative data did not differ between groups . cTnI AUC was 266 ng/mL over 72 h ( 95 % CI 237 - 298 ) in the remote ischaemic preconditioning group and 321 ng/mL ( 287 - 360 ) in the control group . In the intention-to-treat population , the ratio of remote ischaemic preconditioning to control for cTnI AUC was 0·83 ( 95 % CI 0·70 - 0·97 , p=0·022 ) . cTnI release remained lower in the per- protocol analysis ( 0·79 , 0·66 - 0·94 , p=0·001 ) . All-cause mortality was assessed over 1·54 ( SD 1·22 ) years and was lower with remote ischaemic preconditioning than without ( ratio 0·27 , 95 % CI 0·08 - 0·98 , p=0·046 ) . INTERPRETATION Remote ischaemic preconditioning provided perioperative myocardial protection and improved the prognosis of patients undergoing elective CABG surgery . FUNDING German Research Foundation Abstract Objectives . Although remote ischemic preconditioning ( RIPC ) has shown favorable effects on ischemia – reperfusion injury , much remains unknown of its mechanisms and clinical significance . We hypothesized that RIPC would reduce the incidence of postoperative atrial fibrillation ( POAF ) following coronary artery bypass graft ( CABG ) surgery . In addition , we investigated whether RIPC could induce alterations of circulating microRNA in blood plasma . Design . This is a single-center , double-blind , r and omized controlled trial . 92 adult patients referred for first-time isolated CABG surgery were r and omly assigned to either RIPC ( n = 45 ) or control ( n = 47 ) . The RIPC-stimulus comprised three 5-min cycles of upper arm ischemia , induced by inflating a blood pressure cuff to 200 mmHg , with an intervening 5 min reperfusion . Heart rhythm was assessed by telemetry . MicroRNA expression was assessed in plasma by real-time polymerase chain reaction . Results . Of the 92 patients included in the study , 27 patients developed POAF ( 29 % ) . 17 of these patients belonged to the RIPC group ( 38 % ) , and 10 to the control group ( 21 % ) . There were no significant alterations of microRNA expression . Conclusions . We did not observe a reduced incidence of POAF by RIPC before CABG surgery . Larger multi-center studies may be necessary to further clarify this issue . Trial registration : Clinical Trials.gov identifier : NCT01740102 BACKGROUND Remote perconditioning has been proved to reduce myocardial infa rct ion and improve ventricular function in vivo . This study aims to determine the protection of remote perconditioning against cardiac reperfusion injury in patients undergoing valve replacement . METHODS Eighty-one patients admitted for selective valve replacement were divided into three groups r and omly . Control patients ( con . n = 27 ) underwent sham placement of the tourniquet around the right thigh without inflation ; the remote preconditioning group ( pre . n = 26 ) received three cycles of 4/4 min right lower limb ischemia and reperfusion after induction of anesthesia , the limb ischemia was induced by the tourniquet inflated to 600 mmHg ; the remote perconditioning group ( per . n = 28 ) received the same stimulus immediately after aortic cross-clamping . Venous blood sample s were obtained preoperatively , 5 min before declamping , 30 min , 4 , 12 , and 72 h after declamping for detecting troponin I ( cTnI ) concentration . The clinical data of inotrope requirement , drainage , ventilation . and intensive care time were routinely recorded . RESULTS The remote perconditioning group had significantly lower release of cTnI 5 min before declamping ( con . versus pre . versus per . , 0.15 ± 0.10 versus 0.13 ± 0.08 versus 0.10 ± 0.04 ng/mL , P = 0.050 ) and 30 min after declamping ( con . versus pre . versus per . , 0.40 ± 0.24 versus 0.41 ± 0.40 versus 0.24 ± 0.13 ng/mL , P = 0.043 ) . Less incidence of defibrillation were observed in the remote perconditioning groups . CONCLUSIONS Remote perconditioning , which is induced by transient lower limb ischemia after aortic cross-clamping , reduces myocardial injury over cardioplegia in adults undergoing selective valve replacement PURPOSE OF THE STUDY To evaluate the effects of remote ischemic preconditioning ( RIPC ) on the perioperative period in elective aortic valve replacement ( AVR ) along different anaesthesia techniques . MATERIAL S AND METHODS 48 patients aged 50 to 75 years ( 64 ( 56;69 ) ) which were scheduled for AVR due to aortic valve stenosis were included into the prospect i ve , r and omized study . Four groups were formed after r and omization : 1 ) RIPC applied during propofol anesthesia ( RIPCprop , n = 12 ) , 2 ) RIPC applied during sevoflurane anesthesia ( RIPCsevo , n = 12 ) , 3 ) propofol anesthesia without RIPC ( CONTROLprop , n = 12 ) , 4 ) sevoflurane anesthesia without RIPC ( CONTROLsevo , n = 12 ) . Groups were similar in baseline data of patients . RIPC protocol : three five-minutes episodes of simultaneous both lower limbs ischemia with five-minutes reperfusion intervals . Troponin I ( cTrI ) , interleukin-6 ( IL-6 ) , Interleukin-8 ( IL-8 ) and C-reactive protein ( CRP ) levels were assessed prior to induction of anesthesia , at 30 min , 6 , 12 , 24 and 48 hours after the cessation of CPB . Significant differences were assessed by the nonparametric Mann-Whitney and Fisher 's exact tests . Data are presented as : median ( 25th percentile , 75th percentile ) . RESULTS . Significant differences in cTnI were found between RIPCsevo and CONTROLsevo groups at 6 , 12 and 24 hours : 1.68 ( 1.28 , 2.09 ) ng/ml vs 3.66 ( 2.07 , 4.49 ) ng/ml , respectively at 6 hours ( p = 0.04 ) ; 1.89 ( 1.59 , 2.36 ) ng/ml vs 3.66 ( 2.91 , 5.64 ) ng/ml , respectively at 12 hours ( p = 0.001 ) ; 1.68 ( 1.55 ; 2.23 ) ng/ml vs 3.32 ( 2.10 ; 5.46 ) ng/ml , respectively at 24 hours ( p = 0.01 ) . There were no differences found in cTnI between RIPCprop and CONTROLprop groups during the whole study . There were no significant differences found in the levels of IL-6 and CRP between RIPC and control groups during the whole study Unexpectedly significant excess concentrations of IL-8 at 24 h were found when RIPC applied during sevoflurane anesthesia : 12.3 ( 10.6 , 14.4 ) pg/mL in RIPCsevo group vs 6.2 ( 4.8 , 11.1 ) pg/ml in CONTROLsevo group ( p = 0.02 ) . There was no paroxysmal atrial fibrillation ( AF ) after RIPC , and 5 cases were registered in the control groups ( p = 0.02 ) . No other significant differences in the clinical course of the postoperative period were found . CONCLUSIONS Cardioprotective effect of RIPC and its effect on systemic inflammatory response should be assessed in the selected anesthesia groups . RIPC on the background of sevoflurane anesthesia reduces myocardial injury during AVR . RIPC does not reduce the severity of the systemic inflammatory response after AVR . RIPC reduces the risk of AF after AVR BACKGROUND Whether remote ischaemic preconditioning , an intervention in which brief ischaemia of one tissue or organ protects remote organs from a sustained episode of ischaemia , is beneficial for patients undergoing coronary artery bypass graft surgery is unknown . We did a single-blinded r and omised controlled study to establish whether remote ischaemic preconditioning reduces myocardial injury in these patients . METHODS 57 adult patients undergoing elective coronary artery bypass graft surgery were r and omly assigned to either a remote ischaemic preconditioning group ( n=27 ) or to a control group ( n=30 ) after induction of anaesthesia . Remote ischaemic preconditioning consisted of three 5-min cycles of right upper limb ischaemia , induced by an automated cuff-inflator placed on the upper arm and inflated to 200 mm Hg , with an intervening 5 min of reperfusion during which the cuff was deflated . Serum troponin-T concentration was measured before surgery and at 6 , 12 , 24 , 48 , and 72 h after surgery . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00397163 . FINDINGS Remote ischaemic preconditioning significantly reduced overall serum troponin-T release at 6 , 12 , 24 , and 48 h after surgery . The total area under the curve was reduced by 43 % , from 36.12 microg/L ( SD 26.08 ) in the control group to 20.58 microg/L ( 9.58 ) in the remote ischaemic preconditioning group ( mean difference 15.55 [ SD 5.32 ] ; 95 % CI 4.88 - 26.21 ; p=0.005 ) . INTERPRETATION We have shown that adult patients undergoing elective coronary artery bypass graft surgery at a single tertiary centre could benefit from remote ischaemic preconditioning , using transient upper limb ischaemia OBJECTIVE Remote ischemic preconditioning protects the myocardium from ischemia/reperfusion injury . We recently identified protection by remote ischemic preconditioning to be associated with the activation of signal transducer and activator of transcription 5 in left ventricular biopsy specimens of patients undergoing coronary artery bypass grafting during isoflurane anesthesia . Because remote ischemic preconditioning did not protect the heart during propofol anesthesia , we hypothesized that propofol anesthesia interferes with signal transducer and activator of transcription 5 activation . METHODS In a r and omized , single-blind , placebo-controlled , prospect i ve study , we analyzed an array of established cardioprotective proteins during propofol anesthesia with or without remote ischemic preconditioning in 24 nondiabetic patients with 3-vessel coronary artery disease . RESULTS Remote ischemic preconditioning ( n = 12 ) compared with no remote ischemic preconditioning ( n = 12 ) failed to decrease the area under the troponin I time curve ( 273 ± 184 ng/mL × 72 hours vs 365 ± 301 ng/mL × 72 hours ; P = .374 ) . Although phosphorylation of several protein kinases was increased from baseline to reperfusion , signal transducer and activator of transcription 5 phosphorylation was not increased and was not different between the remote ischemic preconditioning and no remote ischemic preconditioning groups . CONCLUSIONS Remote ischemic preconditioning during propofol anesthesia did not evoke either signal transducer and activator of transcription 5 activation or cardioprotection , implying interaction of propofol with cardioprotective signaling upstream of signal transducer and activator of transcription 5 Remote ischaemic preconditioning ( RIPC ) gained attention as a possibility to reduce myocardial injury after a subsequent sustained episode of myocardial ischaemia . This prospect i ve r and omized study was carried out to assess whether RIPC reduces myocardial injury in coronary artery bypass grafting patients . Eighty patients were assigned to remote preconditioning or control treatment . Ischaemic preconditioning was induced by three 5-min cycles of upper limb ischaemia and reperfusion after anaesthesia induction . Haemodynamic and markers of myocardial damage were analysed preoperatively and over 48 h postoperatively . The cardiac index was higher immediately after remote preconditioning in the main group . There were no differences in other haemodynamic , troponin I and creatine kinase-MB concentrations at any time point between groups . Thus , short-term remote preconditioning improves haemodynamics and does not reduce myocardial injury after coronary artery bypass surgery . Further study of high-risk patients may be needed to fully evaluate the clinical effect of RIPC OBJECTIVE Acute kidney injury after cardiac surgery with cardiopulmonary bypass is closely related to systemic inflammatory reactions and oxidative stresses . Remote ischemic preconditioning is a systemic protective strategy whereby brief limb ischemia confers systemic protection against prolonged ischemia and inflammatory reactions in distant organs . This study investigated whether remote ischemic preconditioning provides systemic protective effect on kidneys that are not directly exposed to ischemia-reperfusion injury during complex valvular heart surgery . METHODS Seventy-six adult patients undergoing complex valvular heart surgery were r and omly assigned to either remote ischemic preconditioning group ( n = 38 ) or control group ( n = 38 ) . Remote ischemic preconditioning consisted of 3 10-minute cycles of lower limb ischemia and reperfusion with an automated cuff inflator . Primary end points were comparisons of biomarkers of renal injury including serum creatinine , cystatin C and neutrophil gelatinase-associated lipocalin , and incidence of acute kidney injury . Secondary end points were comparisons of myocardial enzyme release and pulmonary parameters . RESULTS There were no significant differences in serum levels of biomarkers of renal injury between groups throughout the study period . The incidence of acute kidney injury did not differ between groups . Creatine kinase isoenzyme MB at 24 hours after surgery was lower , and intensive care unit stay was shorter in the remote ischemic preconditioning group than in the control group . CONCLUSIONS In patients undergoing complex valvular heart surgery , remote ischemic preconditioning did not reduce degree of renal injury or incidence of acute kidney injury whereas it did reduce myocardial injury and intensive care unit stay |
718 | 27,446,871 | Conclusion . | Background .
Pancreatic enzyme supplementation is widely used to treat pain in patients with chronic pancreatitis , despite little evidence for efficacy .
We performed a systematic review of the literature and a meta- analysis to investigate its effectiveness . | In a double-blind study on 19 patients with the diagnosis of chronic pancreatitis , the effects of treatment with a granulated pancreatic enzyme preparation ( Pankreon ) were compared with those of placebo administration . One week of treatment with each preparation was preceded by one week without any medication . The patients kept daidy records of their symptoms , plotting the severity of pain on an analog scale . Weekly assessment s of the mean pain level were also made by an examiner question ing the patients . Recordings of body weights and pancreas and liver laboratory tests were done weekly . Fifteen of 19 patients noted less pain during the week of treatment with pancreatic enzymes as compared to that of placebo treatment ( P<0.05 ) . The average reduction of pain , as calculated for all patients , was 30 % as evaluated by both patients ( P<0.01 ) and the examiner ( P<0.05 ) . No differences were found in other parameters examined . A possible explanation of the findings could be an effect on the intraductal pressure by intraluminal trypsin BACKGROUND This study was aim ed to investigate the effect of long-term treatment with high-protease pancreatic extract on the recurrent abdominal pain of patients with chronic pancreatitis . METHODS Twenty-six patients with a firm diagnosis of chronic pancreatitis and a pattern of recurrent pain were recruited and r and omly assigned to treatment with pancreatic extract ( Pancrex-Duo capsules , each containing 34,375 USP units of protease in enteric-coated microspheres ) or placebo , at a dose of four capsules four times daily , for 4 months . At the end of the first period patients were switched to the other medication for the next 4 months . Four patients did not complete the study because of unbearable recurring pain or inadequate compliance with treatment . The other 22 patients daily recorded the presence , intensity , and duration of pain and the consumption of analgesics , for 8 months . RESULTS No difference was found when intraindividual records during placebo and extract treatment periods were compared . Conversely , in the second 4 months of follow-up , regardless of the treatment given in the first period , there was a significant reduction in the cumulative pain score ( median , 95 ; range , 0 - 1005 , versus 134 ; 0 - 972 ; p < 0.05 ) , in the number of days ( 8 ; 0 - 132 , versus 13 ; 0 - 126 ; p < 0.02 ) and hours ( 54 ; 0 - 680 , versus 80 ; 0 - 602 ; p < 0.05 ) of pain , and in the analgesic consumption score ( 0 ; 0 - 22 , versus 12 ; 0 - 44 ; p = 0.02 ) . CONCLUSIONS Chronic supplementation with pancreatic extract is not beneficial in the management of recurrent pain in patients with chronic pancreatitis Background Chronic pancreatitis often culminates in maldigestion and diabetes . Clinical management is complex as the correction of maldigestion often disturbs diabetic control . Study In the following study , we examined the effects of a potent new commercial pancreatic enzyme on food absorption and blood glucose control . Enzymes were manufactured in enteric-coated mini-microsphere form ( 0.7–1.6 mm ) , design ed to prevent gastric acid degradation and facilitate co-migration with food , and given in quantities calculated to cover normal digestion requirements ( four capsules with meals , two with snacks ; content/capsule : lipase 10,000 USP units , protease 37,500 units , amylase 33,200 units ) . Forty patients with chronic pancreatitis were screened during a run-in nonenzyme-supplemented phase ; only those with stool fat excretion rates over 10 g/d ( n = 29 ) were advanced to a 14-day parallel r and omized placebo versus enzyme supplement group comparison . Results Of these , 62 % were diabetic ( 50 % insulin-dependent ) and 52 % were malnourished ( body mass index less than 20 kg/m2 ) . After enzyme supplementation , stool fat and nitrogen excretion decreased , whereas fat absorption increased from 54.0 ± 9.7 % to 80.8 ± 3.8 % per day ( p = 0.002 ) and protein from 80.5 ± 3.4 % to 86.8 ± 2.2 % per day ( p = 0.004 ) . Changing treatment from active enzyme supplementation to placebo ( and vice versa ) result ed in major problems with glucose control ; blood glucose levels became abnormal in 28 of 29 patients , one patient required hospitalization for symptomatic hypoglycemia ( 0.9 mmol/L ) during placebo treatment , and one developed diabetic ketoacidosis after recommencing active enzyme supplementation . Conclusions In conclusion , high-dose pancreatin mini-microspheres improved , but did not normalize , fat absorption , possibly because of the residual influence of diabetes and malnutrition on absorptive function . In view of the brittle nature of blood glucose control in malnourished insulin-dependent patients , enzyme adjustment should be carefully supervised in-hospital According to the theory of negative feedback regulation of pancreatic enzyme secretion by proteases , treatment with pancreatic extracts has been proposed to lower pain in chronic pancreatitis by decreasing pancreatic duct pressure . We conducted a prospect i ve placebo-controlled double blind multicenter study to investigate the effect of porcine pancreatic extracts on pain in chronic pancreatitis . 47 patients with pain ( 41 males , 6 females ) due to chronic pancreatitis documented by sonography , endoscopic retro grade cholangiopancreatography , and CT were included . Exclusion criteria were steatorrhea above 30 g/day , gastric or pancreatic resections in the history , and serum bilirubin above 1.5 mg/dl . Patients received pancreatic extracts ( acid-protected microtablets ; Panzytrat -20,000 ; 5 x 2 capsules/day ; proteases/capsule 1,000 Pharmacopoea europaea units ) for 14 days followed by treatment with placebo for another 14 days or vice versa . Pain ( grade d from 0 to 3 ) and concomitant use of analgesics ( N-butylscopolaminiumbromide and tramadol ) were recorded by diary . Physical examination and blood chemistry were done at day -1 , 15 and 29 . Quantitative stool fat was determined at days -2/-1 , 13/14 and 27/28 . 43 patients completed the studies . Pain improved in most patients irrespective of whether they started with placebo or verum . There was no significant difference between both treatment arms . We conclude that pancreatic extracts are not very efficient in lowering pain The symptomatic effect of pancreatic enzyme substitution therapy was examined in a 4-week double-blind crossover study . Twenty patients , 11 with and 9 without steatorrhoea , were examined . Pancreatic steatorrhoea was reduced from a median of 24 g/day to 10 g/day by the enzyme therapy ( P less than 0.01 ) . No significant pain reduction was found in either of the two groups , although there was a tendency to reduction in pain and analgetic consumption in the patients with steatorrhoea when treated with pancreatic enzymes . It is concluded that pancreatic steatorrhoea is still the only indication for pancreatic enzyme therapy |
719 | 27,179,544 | This might have implication s for the selection of patients for cardioprotection .
Despite common emphasis , diastolic functional abnormalities were infrequent in the long term .
A limited amount of data suggest that right ventricular dysfunction is important in this population . | BACKGROUND Chest irradiation is a commonly used treatment for malignancy , with demonstrated symptomatic and survival benefit .
The frequency and presentation of cardiovascular complications of radiotherapy remains unclear .
METHODS We performed a systematic review to evaluate the prevalence and manifestations of myocardial dysfunction ( asymptomatic and symptomatic ) in long-term cancer survivors treated with radiotherapy .
Although ejection fraction is often normal , systolic dysfunction has been more widely reported with modern techniques including 2-dimensional speckle strain and cardiac magnetic resonance . | BACKGROUND Radiotherapy for early breast cancer can decrease breast cancer mortality but increase other mortality , mainly from heart disease and lung cancer . The mean cardiac dose from irradiation of a left-sided breast cancer can be two or three times that for a right-sided breast cancer . The mean ipsilateral ( ie , on the same side as the breast cancer ) lung dose can also be two or three times the mean contralateral lung dose . Particularly during the 1970s , when typical heart and lung exposures were greater than now , the laterality of an irradiated breast cancer could measurably affect cardiac mortality and mortality from cancer of the right or the left lung decades later . This study aim ed to assess the hazards in the general US population from routine cancer-registry and death-certificate data . METHODS We analysed data for 308 861 US women with early breast cancer of known laterality ( left-sided or right-sided ) who were registered in the US Surveillance Epidemiology and End Results ( SEER ) cancer registries during 1973 - 2001 and followed prospect ively for cause-specific mortality until Jan 1 , 2002 . FINDINGS 115 165 ( 37 % ) received radiotherapy . Among those who did not , tumour laterality was of little relevance to subsequent mortality . For women diagnosed during 1973 - 82 and irradiated , the cardiac mortality ratio ( left versus right tumour laterality ) was 1.20 ( 95 % CI 1.04 - 1.38 ) less than 10 years afterwards , 1.42 ( 1.11 - 1.82 ) 10 - 14 years afterwards , and 1.58 ( 1.29 - 1.95 ) after 15 years or more ( trend : 2p=0.03 ) . For women diagnosed during 1983 - 92 and irradiated , the cardiac mortality ratio was 1.04 ( 0.91 - 1.18 ) less than 10 years afterwards and 1.27 ( 0.99 - 1.63 ) 10 or more years afterwards . For women diagnosed during 1993 - 2001 and irradiated the cardiac mortality ratio was 0.96 ( 0.82 - 1.12 ) , with none yet followed for 10 years . Among women irradiated for breast cancer who subsequently developed an ipsilateral or contralateral lung cancer , the lung cancer mortality ratio ( ipsilateral versus contralateral ) for women diagnosed during 1973 - 82 and irradiated was 1.17 ( 0.62 - 2.19 ) , 2.00 ( 1.00 - 4.00 ) , and 2.71 ( 1.65 - 4.48 ) , respectively , less than 10 years , 10 - 14 years , and 15 or more years afterwards ( trend : 2p=0.04 ) . For women irradiated after 1982 there is , as yet , little information on lung cancer risks more than 10 years afterwards . INTERPRETATION US breast cancer radiotherapy regimens of the 1970s and early 1980s appreciably increased mortality from heart disease and lung cancer 10 - 20 years afterwards with , as yet , little direct evidence on the hazards after more than 20 years . Since the early 1980s , improvements in radiotherapy planning should have reduced such risks , but the long-term hazards in the general population s of various countries still need to be monitored directly PURPOSE To study incidence of radiation-related heart disease in a large population of breast cancer patients followed for up to 30 years . MATERIAL AND METHODS 72,134 women diagnosed with breast cancer in Denmark or Sweden during 1976 - 2006 and followed prospect ively . Radiation-related risk was studied by comparing women with left-sided and right-sided tumours . RESULTS 34,825 women ( 48 % ) received radiotherapy . Among unirradiated women tumour laterality had little relevance to heart disease . Among irradiated women mean dose to the whole heart was 6.3 Gy for left-sided tumours and 2.7 Gy for right-sided tumours . Mortality was similar in irradiated women with left-sided and right-sided tumours , but incidence ratios , left-sided versus right-sided , were raised : acute myocardial infa rct ion 1.22 ( 95 % CI 1.06 - 1.42 ) , angina 1.25 ( 1.05 - 1.49 ) , pericarditis 1.61 ( 1.06 - 2.43 ) , valvular heart disease 1.54 ( 1.11 - 2.13 ) . Incidence ratios for all heart disease were as high for women irradiated since 1990 ( 1.09 [ 1.00 - 1.19 ] ) as for women irradiated during 1976 - 1989 ( 1.08 [ 0.99 - 1.17 ] ) , and were higher for women diagnosed with ischaemic heart disease prior to breast cancer than for other women ( 1.58 [ 1.19 - 2.10 ] versus 1.08 [ 1.01 - 1.15 ] , p for difference=0.01 ) . CONCLUSIONS Breast cancer radiotherapy has , at least until recently , increased the risk of developing ischaemic heart disease , pericarditis and valvular disease . Women with ischaemic heart disease before breast cancer diagnosis may have incurred higher risks than others CONTEXT Heart failure incidence increases with advancing age , and approximately half of patients with heart failure have preserved left ventricular ejection fraction . Although diastolic dysfunction plays a role in heart failure with preserved ejection fraction , little is known about age-dependent longitudinal changes in diastolic function in community population s. OBJECTIVE To measure changes in diastolic function over time and to determine the relationship between diastolic dysfunction and the risk of subsequent heart failure . DESIGN , SETTING , AND PARTICIPANTS Population -based cohort of participants enrolled in the Olmsted County Heart Function Study . R and omly selected participants 45 years or older ( N = 2042 ) underwent clinical evaluation , medical record abstract ion , and echocardiography ( examination 1 [ 1997 - 2000 ] ) . Diastolic left ventricular function was grade d as normal , mild , moderate , or severe by vali date d Doppler techniques . After 4 years , participants were invited to return for examination 2 ( 2001 - 2004 ) . The cohort of participants returning for examination 2 ( n = 1402 of 1960 surviving [ 72 % ] ) then underwent follow-up for ascertainment of new-onset heart failure ( 2004 - 2010 ) . MAIN OUTCOME MEASURES Change in diastolic function grade and incident heart failure . RESULTS During the 4 ( SD , 0.3 ) years between examinations 1 and 2 , diastolic dysfunction prevalence increased from 23.8 % ( 95 % confidence interval [ CI ] , 21.2%-26.4 % ) to 39.2 % ( 95 % CI , 36.3%-42.2 % ) ( P < .001 ) . Diastolic function grade worsened in 23.4 % ( 95 % CI , 20.9%-26.0 % ) of participants , was unchanged in 67.8 % ( 95 % CI , 64.8%-70.6 % ) , and improved in 8.8 % ( 95 % CI , 7.1%-10.5 % ) . Worsened diastolic dysfunction was associated with age 65 years or older ( odds ratio , 2.85 [ 95 % CI , 1.77 - 4.72 ] ) . During 6.3 ( SD , 2.3 ) years of additional follow-up , heart failure occurred in 2.6 % ( 95 % CI , 1.4%-3.8 % ) , 7.8 % ( 95 % CI , 5.8%-13.0 % ) , and 12.2 % ( 95 % CI , 8.5%-18.4 % ) of persons whose diastolic function normalized or remained normal , remained or progressed to mild dysfunction , or remained or progressed to moderate or severe dysfunction , respectively ( P < .001 ) . Diastolic dysfunction was associated with incident heart failure after adjustment for age , hypertension , diabetes , and coronary artery disease ( hazard ratio , 1.81 [ 95 % CI , 1.01 - 3.48 ] ) . CONCLUSIONS In a population -based cohort undergoing 4 years of follow-up , prevalence of diastolic dysfunction increased . Diastolic dysfunction was associated with development of heart failure during 6 years of subsequent follow-up PURPOSE To assess cardiac mortality , coronary artery disease , myocardial dysfunction , and valvular heart disease in women younger than 65 years of age , at least 10 years after adjuvant radiotherapy following mastectomy in early breast cancer . METHODS AND MATERIAL S Ninety women ( 45 - 64 years old ) with Stage II breast cancer without relapse , included in the South Sweden Breast Cancer Trial ( premenopausal arm ) , with or without adjuvant postoperative radiotherapy + /- cyclophosphamide were examined with myocardial scintigraphy and echocardiography/Doppler , 10 - 17 years after radiotherapy . Thirty-four patients had been irradiated for left-sided tumors , 33 for right-sided tumors , and 23 patients had not been treated with radiotherapy . The radiotherapy ( conventional roentgen , electron beams , and high-energy photon beams combined , in each patient ) included the chest wall and the regional lymph nodes , with a specified target dose of 38 - 48 Gy , administered in daily fractions of 1.9 - 2.4 Gy , 5 days/week . RESULTS No cardiac deaths were found among the original 275 patients r and omized to adjuvant therapy . In the 90 patients examined , abnormal findings were recorded for ECG ( 14 patients ) , exercise test ( 5 patients ) , myocardial scintigraphy ( 6 patients ) , thickening of valve cusps ( 14 patients ) , and mild valvular regurgitation ( 20 patients ) . All patients had normal systolic function . Diastolic dysfunction was observed in 6 patients ( abnormal relaxation in 4 patients and restrictive filling abnormality in 2 patients ) . Although no significant differences were found between the 3 study groups , there was a tendency to more abnormal findings after radiotherapy . CONCLUSION Women younger than 50 years of age at the time of adjuvant radiotherapy following mastectomy in early breast cancer , had no serious cardiac sequelae 13 years ( median ) later , despite partly old-fashioned radiation techniques We evaluated the long-term effects of combined modality therapy ( CMT ) with adriamycin , bleomycin , vinblastine , dacarbazine ( ABVD ) or mechlorethamine , vincristine , prednisone , procarbazine (MOPP)/ABVD plus adjuvant low-dose ( < 30 Gy ) involved-field radiation therapy ( LDRT ) on cardiac and pulmonary functions in adult patients with Hodgkin 's disease ( HD ) . Adjuvant LDRT ( mean dose , 2340 cGy ) to the mediastinum was administered to 24 patients after chemotherapy with MOPP/ABVD ( n = 10 ) and ABVD ( n = 14 ) . The mean doses of doxorubicin and bleomycin were 233 mg/m2 and 92 IU/m2 , respectively . Cardiac and pulmonary function tests were performed in all patients and , when available , were compared with pretreatment studies . After a median follow-up of 6.3 years , none of the patients had cardiac or pulmonary symptoms . A 4.7 % overall decrease in left ventricular ejection fraction ( LVEF ) was observed ( p = 0.03 ) , but only one patient had a mildly decreased LVEF ( 47 % ) . Diastolic function , LVEF , and left ventricular volume remained within the normal range in the other 23 patients . Mild pulmonary function study abnormalities occurred in 8 of 24 patients , 6 of whom were cigarette smokers . There were no significant changes in total lung capacity and forced vital capacity ( FVC ) values , but there was a 3 % overall decrease in FEV1/FVC ratio ( p = 0.05 ) . In adult patients with HD , adjuvant LDRT after chemotherapy with ABVD or MOPP/ABVD did not result in a significant incidence of permanent pulmonary or cardiac toxicity after more than 6.3 years of median follow-up . Further studies are warranted to fully evaluate the impact of such therapy on cardiopulmonary function Purpose Whereas earlier research focused on specific patient groups , this study assessed the risk of cardiovascular disease ( CVD ) in an unselected population curatively treated for breast cancer ( BC ) , compared with an age-matched r and om sample of controls . Methods Risks were determined in BC survivors and controls . CVD was divided into three categories : congestive heart failure , vascular cardiac diseases , and “ other ” cardiac diseases . Hazard ratios ( HRs ) and 95 % confidence intervals ( 95 % CI ) adjusted for age , CVD , and CVD risk factors at baseline were determined by Cox regression analyses . Results All 561 survivors of BC experienced surgery of whom 229 received (neo)adjuvant radiotherapy , 145 received chemotherapy ( with or without radiotherapy ) , and 187 received no adjuvant therapy . During follow-up ( median 9 ; range 5–57 years ) , CVD occurred in 176/561 ( 31 % ) survivors and in 398/1,635 ( 24 % ) controls . After radiotherapy , no increased risks of congestive heart failure ( HR 0.5 ; 95 % CI 0.2–1.8 ) , vascular cardiac diseases ( HR 1.1 ; 95 % CI 0.7–1.7 ) , or other cardiac diseases ( HR 1.3 ; 95 % CI 0.8–2.3 ) were found compared with controls . Similar results were found after chemotherapy for congestive heart failure ( HR 1.8 ; 95 % CI 0.6–5.8 ) , vascular cardiac diseases ( HR 1.1 ; 95 % CI 0.5–2.3 ) , and other cardiac diseases ( HR 1.2 ; 95 % CI 0.3–5.5 ) . Conclusions In an unselected population of BC survivors , no significant increased risk of CVD after radiotherapy and /or chemotherapy was found compared with controls . However , the HRs after chemotherapy were in-line with previous studies . Future studies should include more detailed information on treatment and more specific outcome measures Abstract The objectives of this study were to prospect ively screen a cohort of asymptomatic long-term survivors of Hodgkin lymphoma ( HL ) treated with chest irradiation for occult cardiovascular disease ( CVD ) , and correlate screen-detected disease with prospect ively measured cardiovascular risk factors ( CRFs ) . A total of 182 HL survivors treated with chest irradiation ( median follow-up time 14.8 years ) were enrolled and underwent prospect i ve CRF measurement and resting and stress echocardiography to assess coronary artery disease (CAD)/valve disease and left ventricular systolic dysfunction ( LVSD ) . Forty-seven ( 26 % ) patients had occult CAD/valve disease and /or LVSD . LVSD was not correlated with CRFs . Controlling for treatment factors , hypertension ( odds ratio [ OR ] = 3.0 ) and elevated high-sensitivity C-reactive protein ( hs-CRP ) ( OR = 2.7 ) increased the likelihood of occult CAD/valve disease . Risk of CAD/valve disease rose exponentially with increasing blood pressure ( BP ) values , even in the normal range . Our findings suggest that BP screening may be useful in determining those survivors at greatest risk for occult CVD PURPOSE To assess the cardiac side effects , primarily the occurrence of ischemic heart disease in symptom-free patients with early breast cancer treated with radiotherapy . METHODS AND MATERIAL S Thirty-seven survivors of a former r and omized study of early breast cancer were examined . Twenty patients irradiated pre- or postoperatively for left sided disease ( study group patients ) were compared with 17 controls who were either treated for right sided disease , or were nonirradiated patients . Radiotherapy was r and omized in the original study ; either tangential field 60Co , or electron-therapy was delivered . Echocardiography and bicycle ergometry stress test with 99mTc SestaMIBI myocardial perfusion scintigraphy were carried out and the patients ' major risk factors for ischemic heart disease were also listed . RESULTS Our results showed a significant difference between the scintigraphic findings of the two groups . Five of the 20 study group patients ( 25 % ) , while none of the 17 controls exhibited some kind of significant defects on scintigraphy , indicating ischemic heart disease ( p < 0.05 ) . No deterioration in left ventricular systolic and /or diastolic function could be detected by echocardiography . CONCLUSION Radiotherapy for left sided breast cancer with the mentioned treatment technique may present as an independent risk factor in the long-term development of ischemic heart disease , while left ventricular dysfunction could not be related to the previous irradiation . We emphasize the need to optimize adjuvant radiotherapy for early breast cancer by considering the dose both to the heart as well as the cancer Changes in the transverse heart diameter and cardiothoracic ratio were determined by comparing the pretreatment and last follow-up posteroanterior chest x-rays of 96 patients with stage I-III Hodgkin 's disease who had received radiation therapy ( RT ) to the mediastinum , with the same parameters observed in 20 similar patients whose mediastinum was not irradiated . A significantly higher proportion of patients who had received RT to the mediastinum had a decrease in transverse heart diameter and cardiothoracic ratio . Among patients presenting with a large mediastinal mass , these changes were more pronounced as compared to the other groups ; however , this difference was not of statistical significance . First-pass left ventricular ejection fraction ( LVEF ) performed with 99mTc pertechnetate ( obtained in 55 of these patients 30 - 120 months after RT to the mediastinum ) was compared with the LVEF of 20 normal controls . The control group had a significantly higher LVEF than the group of patients who had received RT to the mediastinum . No correlation was observed between changes in these parameters and the use of adjuvant , salvage , or no chemotherapy after mediastinal RT . None of these patients presented congestive heart failure or constrictive pericarditis , but our findings indicate a sub clinical cardiomyopathy in more than one-half of the patients who received RT to the mediastinum , suggesting that the incidence of heart damage after mediastinal RT might be higher than expected . Prospect i ve studies are necessary to eluci date the incidence and implication s of this potentially serious complication |
720 | 18,843,744 | Three trials showed no significant difference between relaxation and psychological treatment on clinician-rated depression at post intervention ( SMD 0.29 ( 95 % CI -0.18 to 0.75)).Inconsistent effects were found when comparing relaxation training to medication and there were few data available comparing relaxation with complementary and lifestyle treatments .
Relaxation techniques were more effective at reducing self-rated depressive symptoms than no or minimal treatment .
However , they were not as effective as psychological treatment . | BACKGROUND Many members of the public have negative attitudes towards antidepressants .
Psychological interventions are more acceptable but require considerable therapist training .
Acceptable psychological interventions that require less training and skill are needed to ensure increased uptake of intervention .
A potential intervention of this sort is relaxation techniques .
OBJECTIVES To determine whether relaxation techniques reduce depressive symptoms and improve response/remission . | This study represents a 2.25-year follow-up to a treatment study reported earlier ( McLean & Hakstian , 1979 ) in which 121 unipolar depressed out patients were treated by either ( a ) nondirective psychotherapy , ( b ) behavior therapy , ( c ) pharmacotherapy , or ( d ) relaxation therapy . A nondepressed , normal control group was evaluated on the same 28 measures and 6 intervals for contrast purpose s. Behavior therapy patients alone were significantly improved in the areas of mood , personal productivity , and social activity , relative to treatment control patients over the follow-up period . Also , twice as many behavior therapy patients ( i.e. , 64 % ) fell within one st and ard deviation of the normal , nondepressed control group distribution on depressed mood , compared with non-directive psychotherapy and pharmacotherapy patients , when scores were aggregated across the 6 assessment points Eighty-four depressed pregnant women were recruited during the second trimester of pregnancy and r and omly assigned to a massage therapy group , a progressive muscle relaxation group or a control group that received st and ard prenatal care alone . These groups were compared to each other and to a non-depressed group at the end of pregnancy . The massage therapy group participants received two 20 min therapy sessions by their significant others each week for 16 weeks of pregnancy , starting during the second trimester . The relaxation group provided themselves with progressive muscle relaxation sessions on the same time schedule . Immediately after the massage therapy sessions on the first and last days of the 16-week period the women reported lower levels of anxiety and depressed mood and less leg and back pain . By the end of the study the massage group had higher dopamine and serotonin levels and lower levels of cortisol and norepinephrine . These changes may have contributed to the reduced fetal activity and the better neonatal outcome for the massage group ( i.e. lesser incidence of prematurity and low birthweight ) , as well as their better performance on the Brazelton Neonatal Behavior Assessment . The data suggest that depressed pregnant women and their offspring can benefit from massage therapy Les auteurs ont trouve une efficacite semblable pour la therapie cognitivo-comportementale et pour la relaxation , dans le traitement de la depression chez Outcomes of seven treatment trials comparing cognitive behavioral therapy to treatment with tricyclic antidepressant medication in major depressive disorder have been quite similar to one another . This led us to question whether treatment outcome in time-limited studies reflected a unique effect of cognitive behavioral therapy . To test the uniqueness hypothesis , relaxation training , a nonpharmacologic , noncognitive treatment , was chosen as a comparison for cognitive behavioral therapy as well as drug therapy . Treatment duration was 16 weeks . The sample of 37 patients treated for major depressive disorder was less depressed than those previously studied . For both cognitive behavioral therapy and relaxation training , outcome of depression was superior to that of tricyclic antidepressant medication by endpoint analysis . The posttreatment scores on the Beck Depression Inventory of 82 % of the group receiving cognitive behavioral therapy improved to a Beck Depression Inventory score ≤9 which was not significantly greater than that for the group receiving relaxation training.(73 % ) , so a unique effect was not demonstrated for cognitive behavioral therapy . The outcome for tricyclic antidepressant medication ( 29 % improved to criteria ) was significantly worse than that for cognitive behavioral therapy . The patient 's pretreatment initial expectancy was not predictive BACKGROUND Season-related subsyndromal depressive symptoms during winter are common among population s at high latitudes . Both physical exercise and exposure to bright light can relieve the fatigue and downturn of mood associated with the shortening length of day . Serum cholesterol level may be related to changes in mood , but the evidence is contradictory . Our objective was to compare the effect of aerobic exercise with or without bright-light exposure on health-related quality of life , mood , and serum lipids in a sample of relatively healthy adult subjects . METHOD A r and omized controlled trial was conducted with subjects allocated to group aerobics training in a gym with bright light ( 2500 - 4000 lux ) ( N = 40 ) or normal illumination ( N = 42 ) or to relaxation/stretching sessions in bright light as a control group ( N = 42 ) twice a week for a period of 8 weeks . Changes in mood were recorded using question naires at the beginning of the study , at weeks 4 and 8 . and at follow-up 4 months after the study . A blood sample was drawn before and after the 8-week intervention to measure the concentrations of serum lipids . RESULTS Ninety-eight subjects completed the 8-week study . Both exercise and bright light effectively relieved depressive symptoms . Bright light reduced atypical depressive symptoms more than exercise ( p = .03 ) , based on the atypical symptoms subscore of the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorders Version Self-Rating Format . There were no significant differences between the study groups in the changes in serum lipid levels . CONCLUSION Bright light administered twice a week , alone or combined with physical exercise , seems to be a useful intervention for relieving seasonal mood slumps Fifty-three child and adolescent psychiatric patients with depressive disorders were r and omly allocated to brief cognitive-behaviour therapy ( CBT ) or to a control treatment , relaxation training . Forty-eight patients completed the treatment phase of the trial , which comprised 5 - 8 treatment sessions . Post-treatment assessment s showed a clear advantage of CBT over relaxation on measures of both depression and overall outcome . However , there were no significant differences between the treatments on comorbid anxiety and conduct symptoms . At follow-up , the differences between the groups were reduced , partly because of a high relapse rate in the DTP group and partly because subjects in the relaxation group continued to recover Recent studies have found that positive affect is associated with greater relative left frontal EEG activation and negative affect is associated with greater relative right frontal EEG activation . Further , chronically depressed adults typically display stable right frontal EEG activation . The present study investigated the effects of music on mood state and right frontal EEG activation associated with chronic depression . Fourteen chronically depressed female adolescents listened to rock music for a 23-minute session . These adolescents were compared with a control sample of chronically depressed female adolescents who were simply asked to sit and relax their minds and their muscles for the same time period . EEG was recorded during baseline , music , and postmusic for three minutes each , and saliva sample s were collected before and after the session to determine the effects of the music on stress hormone ( cortisol ) levels . No group differences or changes were noted for observed or reported mood state . However , cortisol levels decreased and relative right frontal activation was significantly attenuated during and after the music procedure . It was concluded that music had positive effects on the physiological and biochemical measures even though observed and self-reported mood did not change Background Combining bright light exposure and physical exercise may be an effective way of relieving depressive symptoms . However , relatively little is known about individual factors predicting either a good response or treatment failure . We explored background variables possibly explaining the individual variation in treatment response or failure in a r and omised trial . Methods Participants were volunteers of working-age , free from prior mental disorders and recruited via occupational health centres . The intervention was a r and omised 8-week trial with three groups : aerobics in bright light , aerobics in normal room lighting , and relaxation/stretching in bright light . Good response was defined as a 50 % decrease in the symptom score on either the Hamilton Depression Rating Scale ( HDRS ) or 8-item scale of atypical symptoms . Background variables for the analysis included sex , age , body-mass index , general health habits , seasonal pattern , and sleep disturbances . Results Complete data were received from 98 subjects ( 11 men , 87 women ) . Of them , 42 ( 5 men , 37 women ) were classified as responders on the HDRS . Overall , light had a significant effect on the number of responders , as assessed with the HDRS ( X2 = .02 ) . The number needed to treat ( NNT ) for light was 3.8 . Conclusions We investigated the effect of bright light and exercise on depressive symptoms . Problems with sleep , especially initial insomnia , may predict a good response to treatment using combined light and exercise . Bright light exposure and physical exercise , even in combination , seem to be well tolerated and effective on depressive symptoms BACKGROUND So-called atypical depressive symptoms ( carbohydrate craving , prolonged sleep , weight gain , increased appetite ) frequently emerge in association with low illumination to which people are ordinarily exposed indoors , or even outdoors at extreme latitudes in wintertime . Our objective was to analyse the effect of physical exercise alone or combined with bright light on mood and the health-related quality of life during winter . METHODS We carried out a r and omized controlled trial on 120 indoor employees in southern Finl and between November and January . The subjects were allocated to supervised fitness training under bright ( 2500 - 4000 lx ) or ordinary ( 400 - 600 lx ) light conditions in a gym 2 - 3 times weekly for 8 weeks , or supervised relaxation training once a week over the same period as active placebo . We collected question naire data on the changes in mood and health-related quality of life after 4 and 8 weeks of training , and after 4 months follow-up . RESULTS Fitness training in bright light result ed in greater relief from atypical depressive symptoms and more vitality than in ordinary room light . Compared with relaxation alone , the former regime improved general mental health and social functioning in addition to the improvement in depressive symptoms and vitality , whereas the latter only increased vitality . CONCLUSIONS Supervised physical exercise combined with exposure to bright light appears to be an effective intervention for improving mood and certain aspects of the health-related quality of life in wintertime . This effect appears unrelated to the history of season-dependent symptoms , being noticeable among healthy individuals The National Institute of Mental Health ( NIMH ) Treatment of Depression Collaborative Research Program ( Elkin et al. , Archives of General Psychiatry , 46 , 971 - 982 ; 1989 ) reported treatment-by-severity interactions favouring pharmacotherapy for more depressed out patients , on a minority of relevant comparisons . The present study reports secondary analyses from a similar , preexisting data set in which treatment-by-severity interactions are systematic ally investigated with depressed out patients treated either with nondirective psychotherapy , behaviour therapy , pharmacotherapy , or relaxation/placebo . Despite multiple severity measures and variable severity cut scores , no treatment was differentially effective in improving more severely depressed patients . Also , there was little difference across symptom severity levels in the proportions of recovered patients between treatment groups . Finally , dynamic cluster analysis demonstrated that the proportion of pharmacotherapy nonresponders ( 20 % ) did not differ from the proportion of nonresponders in behaviour therapy or placebo groups . It is concluded that this failure to replicate the NIMH trial findings can not be attributed to treatment differences , population s or statistical power . The suggestion that pharmacotherapy be the treatment of choice for more severely depressed out patients appears to be unjustified on the basis of available evidence Thirty-two depressed adolescent mothers received ten 30-minute sessions of massage therapy or relaxation therapy over a five-week period . Subjects were r and omly assigned to each group . Although both groups reported lower anxiety following their first and last therapy sessions , only the massage therapy group showed behavioral and stress hormone changes including a decrease in anxious behavior , pulse , and salivary cortisol levels . A decrease in urine cortisol levels suggested lower stress following the five-week period for the massage therapy group Objective : To evaluate the short-term effects of exercise in patients with major depression . Design : Prospect i ve , r and omised , controlled study . Setting : A university hospital . Patients : A consecutive series of 38 in patients with a major depression episode undergoing st and ard clinical antidepressant drug treatment . Interventions : Patients were r and omly assigned to an exercise ( walking , n = 20 ) or placebo ( low-intensity stretching and relaxation exercises , n = 18 ) group . Training was carried out for 10 days . Main outcome measurements : Severity of depression assessed with the Bech-Rafaelsen Melancholy Scale ( BRMS ) and the Center for Epidemiologic Studies Depression scale ( CES-D ) . Results : After 10 days , reduction of depression scores in the exercise group was significantly larger than in the placebo group ( BRMS : 36 % v 18 % ; CES-D : 41 % v 21 % ; p for both = 0.01 ) ; the proportion of patients with a clinical response ( reduction in the BRMS scores by more than six points ) was also larger for the exercise group ( 65 % v 22 % , p<0.01 ) . Conclusions : Endurance exercise may help to achieve substantial improvement in the mood of selected patients with major depression in a short time Treatment efficacy is typically evaluated by examining group means and pre-post change scores . Although informative , such analyses may obscure individual or subgroup differences in response ( outcome profiles ) . The present study used two different methods to define treatment outcome profiles -- rationally-derived criteria ( Frank et al. , Archives of General Psychiatry 48 , 851 - 855 , 1991 ) and dynamic clustering -- to evaluate four treatments of unipolar depression : behaviour therapy , amitriptyline , psychodynamic psychotherapy and relaxation training ( attention placebo ) . The profiling methods yielded similar results . Regardless of treatment , the majority of patients displayed either a recovery or nonremission outcome profile , with relatively few instances of remission followed by a recurrence of depression . These findings challenge the view that any of the treatments are associated with a strong tendency to relapse , at least over the 3-month follow-up period . To further characterize the major outcome profiles , discriminant analysis was performed . Results indicated that recovery and nonremission profiles differed in that the latter was associated with a longer and more severe index episode and greater neuroticism . A number of variables , including family history of depression and therapists ' prediction of outcome , failed to distinguish recovered from unremitted patients Alcoholics with depressive symptoms score > or = 10 on the Beck Depression Inventory ( A.T. Beck , C. H. Ward , M. Mendelson , J. Mock , & J. Erbaugh , 1961 ) received 8 individual sessions of cognitive-behavioral treatment for depression ( CBT-D , n = 19 ) or a relaxation training control ( RTC ; n = 16 ) plus st and ard alcohol treatment . CBT-D patients had greater reductions in somatic depressive symptoms and depressed and anxious mood than RTC patients during treatment . Patients receiving CBT-D had a greater percentage of days abstinent but not greater overall abstinence or fewer drinks per day during the first 3-month follow-up . However , between the 3- and 6-month follow-ups , CBT-D patients had significantly better alcohol use outcomes on total abstinence ( 47 % vs. 13 % ) , percent days abstinent ( 90.5 % vs. 68.3 % ) , and drinks per day ( 0.46 vs. 5.71 ) . Theoretical and clinical implication s of using CBT-D in alcohol treatment are discussed Work in 1985 by Simons , Lustman , Wetzel , and Murphy showed that a patient 's score on Rosenbaum 's self-control scale predicted differential response to treatments for depression , with a high score predicting a good outcome with talking therapy and a low score a good outcome with drug therapy . This study of 37 patients did not replicate those findings . Using the same paradigm , we predicted response correctly 7 times and incorrectly 16 times , a clear failure . A valid method for choosing the best treatment for a patient with major depression remains to be found The effects of yoga and ayurveda on geriatric depression were evaluated in 69 persons older than 60 who were living in a residential home . Participants were stratified by age and gender and r and omly allocated to three groups : Yoga , Ayurveda , or Wait-list Control . The 15-item Geriatric Depression Scale was used to assess depressive symptoms prior to the intervention , and after 3 months and 6 months post-intervention . Participation in one of the three groups lasted 24 weeks . The yoga program ( 7 hours 30 minutes per week ) included physical postures , relaxation techniques , regulated breathing , devotional songs , and lectures . The Ayurveda Group received an herbal preparation twice daily for the whole period . The depression symptom scores of the Yoga Group at both 3 and 6 months decreased significantly , from a group average baseline of 10.6 to 8.1 and 6.7 , respectively ( p < .001 , paired t-test ) . The other groups showed no change . Hence , an integrated approach of yoga including the mental and philosophical aspects in addition to the physical practice s was useful for institutionalized older persons Objective To examine the effect of counselling and relaxation intervention on psychological symptoms in patients with gynaecological cancer between the post‐operative period and the six‐week review A community-based nursing study was conducted in Sydney , Australia , to compare the effects of progressive muscle relaxation and guided imagery on anxiety , depression , and quality of life in people with advanced cancer . In this study , 56 people with advanced cancer who were experiencing anxiety and depression were r and omly assigned to 1 of 4 treatment conditions : ( 1 ) progressive muscle relaxation training , ( 2 ) guided imagery training , ( 3 ) both of these treatments , and ( 4 ) control group . Subjects were tested before and after learning muscle relaxation and guided imagery techniques for anxiety , depression , and quality of life using the Hospital Anxiety and Depression scale and the Functional Living Index — Cancer scale . There was no significant improvement for anxiety ; however , significant positive changes occurred for depression and quality of life BACKGROUND In western countries , the yearly incidence of depression is estimated to be 3 - 5 % and the lifetime prevalence is 17 % . In patient population s with chronic diseases the point prevalence may be 20 % . Depression is associated with increased risk for various conditions such as osteoporoses , cardiovascular diseases , and dementia . WHO stated in 2000 that depression was the fourth leading cause of disease burden in terms of disability . In 2000 the cost of depression in the US was estimated to 83 billion dollars . A predominance of trials suggests that physical exercise has a positive effect on depressive symptoms . However , a meta- analysis from 2001 stated : " The effectiveness of exercise in reducing symptoms of depression can not be determined because of a lack of good quality research on clinical population s with adequate follow-up . " OBJECTIVES The major objective for this r and omized trial is to compare the effect of non-aerobic , aerobic , and relaxation training on depressive symptoms using the blindly assessed Hamilton depression scale ( HAM-D(17 ) ) as primary outcome . The secondary outcome is the effect of the intervention on working status ( i.e. , lost days from work , employed/unemployed ) and the tertiary outcomes consist of biological responses . DESIGN The trial is design ed as a r and omized , parallel-group , observer-blinded clinical trial . Patients are recruited through general practitioners and psychiatrist and r and omized to three different interventions : 1 ) non-aerobic , -- progressive resistance training , 2 ) aerobic training , -- cardio respiratory fitness , and 3 ) relaxation training with minimal impact on strength or cardio respiratory fitness . Training for all three groups takes place twice a week for 4 months . Evaluation of patients ' symptoms takes place four and 12 months after inclusion . The trial is design ed to include 45 patients in each group . Statistical analysis will be done as intention to treat ( all r and omized patients ) . Results from the DEMO trial will be reported according to the CONSORT guidelines in 2008 - 2009 Forty-three depressed women were r and omly assigned to either ( a ) an aerobic exercise treatment condition in which they participated in strenuous exercise , ( b ) a placebo treatment condition in which they practice d relaxation exercises , or ( c ) a no-treatment condition . Aerobic capacity was assessed before and after the 10-week treatment period . Self-reported depression was assessed before , during , and after the treatment period . The results indicated that subjects in the aerobic exercise condition evidence d reliably greater improvements in aerobic capacity than did the subjects in either of the other conditions ( p less than .002 in both cases ) and that the subjects in the aerobic exercise condition evidence d reliably greater decreases in depression than did subjects in the placebo condition ( p = .05 ) or subjects in the no-treatment condition ( p = .001 ) . These results provide the first controlled evidence concerning the effects of strenuous exercise on depression |
721 | 17,533,647 | All concluded that SCG was ineffective in paediatric asthma .
Rather than having no effect , it is demonstrated that a considerable body of evidence favours SCG compared to placebo and , far from being ineffective , the drug appears to be effective particularly in older children . | Sodium cromoglicate ( SCG ) has been available since around 1970 for the treatment of asthma and other allergic disorders in both adults and children .
It has been approved for use around the world .
Over the period of its development , a number of different formulations were introduced .
In 1999 , a systematic review of SCG use in childhood asthma was carried out and reported initially as a poster . | The results are reported here of a long-term double-blind controlled clinical trial of disodium cromoglycate ( D.S.C.G. ) and isoprenaline , D.S.C.G. alone , isoprenaline alone , and a placebo given as a powder for inhalation in the treatment of severe bronchial asthma . At the end of one year 16 out of 20 patients on D.S.C.G.-isoprenaline remained on the allocated capsules , compared with 10 out of 15 on D.S.C.G. , 5 out of 20 on isoprenaline , and 3 out of 19 taking the placebo . The differences between each of the D.S.C.G.-isoprenaline and D.S.C.G. regimens compared with the isoprenaline and placebo regimens were statistically significant . After eight weeks on four capsules a day the patients in each group were allocated at r and om so that half continued on full dosage and half on a reducing regimen . At the end of the year there was no significant difference in the failure rate between patients allocated the full dosage and the patients on the reducing dosage . The capsules were well tolerated and toxicity to D.S.C.G. was not observed BACKGROUND Inhalation therapy with sodium cromoglycate is recommended as the first-line prophylactic treatment for moderate asthma in children . The availability of spacer devices with face-masks has extended the applicability of metered-dose inhalers to younger children . We studied the feasibility and effects of this therapy compared with placebo in children aged 1 - 4 years . METHODS 218 children aged 1 - 4 years with moderate asthma were recruited through 151 general practitioners between March , 1995 , and March , 1996 . They were r and omly assigned sodium cromoglycate ( 10 mg three times daily ) or placebo , given by inhaler with spacer device and face-mask for 5 months . Rescue medication ( ipratropium plus fenoterol aerosol ) was available during the baseline period of 1 month and the intervention period . Parents completed a daily symptom-score list . The primary outcome measure was the proportion of symptom-free days in months 2 to 5 . Analysis was by both intention to treat and on treatment . FINDINGS 167 ( 77 % ) children completed the trial . 131 ( 78 % ) of these children used at least 80 % of the recommended dose . Of the 51 children who stopped prematurely , 23 had difficulties with inhaled treatment . The mean proportion of symptom-free days for both groups was greater for the treatment period than for the baseline period ( 95 % CI for mean difference 5.1 to 17.5 cromoglycate , 11.9 to 23.3 placebo ) . However there were no differences between the sodium cromoglycate and placebo groups in the proportion of symptom-free days ( mean 65.7 [ SD 25.3 ] vs 64.3 [24.5]% ; 95 % CI for difference -8.46 to 5.70 ) or in any other outcome measure . INTERPRETATION Our study in a general practice setting shows that inhalation therapy with a spacer device and face-mask is feasible in a majority of children below the age of 4 years . However , long-term prophylactic therapy with inhaled sodium cromoglycate is not more effective than placebo in this age-group Summary A double-blind , cross-over trial of disodium cromoglycate was carried out over a period of 6 weeks in 6 children and 4 adults . The reliability of symptomatic assessment was established by demonstrating concordance between four independent observers who rated symptoms on a notionally continuous scale . Significant clinical improvement was found during disodium cromoglycate therapy . This was not necessarily matched by improvement in the FEV in individual patients . The study is in general agreement with the reports of Howell and Altounyan ( 1967 ) , Kennedy ( 1967 ) , Smith and Devey ( 1968 ) and Moran et al. ( 1968 ) A previous investigation by Lambert et al. , which used computer simulation to examine the influence of choice of prior distribution on inferences from Bayesian r and om effects meta- analysis , is critically examined from a number of viewpoints . The practical example used is shown to be problematic . The various prior distributions are shown to be unreasonable in terms of what they imply about the joint distribution of the overall treatment effect and the r and om effects variance . An alternative form of prior distribution is tentatively proposed . Finally , some practical recommendations are made that stress the value both of fixed effect analyses and of frequentist approaches as well as various diagnostic investigations A double-blind , placebo-controlled study was performed to determine the efficacy and safety of cromolyn sodium ( Intal ) administered to children by metered dose inhaler ( MDI ) . Prior to entry , subjects were well controlled on cromolyn sodium capsules by Spinhaler turbo-inhaler plus beta 2 agonists . An active control interval of 2 weeks on cromolyn sodium capsules was followed by a 4-week single-blind period on placebo capsules . Those subjects whose asthma worsened significantly on placebo entered a 10-week double-blind phase , r and omized to receive either cromolyn sodium ( 2 mg per dose ) or placebo by MDI . Diary data , physician evaluation , and pulmonary function tests were used to assess efficacy , and scores were compared with the baseline value at 2-week intervals . Forty children with asthma , 8 to 20 years of age , entered the study and 32 qualified for the r and omized phase . No significant differences existed between the treatment groups at baseline . Most comparative data favored the cromolyn sodium group over the course of the study . Significant differences ( p less than .05 ) were noted for diary scores of breathlessness and overall asthma severity . There was significant improvement at the final visit favoring the cromolyn sodium group in restriction on normal activity , FEV1 , and PEFR . The cromolyn sodium group also experienced a decreasing need for concomitant bronchodilators . Both groups preferred pressurized aerosol by MDI over powdered capsules by Spinhaler . ( Intal and Spinhaler are registered trademarks of Fisons Corporation . Cromolyn sodium is a recently introduced drug used in the prophylactic treatment of severe , perennial , bronchial asthma , particularly in the pediatric age group . In a multicenter trial , 276 chronic asthmatic patients of eight pediatric allergists entered a r and omized , double-blind , placebo-controlled , crossover study lasting 12 weeks . Test compounds of cromolyn sodium or placebo were inhaled four times a day , and daily scores were kept of symptom severity as well as frequency of use of other medications . Patients had statistically significant lower average daily symptom scores when treated with cromolyn sodium as compared to treatment with placebo . A strong subjective preference for cromolyn sodium was expressed by 60 % of those completing the trial , versus 9 % for placebo . The patients ' need for other symptomatic medications also dropped significantly during the cromolyn treatment period Abstract A double-blind cross-over sequential trial of a new antiallergic compound , disodium cromoglycate ( ' FPL670 ' , ' Intal ' ) was carried out over a period of 6 weeks in ten patients severely disabled with allergic bronchial asthma . There was a significant clinical improvement during administration of FPL670 plus isoprenaline in all patients compared with two periods in which isoprenaline alone was given . Spirometric improvement occurred in only four patients . Subsequent experience over periods up to 26 months with these and other patients has confirmed the therapeutic value and safety of FPL670 in the management of allergic bronchial asthma A year-long double-blind trial was carried out in 53 asthmatic children with severe perennial symptoms who were not receiving corticosteroids or corticotrophin . The treatment group were given disodium cromoglycate with isoprenaline ( Intal Co. ) while the placebo group were given lactose with isoprenaline four times daily . The groups were closely matched for clinical , physiological , and immunological features . Evaluation was based on the use of a diary and clinical and physiological investigations , including exercise tests . After one year 71 % of the treatment group were still well controlled while 76 % of the placebo group had dropped out because of inadequate control of symptoms . There was no rise in the rate of failure towards the end of the trial period and there were no seasonal variations in the failure rate . No important toxic effects were noted . It was impossible to predict the outcome of the trial in any given patient from his clinical , physiological , or immunological status at the beginning . However , the prevention of exercise-induced asthma by premedication with disodium cromoglycate in a laboratory exercise test did correlate well with the satisfactory clinical response to the drug |
722 | 29,855,779 | Conclusions This meta- analysis shows that medication induces cortisol normalization effectively in a large percentage of patients . | Purpose To systematic ally review the effectiveness of medical treatment for Cushing ’s syndrome in clinical practice , regarding cortisol secretion , clinical symptom improvement , and quality of life .
To assess the occurrence of side effects of these medical therapies . | BACKGROUND Cushing 's disease is a rare debilitating endocrine disorder for which few prospect i ve interventional studies have been done . We report results of the first phase 3 trial assessing long-acting intramuscular pasireotide in patients with Cushing 's disease . METHODS In this phase 3 clinical trial we recruited patients aged 18 years or older with persistent , recurrent , or de-novo ( non-surgical c and i date s ) Cushing 's disease who had a mean urinary free cortisol ( mUFC ) concentration ( from three 24 h sample s ) of 1·5 - 5·0 times the upper limit of normal ( ULN ) , a normal or greater than normal morning plasma adrenocorticotropic hormone concentration , and a pituitary source of Cushing 's syndrome , from 57 sites across 19 countries . Exclusion criteria included previous pasireotide treatment , mitotane therapy within 6 months , and pituitary irradiation within 10 years . We r and omly allocated patients 1:1 ( block size of four ) using an interactive-response-technology system to intramuscular pasireotide 10 mg or 30 mg every 4 weeks for 12 months ( in the core phase ) . We stratified r and omisation by screening mUFC concentration ( 1·5 to < 2·0 × ULN and 2·0 - 5·0 × ULN ) . The dose could be uptitrated ( from 10 mg to 30 mg or from 30 mg to 40 mg ) at month 4 if the mUFC concentration was greater than 1·5 × ULN , and at month 7 , month 9 , or month 12 if the mUFC concentration was greater than 1·0 × ULN . Investigators , patients , site personnel , and those assessing outcomes were masked to dose group allocation . The primary endpoint was the proportion of patients in each group with an mUFC concentration of less than or equal to the ULN at month 7 . Efficacy analyses were based on intention to treat . This trial is registered with Clinical Trials.gov , number NCT01374906 . FINDINGS Between Dec 28 , 2011 , and Dec 9 , 2014 , we r and omly allocated 150 patients to receive pasireotide 10 mg ( 74 [ 49 % ] patients ) or 30 mg ( 76 [ 51 % ] patients ) . The primary efficacy endpoint was met by 31 ( 41·9 % [ 95 % CI 30·5 - 53·9 ] ) of 74 patients in the 10 mg group and 31 ( 40·8 % [ 29·7 - 52·7 ] ) of 76 in the 30 mg group . The most common adverse events were hyperglycaemia ( 36 [ 49 % ] in the 10 mg group and 36 [ 47 % ] in the 30 mg group ) , diarrhoea ( 26 [ 35 % ] and 33 [ 43 % ] ) , cholelithiasis ( 15 [ 20 % ] and 34 [ 45 % ] ) , diabetes mellitus ( 14 [ 19 % ] and 18 [ 24 % ] ) , and nausea ( 15 [ 20 % ] and 16 [ 21 % ] ) . Serious adverse events suspected to be study drug related were reported in eight ( 11 % ) patients in the 10 mg group and four ( 5 % ) in the 30 mg group . Two ( 3 % ) patients in the 30 mg group died during the study ( pulmonary artery thrombosis and cardiorespiratory failure ) ; neither death was judged to be related to the study drug . INTERPRETATION Long-acting pasireotide normalised mUFC concentration in about 40 % of patients with Cushing 's disease at month 7 and had a similar safety profile to that of twice-daily subcutaneous pasireotide . Long-acting pasireotide is an efficacious treatment option for some patients with Cushing 's disease who have persistent or recurrent disease after initial surgery or are not surgical c and i date s , and provides a convenient monthly administration schedule . FUNDING Novartis Pharma AG BACKGROUND Cabergoline is a long-acting dopamine receptor agonist used to treat prolactinomas . Identification of D(2 ) receptors in corticotroph tumors led to clinical trials of cabergoline therapy in limited cases of Nelson 's syndrome , ectopic ACTH-secreting tumors , and recently Cushing 's disease ( CD ) . OBJECTIVE To evaluate the long-term efficacy of cabergoline monotherapy in patients with CD . METHODS Retrospective analysis of non-r and omized clinical therapy with cabergoline in 30 patients with CD treated in academic centers of Buenos Aires and Montreal . Cabergoline was initiated at 0.5 - 1.0 mg/week and adjusted up to a maximal dose of 6 mg/week based on urinary free cortisol ( UFC ) levels . Complete response to cabergoline was defined as a sustained normalization of UFC with at least two normal values measured at 1 - 3 months interval ; partial response was defined as a decrease of UFC to < 125 % of the upper limit of normal , and treatment failure as UFC ≥ 125 % of it . RESULTS Within 3 - 6 months , complete response was achieved in 11 patients ( 36.6 % ) and partial response in 4 patients ( 13.3 % ) . After long-term therapy , nine patients ( 30 % ) remain with a complete response after a mean of 37 months ( range from 12 to 60 months ) with a mean dose of 2.1 mg/week of cabergoline . Two patients escaped after 2 and 5 years of complete response , but one patient transiently renormalized UFC after an increase in cabergoline dosage . No long-term response was maintained in four initial partial responders . CONCLUSIONS Cabergoline monotherapy can provide an effective long-term medical therapy for selected patients with CD , but requires close follow-up for dose adjustments Cushing 's syndrome ( CS ) is a serious condition requiring drug management in diverse clinical setting s. Fifty four patients ( 44 females , 10 males ) with CS , aged 14 - 63 , received ketoconazole ( KTZ ) prior to surgery ( n= 27 ) , as complementary therapy after surgery and /or radiotherapy ( n= 16 ) , or as primary treatment ( n= 11 ) . It was given at a 600 ( 500 - 600 ) mg/day ( median - Cl195 ) maintenance dose for periods ranging from 15 days to 13 years . Clinical signs , hepatic enzymes and urinary free cortisol ( UFC ) were evaluated before and during KTZ treatment . UFC normalised or decreased to subnormal values in 85 % of the patients , in 5 to 150 days after starting treatment ; although failing to normalise , UFC decreased to 12 - 48 % of pre-treatment values in the remaining patients . Clinical signs improved throughout . Side effects were adrenal insufficiency ( 18.5 % ) , reversible hepatic toxicity ( 11 % ) , allergic skin rash ( 5.5 % ) and gastric intolerance ( 3.7 % ) ; in 11 % of patients , an " escape phenomenon " was observed . Twenty-four out of the total ( 44.4 % ) were treated for prolonged periods , from one up to 13 years . In conclusion , this study confirms that KTZ is an effective and generally well tolerated treatment for CS particularly : a ) shortly before surgery , b ) because of persistent hypercortisolism after surgery or awaiting the results of radiotherapy , c ) as a reasonable option in patients with CS of unknown aetiology and , d ) as long-term therapy in any case of unsolved hypercortisolism after failure of current treatments CONTEXT AND OBJECTIVE The role of cabergoline in Cushing 's disease ( CD ) remains controversial . The experience is limited to case reports and few open studies that report the effects determined after ≥1 month of treatment . In prolactinomas and dopamine-responsive GH-secreting tumours , effects of cabergoline are seen within days or weeks . Here , we search ed for short-term effects of cabergoline in CD . DESIGN Twenty patients ( 19 naïve and one recurrent ) were included in a prospect i ve study . Cabergoline was administered in increasing doses of 0.5 - 5 mg/week over 6 weeks . METHODS Urinary free cortisol ( UFC ) 24 h , morning cortisol and ACTH , and salivary cortisol at 0800 , 1600 and 2300 h were determined once weekly throughout . Diurnal curves ( six sample s ) of serum cortisol were measured at start and end . RESULTS At study end , the median cabergoline dose was 5 mg , range 2.5 - 5 mg/week . The prolactin levels , markers of compliance , were suppressed in all patients . During the treatment , hypercortisolism varied , gradual and dose-dependent reductions were not seen . Five patients had a > 50 % decrease of UFC , three had a > 50 % rise of UFC . Salivary cortisol at 2300 h showed a congruent > 50 % change with UFC in two of the five cases with decreased UFC , and in one of the three cases with increased UFC . One patient with decreases in both UFC and 2300 h salivary cortisol also had a reduction in diurnal serum cortisol during the course of the study . CONCLUSIONS Cabergoline seems to be of little value in the management of CD . Only one patient had a response-like pattern . Given the known variability of disease activity in CD , this might represent a chance finding Cushing ’s disease ( CD ) is associated with increased morbidity and mortality . Until now , no medical treatment has been shown to be totally satisfactory when administrated alone . This study aim ed to assess the effectiveness of cabergoline with added ketoconazole and of the same combination in reverse , using urinary free cortisol ( UFC ) and late night salivary cortisol ( LNSC ) levels as biochemical markers of the treatments ’ efficacy in CD patients . A prospect i ve analysis conducted on 14 patients ( f/m = 12/2 ; median age 52 , range 33–70 years ) divided into two groups : 6 patients initially treated with cabergoline for 4–6 months ( rising from 0.5–1 mg/week up to 3.0 mg/week ) , after which ketoconazole was added ( group A ) ; and 8 patients first took ketoconazole alone for 4–6 months ( rising from 200 mg/day to 600 mg/day ) , then cabergoline was added ( group B ) . Patients were compared with 14 age-matched patients in prolonged remission after effective neurosurgery for CD . The combination therapy led to UFC normalization in 79 % of patients with no differences between the groups ; only one patient failed to respond at all . Neither drug succeeded in controlling the disease when taken alone . LNSC dropped when compared to baseline levels , but not to a significant degree ( p = 0.06 ) , and it remained significantly higher than in controls ( p = 0.0006 ) . Associating cabergoline with ketoconazole may represent an effective second-line treatment , achieving a satisfactory reduction in UFC levels and clinical improvement . Although the combined treatment lowered patients ’ LNSC levels , they remained higher than normal , indicating a persistent sub clinical hypercortisolism ; the implication s of this condition need to be considered . No differences emerged between the two treatment schedules BACKGROUND Cushing 's disease is associated with high morbidity and mortality . Pasireotide , a potential therapy , has a unique , broad somatostatin-receptor-binding profile , with high binding affinity for somatostatin-receptor subtype 5 . METHODS In this double-blind , phase 3 study , we r and omly assigned 162 adults with Cushing 's disease and a urinary free cortisol level of at least 1.5 times the upper limit of the normal range to receive subcutaneous pasireotide at a dose of 600 μg ( 82 patients ) or 900 μg ( 80 patients ) twice daily . Patients with urinary free cortisol not exceeding 2 times the upper limit of the normal range and not exceeding the baseline level at month 3 continued to receive their r and omly assigned dose ; all others received an additional 300 μg twice daily . The primary end point was a urinary free cortisol level at or below the upper limit of the normal range at month 6 without an increased dose . Open-label treatment continued through month 12 . RESULTS Twelve of the 82 patients in the 600-μg group and 21 of the 80 patients in the 900-μg group met the primary end point . The median urinary free cortisol level decreased by approximately 50 % by month 2 and remained stable in both groups . A normal urinary free cortisol level was achieved more frequently in patients with baseline levels not exceeding 5 times the upper limit of the normal range than in patients with higher baseline levels . Serum and salivary cortisol and plasma corticotropin levels decreased , and clinical signs and symptoms of Cushing 's disease diminished . Pasireotide was associated with hyperglycemia-related adverse events in 118 of 162 patients ; other adverse events were similar to those associated with other somatostatin analogues . Despite declines in cortisol levels , blood glucose and glycated hemoglobin levels increased soon after treatment initiation and then stabilized ; treatment with a glucose-lowering medication was initiated in 74 of 162 patients . CONCLUSIONS The significant decrease in cortisol levels in patients with Cushing 's disease who received pasireotide supports its potential use as a targeted treatment for corticotropin-secreting pituitary adenomas . ( Funded by Novartis Pharma ; Clinical Trials.gov number , NCT00434148 . ) CONTEXT There is currently no medical therapy for Cushing 's disease that targets the pituitary adenoma . Availability of such a medical therapy would be a valuable therapeutic option for the management of this disorder . OBJECTIVE Our objective was to evaluate the short-term efficacy of the novel multireceptor lig and somatostatin analog pasireotide in patients with de novo , persistent , or recurrent Cushing 's disease . DESIGN We conducted a phase II , proof-of-concept , open-label , single-arm , 15-d multicenter study . PATIENTS Thirty-nine patients with either de novo Cushing 's disease who were c and i date s for pituitary surgery or with persistent or recurrent Cushing 's disease after surgery without having received prior pituitary irradiation . INTERVENTION Patients self-administered sc pasireotide 600 microg twice daily for 15 d. MAIN OUTCOME MEASURE Normalization of urinary free cortisol ( UFC ) levels after 15 d treatment was the main outcome measure . RESULTS Of the 29 patients in the primary efficacy analysis , 22 ( 76 % ) showed a reduction in UFC levels , of whom five ( 17 % ) had normal UFC levels ( responders ) , after 15 d of treatment with pasireotide . Serum cortisol levels and plasma ACTH levels were also reduced . Steady-state plasma concentrations of pasireotide were achieved within 5 d of treatment . Responders appeared to have higher pasireotide exposure than nonresponders . CONCLUSIONS Pasireotide produced a decrease in UFC levels in 76 % of patients with Cushing 's disease during the treatment period of 15 d , with direct effects on ACTH release . These results suggest that pasireotide holds promise as an effective medical treatment for this disorder |
723 | 30,311,641 | The oral derivative capecitabine has practical advantages over 5-fluorouracil , with equal efficacy , but the addition of a second chemotherapeutic agent has yet to show a consistent significant efficacy benefit in r and omized clinical assessment . | BACKGROUND With the well established shift to neoadjuvant treatment for locally advanced rectal cancer , there is increasing focus on the use of radiosensitizers to improve the efficacy and tolerability of radiotherapy .
There currently exist few r and omized data exploring novel radiosensitizers to improve response and it is unclear what the clinical endpoints of such trials should be .
Neoadjuvant radiosensitization for locally advanced rectal cancer using fluoropyrimidine-based chemotherapy remains the st and ard of treatment . | BACKGROUND / AIM To investigate the feasibility and safety of preoperative capecitabine , cetuximab and radiation in patients with MRI-defined locally advanced rectal cancer ( LARC , cT3/T4 ) . PATIENTS AND METHODS 31 patients with LARC were treated with cetuximab and capecitabine concomitantly with 45 Gy radiotherapy and resected by total mesorectal excision . Histopathological response and association with KRAS status was evaluated . RESULTS R0-resection was possible in 27 of 31 ( 86 % ) patients . No complete pathological remission was observed . Radiochemotherapy with capecitabine and cetuximab was safe to administer and diarrhea was the main toxicity . KRAS-status did not correlate to down-staging or pathological response concerning T- or N-stage . CONCLUSION Neoadjuvant therapy with capecitabine and cetuximab in combination with radiotherapy did not lead to complete pathological remission . Treatment tolerability was excellent and toxicity remained low . KRAS status did not influence treatment outcomes . Capecitabine in combination with radiotherapy remains a st and ard therapy for locally advanced rectal cancer Background We investigated tumor regression grading ( TRG ) as a prognostic marker and individual-level surrogate for disease-free survival ( DFS ) in patients with rectal carcinoma treated within the Chirurgische Arbeitsgemeinschaft fur Onkologie/Arbeitsgemeinschaft Radiologische Onkologie/Arbeitsgemeinschaft Internistische Onkologie (CAO/ARO/AIO)-04 r and omized trial . Methods TRG was recorded prospect ively using the Dworak classification in 1179 patients after preoperative fluorouracil-based chemoradiotherapy ( CRT ) with or without oxaliplatin . Multivariable analysis was performed using Cox regression models adjusted for treatment arm , resection status , and pathologic stage . Individual-level surrogacy of TRG for DFS was examined using the four Prentice criteria ( PC1 - 4 ) . All statistical tests were two-sided . Results With a median follow-up of 50 months , the addition of oxaliplatin to fluorouracil-based CRT led to statistically significantly improved three-year DFS ( 75.9 % , 95 % CI = 72.3 to 79.5 , vs 71.3 % , 95 % CI = 67.6 to 74.9 , P = .04 , PC 1 ) and a shift toward more advanced TRG groups ( P < .001 , PC 2 ) compared with CRT with fluorouracil alone . The three-year DFS was 64.6 % ( 95 % CI = 57.3 to 71.9 ) , 77.6 % ( 95 % CI = 74.5 to 80.7 ) , and 92.3 % ( 95 % CI = 88.4 to 96.2 ) for TRG 0 + 1 ( poor regression ) , TRG 2 + 3 ( intermediate regression ) , and TRG 4 ( complete regression ) , respectively ( P < .001 , PC 3 ) . TRG constituted an independent prognostic factor for DFS ( TRG 2 + 3 vs TRG 0 + 1 , HR = 0.68 , 95 % CI = 0.51 to 0.90 , P = .007 ) . Due to multicollinearity , TRG 4 and pathologic stage could not be tested within the same model . The treatment effect on DFS was captured by TRG , satisfying individual-level PC4 . Conclusions Higher TRG after preoperative CRT predicted a favorable long-term outcome . At the individual patient level , TRG was a surrogate marker for DFS . Further phase III trials are needed to vali date TRG as a surrogate at trial level BACKGROUND PARP inhibitors are currently evaluated in combination with radiotherapy and /or chemotherapy . As sensitizers , PARP inhibitors are active at very low concentrations therefore requiring highly sensitive pharmacodynamic ( PD ) assays . Current clinical PD-assays partly fail to provide such sensitivities . The aim of our study was to enable sensitive PD evaluation of PARP inhibitors for clinical sensitizer development . MATERIAL AND METHODS P BMC s of healthy individuals and of olaparib and radiotherapy treated lung cancer patients were collected for ELISA-based PD-assays . RESULTS PAR-signal amplification by ex vivo irradiation enabled an extended quantification range for PARP inhibitory activities after ex vivo treatment with inhibitors . This " radiation-enhanced-PAR " ( REP ) assay provided accurate IC50 values thereby also revealing differences among healthy individuals . Implemented in clinical radiotherapy combination Phase I trials , the REP-assay showed sensitive detection of PARP inhibition in patients treated with olaparib and establishes strong PARP inhibitory activities at low daily doses . CONCLUSIONS Combination trials of radiotherapy and novel targeted agent(s ) often require different and more sensitive PD assessment s than in the monotherapy setting . This study shows the benefit and relevance of sensitive and adapted PD-assays for such combination purpose s and provides proof of clinical ly relevant cellular PARP inhibitory activities at low daily olaparib doses PURPOSE To assess the efficacy of 2 different approaches to neoadjuvant chemoradiation for distal rectal cancers . METHODS AND MATERIAL S One hundred six patients with T3/T4 distal rectal cancers were r and omized in a phase 2 study . Patients received either continuous venous infusion ( CVI ) of 5-Fluorouracil ( 5-FU ) , 225 mg/m(2 ) per day , 7 days per week plus pelvic hyperfractionated radiation ( HRT ) , 45.6 Gy at 1.2 Gy twice daily plus a boost of 9.6 to 14.4 Gy for T3 or T4 cancers ( Arm 1 ) , or CVI of 5-FU , 225 mg/m(2 ) per day , Monday to Friday , plus irinotecan , 50 mg/m(2 ) once weekly × 4 , plus pelvic radiation therapy ( RT ) , 45 Gy at 1.8 Gy per day and a boost of 5.4 Gy for T3 and 9 Gy for T4 cancers ( Arm 2 ) . Surgery was performed 4 to 10 weeks later . RESULTS All eligible patients ( n=103 ) are included in this analysis ; 2 ineligible patients were excluded , and 1 patient withdrew consent . Ninety-eight of 103 patients ( 95 % ) underwent resection . Four patients did not undergo surgery for either disease progression or patient refusal , and 1 patient died during induction chemotherapy . The median time of follow-up was 6.4 years in Arm 1 and 7.0 years in Arm 2 . The pathological complete response ( pCR ) rates were 30 % in Arm 1 and 26 % in Arm 2 . Locoregional recurrence rates were 16 % in Arm 1 and 17 % in Arm 2 . Five-year survival rates were 61 % and 75 % and Disease-specific survival rates were 78 % and 85 % for Arm1 and Arm 2 , respectively . Five second primaries occurred in patients on Arm 1 , and 1 second primary occurred in Arm 2 . CONCLUSIONS High rates of disease-specific survival were seen in each arm . Overall survival appears affected by the development of unrelated second cancers . The high pCR rates with 5-FU and higher dose radiation in T4 cancers provide opportunity for increased R0 resections and improved survival The Stockholm III Trial r and omized patients with primary operable rectal cancers to either short‐course radiotherapy ( RT ) with immediate surgery ( SRT ) , short‐course RT with surgery delayed 4–8 weeks ( SRT‐delay ) or long‐course RT with surgery delayed 4–8 weeks . This preplanned interim analysis examined the pathological outcome of delaying surgery BACKGROUND Organ preservation is a concept proposed for patients with rectal cancer after a good clinical response to neoadjuvant chemotherapy , to potentially avoid morbidity and side-effects of rectal excision . The objective of this study was to compare local excision and total mesorectal excision in patients with a good response after chemoradiotherapy for lower rectal cancer . METHODS We did a prospect i ve , r and omised , open-label , multicentre , phase 3 trial at 15 tertiary centres in France that were experts in the treatment of rectal cancer . Patients aged 18 years and older with stage T2T3 lower rectal carcinoma , of maximum size 4 cm , who had a good clinical response to neoadjuvant chemoradiotherapy ( residual tumour ≤2 cm ) were central ly r and omly assigned by the surgeon before surgery to either local excision or total mesorectal excision surgery . R and omisation , which was done via the internet , was not stratified and used permuted blocks of size eight . In the local excision group , a completion total mesorectal excision was required if tumour stage was ypT2 - 3 . The primary endpoint was a composite outcome of death , recurrence , morbidity , and side-effects at 2 years after surgery , to show superiority of local excision over total mesorectal excision in the modified intention-to-treat ( ITT ) population ( expected proportions of patients having at least one event were 25 % vs 60 % for superiority ) . This trial was registered with Clinical Trials.gov , number NCT00427375 . FINDINGS From March 1 , 2007 , to Sept 24 , 2012 , 186 patients received chemoradiotherapy and were enrolled in the study . 148 good clinical responders were r and omly assigned to treatment , three were excluded ( because they had metastatic disease , tumour > 8 cm from anal verge , and withdrew consent ) , and 145 were analysed : 74 in the local excision group and 71 in the total mesorectal excision group . In the local excision group , 26 patients had a completion total mesorectal excision . At 2 years in the modified ITT population , one or more events from the composite primary outcome occurred in 41 ( 56 % ) of 73 patients in the local excision group and 33 ( 48 % ) of 69 in the total mesorectal excision group ( odds ratio 1·33 , 95 % CI 0·62 - 2·86 ; p=0·43 ) . In the modified ITT analysis , there was no difference between the groups in all components of the composite outcome , and superiority was not shown for local excision over total mesorectal excision . INTERPRETATION We failed to show superiority of local excision over total mesorectal excision , because many patients in the local excision group received a completion total mesorectal excision that probably increased morbidity and side-effects , and compromised the potential advantages of local excision . Better patient selection to avoid unnecessary completion total mesorectal excision could improve the strategy . FUNDING National Cancer Institute of France , Sanofi , Roche Pharma Background There is increasing interest in nonoperative management ( NOM ) for rectal cancer with complete clinical response ( cCR ) after neoadjuvant chemoradiation ( nCRT ) . Objective The aim of this systematic review was to summarize the available data on NOM , with the intention of formulating st and ardized protocol s on which to base future investigations . Methods A systematic review following the Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines was conducted . A highly sensitive literature search identified all relevant studies published between January 2004 and December 2016 . Data extraction and quality assessment was performed independently by two authors , and resolved by consensus with a third review er . Results In total , 15 studies , including 920 patients , met the inclusion criteria ; 575 ( 62.5 % ) of these patients underwent NOM after cCR , with the remaining patients forming a surgical control group . The weighted mean follow-up was 39.4 ( 12.7 ) months in the NOM group and 39.8 ( 5.1 ) months in the surgery group . The pooled regrowth rate in the NOM group was 21.3 % at a mean of 15.6 ( 7.0 ) months . Surgical salvage was possible and was undertaken in 93.2 % of these patients . Overall survival in the NOM group was 91.7 % , while disease-free survival was 82.7 % . For the comparison proctectomy group , pooled rates of local recurrence , overall survival , and disease-free survival were 8.4 , 92.4 , and 87.5 % , respectively . Conclusion NOM may be a feasible option for surgically eligible rectal cancer patients with cCR after nCRT . Before such a strategy can be widely implemented , further prospect i ve data are required with st and ardized definitions , diagnostic criteria , and management protocol s , with an emphasis on shared patient – provider decision making and patient-centered outcomes BACKGROUND Further optimisation of present st and ard chemoradiation is needed in patients with locally advanced rectal cancer . Veliparib , an oral poly(ADP-ribose ) polymerase inhibitor , has been shown to enhance the antitumour activity of chemotherapy and radiotherapy in pre clinical models . We aim ed to establish the maximum tolerated dose and establish the recommended phase 2 dose of veliparib combined with neoadjuvant capecitabine and radiotherapy . METHODS This phase 1b , open-label , multicentre , dose-escalation study was done at six hospitals ( one in Australia and five in the USA ) . Patients were eligible if they were aged 18 years or more and were newly diagnosed with stage II to III locally advanced , resectable adenocarcinoma of the rectum with a distal tumour border of less than 12 cm from anal verge . Patients were ineligible if they had received anticancer therapy or surgery ( except colostomy or ileostomy ) 28 days or less before the first dose of study drug , previous pelvic radiotherapy , or previous treatment with poly ( ADP-ribose ) polymerase inhibitors . Enrolled patients received capecitabine ( 825 mg/m2 orally twice daily ) with radiotherapy ( 50·4 Gy in 1·8 Gy fractions daily , approximately 5 days consecutively per week for about 5·5 weeks ) . Veliparib ( 20 - 400 mg orally twice daily ) was administered daily starting on day 2 of week 1 and continuing until 2 days after radiotherapy completion . Patients underwent total mesorectal excision 5 - 10 weeks after radiotherapy completion . The primary objectives were to establish the maximum tolerated dose and recommended phase 2 dose of veliparib plus capecitabine and radiotherapy , with an exposure-adjusted continual re assessment methodology . Efficacy and safety analyses were done per protocol . The reported study has completed accrual and all analyses are final . This trial is registered with Clinical Trials.gov , number NCT01589419 . FINDINGS Between June 12 , 2012 , and Jan 13 , 2015 , 32 patients received veliparib ( 22 in the dose-escalation group ; ten in the safety expansion group ) ; 31 were assessable for efficacy ( < 400 mg , n=16 ; 400 mg , n=15 ) . During dose escalation , grade 2 dose-limiting toxic effects occurred in two patients ; no grade 3 - 4 dose-limiting toxic effects were noted . Therefore , the maximum tolerated dose was not reached ; the recommended phase 2 dose was selected as 400 mg twice daily . The most common treatment-emergent adverse events in all 32 patients were nausea ( 17 [ 53 % ] ) , diarrhoea ( 16 [ 50 % ] ) , and fatigue ( 16 [ 50 % ] ) . Grade 3 diarrhoea was noted in three ( 9 % ) of 32 patients ; no grade 4 events were reported . Veliparib pharmacokinetics were dose proportional , with no effect on capecitabine pharmacokinetics . Tumour downstaging after surgery was noted in 22 ( 71 % ) of 31 patients ; nine ( 29 % ) of 31 patients achieved a pathological complete response . INTERPRETATION Veliparib plus capecitabine and radiotherapy had an acceptable safety profile and showed a dose-proportional pharmacokinetic profile with no effect on the pharmacokinetics of capecitabine . Preliminary antitumour activity warrants further evaluation . FUNDING AbbVie We sought to evaluate the efficacy and safety data of a combination regimen using weekly irinotecan in combination with capecitabine and concurrent radiotherapy ( CapIri-RT ) as neoadjuvant treatment in rectal cancer in a phase-II trial . Patients with rectal cancer clinical stages T3/4 Nx or N+ were recruited to receive irinotecan ( 50 mg m−2 weekly ) and capecitabine ( 500 mg m−2 bid days 1–38 ) with a concurrent RT dose of 50.4 Gy . Surgery was scheduled 4–6 weeks after the completion of chemoradiation . A total of 36 patients ( median age 62 years ; m/f : 27:9 ) including three patients with local recurrence were enclosed onto the trial . The median distance of the tumour from the anal verge was 5 cm . The main toxicity observed was ( NCI-CTC grade s 1/2/3/4 ( n ) ) : Anaemia 23/9/−/− ; leucocytopenia 12/7/7/2 , diarrhoea 13/15/4/− , nausea/vomiting 9/10/2/− , and increased activity of transaminases 3/3/1/−. One patient had a reversible episode of ventricular fibrillation during chemoradiation , most probably caused by capecitabine . The relative dose intensity was ( median/mean ( % ) ) : irinotecan 95/91 , capecitabine 100/92 ) . Thirty-four patients underwent surgery ( anterior resection n=25 ; abdomino-perineal resection n=6 ; Hartmann 's procedure n=3 ) . R0-resection was accomplished in all patients . Two patients died in the postoperative course from septic complications . Pathological complete remission was observed in five out of 34 resected patients ( 15 % ) , and nine patients showed microfoci of residual tumour ( 26 % ) . After a median follow-up of 28 months one patient had developed a local recurrence , and five patients distant metastases . Three-year overall survival for all patients with surgery ( excluding three patients treated for local relapse or with primary metastatic disease ) was 80 % . In summary , preoperative chemoradiation with CapIri-RT exhibits promising efficacy whereas showing managable toxicity . The local recurrence and distant failure rates observed after a median 28 months are low compared with st and ard 5-fluorouracil based therapy PURPOSE CPT-11 sensitizes tumor cells to radiation and in combination therapy with 5-fluorouracil ( 5-FU ) results in enhanced cytotoxicity to metastatic colorectal cancer . We report the results from a Phase II trial of preoperative radiotherapy ( RT ) , CPT-11 , and 5-FU for patients with ultrasound-staged T3 rectal cancer . METHODS AND MATERIAL S Between April 1999 and August 2001 , 32 patients ( 21 men , 11 women ; median age 52 years , range 40 - 74 ) with biopsy-proven adenocarcinoma of the rectum were enrolled in the study . All patients underwent endorectal ultrasonography for staging ( uT3N0 = 19 ; uT3N1 = 13 ; uT2N1 = 1 ) . RT was prescribed to the draining lymph nodes ( 45 Gy in 1.8-Gy daily fractions ) and tumor ( 50.4 Gy in 1.8-Gy daily fractions ) . Patients also received concurrent CPT-11 ( 50 mg/m(2 ) , Days 1 , 8 , 15 , and 22 ) and 5-FU ( 200 mg/m(2 ) daily , 7 d/wk , Days 1 - 33 ) . Surgical resection was performed 6 - 10 weeks after completing chemoradiotherapy . RESULTS Acute toxicity was frequently observed , and 18 patients ( 56 % ) required either a chemotherapy dose reduction or RT interruption of > 3 days . One patient withdrew because of diarrhea and abdominal cramping ( Grade III ) after 10 days of treatment . Although no Grade IV toxicity was observed , Grade III diarrhea ( n = 9 , 28 % ) , mucositis ( n = 7 , 21 % ) , rectal sores ( n = 7 , 21 % ) , abdominal cramping ( n = 3 , 9 % ) were noted . Of the 32 patients who underwent surgery , 12 had a complete pathologic response . Of the 32 patients , the disease of 23 ( 71 % ) was downstaged . The average length of hospitalization was between 5 and 12 days , with 1 patient staying 33 days . All patients were followed for disease-free survival . CONCLUSION Although associated with frequent acute toxicity , the regimen is associated with significant tumor " downstaging . " Additional patients and longer follow-up are necessary to define the role of this regimen fully Purpose : Nelfinavir , a PI3 K pathway inhibitor , is a radiosensitizer that increases tumor blood flow in pre clinical models . We conducted an early-phase study to demonstrate the safety of nelfinavir combined with hypofractionated radiotherapy ( RT ) and to develop biomarkers of tumor perfusion and radiosensitization for this combinatorial approach . Experimental Design : Ten patients with T3 - 4 N0 - 2 M1 rectal cancer received 7 days of oral nelfinavir ( 1,250 mg b.i.d . ) and a further 7 days of nelfinavir during pelvic RT ( 25 Gy/5 fractions/7 days ) . Perfusion CT ( p-CT ) and DCE-MRI scans were performed pretreatment , after 7 days of nelfinavir and prior to the last fraction of RT . Biopsies taken pretreatment and 7 days after the last fraction of RT were analyzed for tumor cell density ( TCD ) . Results : There were 3 drug-related grade 3 adverse events : diarrhea , rash , and lymphopenia . On DCE-MRI , there was a mean 42 % increase in median Ktrans , and a corresponding median 30 % increase in mean blood flow on p-CT during RT in combination with nelfinavir . Median TCD decreased from 24.3 % at baseline to 9.2 % in biopsies taken 7 days after RT ( P = 0.01 ) . Overall , 5 of 9 evaluable patients exhibited good tumor regression on MRI assessed by tumor regression grade ( mrTRG ) . Conclusions : This is the first study to evaluate nelfinavir in combination with RT without concurrent chemotherapy . It has shown that nelfinavir-RT is well tolerated and is associated with increased blood flow to rectal tumors . The efficacy of nelfinavir-RT versus RT alone merits clinical evaluation , including measurement of tumor blood flow . Clin Cancer Res ; 22(8 ) ; 1922–31 . © 2016 AACR . See related commentary by Meyn et al. , p. Background Perioperatory chemoradiotherapy ( CRT ) improves local control and survival in patients with locally advanced rectal cancer ( LARC ) . The objective of the current study was to evaluate the addition of bevacizumab ( BEV ) to preoperative capecitabine (CAP)-based CRT in LARC , and to explore biomarkers for downstaging . Methods Patients ( pts ) were r and omized to receive 5 weeks of radiotherapy 45 Gy/25 fractions with concurrent CAP 825 mg/m2 twice daily 5 days per week and BEV 5 mg/kg once every 2 weeks ( 3 doses ) ( arm A ) , or the same schedule without BEV ( arm B ) . The primary end point was pathologic complete response ( ypCR : ypT0N0 ) . Results Ninety pts were included in arm A ( 44 ) or arm B ( 46 ) . Grade 3–4 treatment-related toxicity rates were 16 % and 13 % , respectively . All patients but one ( arm A ) proceeded to surgery . The ypCR rate was 16 % in arm A and 11 % in arm B ( p = 0.54 ) . Fifty-nine percent vs 39 % of pts achieved T-downstaging ( arm A vs arm B ; p = 0.04 ) . Serial sample s for biomarker analyses were obtained for 50 out of 90 r and omized pts ( arm A/B : 22/28 ) . Plasma angiopoietin-2 ( Ang-2 ) levels decreased in arm A and increased in arm B ( p < 0.05 at all time points ) . Decrease in Ang-2 levels from baseline to day 57 was significantly associated with tumor downstaging ( p = 0.02 ) . Conclusions The addition of BEV to CAP-based preoperative CRT has shown to be feasible in LARC . The association between decreasing Ang-2 levels and tumor downstaging should be further vali date d in customized studies .Trial registry Clinical trials.gov identifier NCT01043484 . Trial registration date : 12/30/2009 PURPOSE Preoperative chemoradiotherapy followed by surgery represents the st and ard of care for locally advanced rectal cancer ( LARC ) . Cetuximab has proved activity in advanced colorectal cancer , and its incorporation in preoperative treatment may increase tumor downstaging . METHODS AND MATERIAL S After biopsy and staging , uT3/uT4 N0/+ LARC received single-agent cetuximab in three doses , followed by weekly cetuximab plus 5-fluorouracil ( 5-FU ) , concomitantly with RT . Sample size was calculated according to Bryant and Day test , a two-stage design with at least 10 pathologic complete remissions observed in 60 patients ( pts ) able to complete the treatment plan . RESULTS Forty pts with LARC were entered : male/female = 34/6 ; median age : 61 ( range , 28 - 77 ) ; 12 uT3N0 Ed(30 % ) ; 25 uT3N1 ( 62 % ) ; 3 uT4N1 ( 8 % ) ; all Eastern Cooperative Oncology Group = 0 . Thirty-five pts completed neoadjuvant treatment ; 5 ( 12 % ) withdrew therapy after one cetuximab administration : three for hypersensitivity reactions , one for rapid progression , and one for purulent arthritis . They continued 5-FU in continuous infusion in association with RT . Thirty-one pts ( 77 % ) presented with acnelike rash ; dose reduction/interruption of treatment was necessary in six pts ( 15 % ) : two for Grade 3 acnelike rash , two for Grade 3 gastrointestinal toxicity , and two for refusal . Thirty-eight pts were evaluable for pathological response ( one patient refused surgery , and one was progressed during neoadjuvant treatment ) . Pathological staging was : pT0N0 three pts ( 8 % ) , pT1N0 1 pt ( 3 % ) ; pT2N0 13 pts ( 34 % ) , and pT3 19 pts ( 50 % ) ( N0:9 , N1:5 ; N2:5 ) ; pT4 2 pts ( 5 % ) . CONCLUSIONS Preoperative treatment with 5-FU , cetuximab , and pelvic RT is feasible with acceptable toxicities ; however , the rate of pathologic responses is disappointingly low PURPOSE To assess long-term clinical outcomes of preoperative chemoradiotherapy of magnetic resonance imaging (MRI)-defined locally advanced rectal adenocarcinoma using concurrent irinotecan and capecitabine . PATIENTS AND METHODS One hundred ten patients without distant metastases entered this phase II trial North West/North Wales Clinical Oncology Group ( NWCOG ) -2 after MRI demonstration of tumor threatening ( ≤ 2 mm ) or involving mesorectal fascia . Pelvic radiotherapy was given to 45 Gy in 25 fractions over 5 weeks with concurrent oral capecitabine at 650 mg/m(2 ) twice per day continuously days 1 through 35 and intravenous irinotecan at 60 mg/m(2 ) once weekly weeks 1 to 4 . One hundred seven patients subsequently underwent surgical resection . RESULTS Comparing prechemoradiotherapy MRI scans with histology of the resected specimen , 72 patients ( 67 % ) had their initial MRI T stage downstaged and 64 patients ( 80 % ) had their N stage downstaged . Twenty-four patients ( 22 % ) demonstrated a pathologic complete response ( ypCR ) and 98 patients ( 92 % ) demonstrated a negative circumferential resection margin ( > 1 mm ) . Three-year local recurrence-free survival was 96.9 % , metastasis-free survival ( MFS ) was 71.1 % , disease-free survival was ( DFS ) 63.5 % , and overall survival ( OS ) was 88.2 % . By univariate analysis , lower histologic stage was significantly associated with superior MFS , DFS , and OS , whether expressed as ypT0 - 2 versus ypT3 - 4 , ypN0 versus ypN1 - 2 , or ypCR/microfoci ( near-ypCR ) versus other patients . By multivariate analysis both ypN stage ( P = .048 ) and ypCR/microfoci/others ( P = .013 ) remained significant predictors of DFS but only ypCR/microfoci/others for OS ( P = .005 ) with no difference in outcome between ypCR compared to microfoci . CONCLUSION This regimen demonstrates high response rates and promising long-term survival . Downstaging to ypCR/microfoci may be a useful short-term surrogate for long-term survival but needs validation in large phase III trials powered for survival outcomes PURPOSE To evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer . PATIENTS AND METHODS Patients with operable magnetic resonance imaging-defined high-risk rectal cancer received four cycles of capecitabine/oxaliplatin ( CAPOX ) followed by capecitabine chemoradiotherapy , surgery , and adjuvant CAPOX ( four cycles ) or the same regimen plus weekly cetuximab ( CAPOX+C ) . The primary end point was complete response ( CR ; pathologic CR or , in patients not undergoing surgery , radiologic CR ) in patients with KRAS/BRAF wild-type tumors . Secondary end points were radiologic response ( RR ) , progression-free survival ( PFS ) , overall survival ( OS ) , and safety in the wild-type and overall population s and a molecular biomarker analysis . RESULTS One hundred sixty-five eligible patients were r and omly assigned . Ninety ( 60 % ) of 149 assessable tumors were KRAS or BRAF wild type ( CAPOX , n = 44 ; CAPOX+C , n = 46 ) , and in these patients , the addition of cetuximab did not improve the primary end point of CR ( 9 % v 11 % , respectively ; P = 1.0 ; odds ratio , 1.22 ) or PFS ( hazard ratio [ HR ] , 0.65 ; P = .363 ) . Cetuximab significantly improved RR ( CAPOX v CAPOX+C : after chemotherapy , 51 % v 71 % , respectively ; P = .038 ; after chemoradiation , 75 % v 93 % , respectively ; P = .028 ) and OS ( HR , 0.27 ; P = .034 ) . Skin toxicity and diarrhea were more frequent in the CAPOX+C arm . CONCLUSION Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer , but the primary end point of improved CR was not met PURPOSE The aim of this study was to determine the efficacy of capecitabine ( Xeloda ) , an oral fluoropyrimidine , as a radiosensitizer in the neoadjuvant treatment of locally advanced rectal cancer ( LARC ) . METHODS AND MATERIAL S We conducted a phase II study of capecitabine ( 825 mg/m2 orally , twice daily continuous ) with radiotherapy ( 52.5 Gy/30 fractions to the primary tumor and perirectal nodes ) in 54 patients with LARC ( node-negative > or = T3 or any node-positive tumor ) staged by endoscopic ultrasound ( EUS ) . The primary endpoint was pathologic response rate ; secondary endpoints included toxicity profiles and survival parameters . RESULTS Of the 54 patients ( median age , 56.7 years ; range , 21.3 - 78.7 years ; male : female ratio , 1.7 ; Eastern Cooperative Oncology Group performance status 0 - 1 : 100 % ) , 51 patients ( 94 % ) had T3N0 or T3N1 disease by EUS . Surgery was not performed in 3 patients ; 2 of these patients had metastatic disease , and the third patient refused after a complete clinical response . Of the 51 patients evaluable for pathologic response , 9 patients ( 18 % ) achieved complete response , and 12 patients ( 24 % ) had microscopic residual disease ( < 10 % viable cells ) . In addition , 26 patients of all 54 patients ( 51 % ) achieved T-downstaging , and 15 patients of 29 patients ( 52 % ) achieved N-downstaging . Grade 3/4 toxicities were radiation dermatitis ( 9 % ) and diarrhea ( 2 % ) . Sphincter preservation rate for tumor < or = 5 cm from the anal verge was 67 % ( 18/27 ) . CONCLUSION This regimen of radiotherapy plus capecitabine is well tolerated and is more convenient than protracted venous infusion of 5-FU . The pathologic response rate is comparable to our previous experience using protracted venous infusion 5-FU for LARC BACKGROUND The aim of this phase II study was to assess the activity of panitumumab in combination with oxaliplatin , 5-fluorouracil , and external radiotherapy ( RT ) as preoperative treatment in locally advanced rectal cancer patients . PATIENTS AND METHODS Patients had rectal adenocarcinoma , cT3N+ or cT4N-/+ stage , located < 12 cm from the anal margin . Panitumumab was administered before the start of chemo-RT , and every 2 weeks in combination with 5-fluorouracil-oxaliplatin with concurrent RT . Rectal surgery was carried out 7 - 8 weeks after the end of neoadjuvant treatment . The primary end point was a pathological complete response rate of 25 % . RESULTS Sixty patients were enrolled from February 2007 to October 2009 . Fifty-five ( 91.7 % ) patients underwent surgery . Rate of pathological complete response was 21.1 % ( 95 % confidence interval 10.4 % to 31.6 % ) . Pathological downstaging occurred in 33 of 57 ( 57.9 % ) patients . Grade 3 - 4 toxicity during neoadjuvant treatment was diarrhea ( 38.9 % ) , cutaneous reactions ( 18.6 % ) , nausea ( 5.1 % ) , asthenia ( 3.4 % ) , anorexia ( 3.4 % ) , and neutropenia ( 1.7 % ) . One toxic death was observed for diarrhea . CONCLUSIONS In our study , the primary end point is not reached and panitumumab combination treatment was associated with high incidence of grade 3 - 4 diarrhea . The higher pathological complete response rate in comparison with the results of previous neoadjuvant rectal cancer trials with anti-epidermal growth factor receptor monoclonal antibodies supports further studies necessary to underst and the possibility of optimal regimens and sequences with chemo-RT Our goal was to optimize the radiosensitizing potential of anti-epidermal growth factor receptor ( EGFR ) monoclonal antibodies , when given concomitantly with preoperative radiotherapy in KRAS wild-type locally advanced rectal cancer ( LARC ) . Based on pre- clinical studies conducted by our group , we design ed a phase II trial in which panitumumab ( 6 mg/kg/q2 weeks ) was combined with preoperative radiotherapy ( 45 Gy in 25 fractions ) to treat cT3 - 4/N + KRAS wild-type LARC . The primary endpoint was complete pathologic response ( pCR ) ( H0 = 5 % , H1 = 17 % , α = 0.05 , β = 0.2 ) . From 19 enrolled patients , 17 ( 89 % ) were evaluable for pathology assessment . Although no pCR was observed , seven patients ( 41 % ) had grade 3 Dworak pathological tumor regression . The regimen was safe and was associated with 95 % of sphincter-preservation rate . No NRAS , BRAF , or PI3KCA mutation was found in this study , but one patient ( 5 % ) showed loss of PTEN expression . The quantification of plasma EGFR lig and s during treatment showed significant upregulation of plasma TGF-α and EGF following panitumumab administration ( p < 0.05 ) . At surgery , patients with important pathological regression ( grade 3 Dworak ) had higher plasma TGF-α ( p = 0.03 ) but lower plasma EGF ( p = 0.003 ) compared to those with grade 0–2 Dworak . Our study suggests that concomitant panitumumab and preoperative radiotherapy in KRAS wild-type LARC is feasible and results in some tumor regression . However , pCR rate remained modest . Given that the primary endpoint of our study was not reached , we remain unable to recommend the use of panitumumab as a radiosensitizer in KRAS wild-type LARC outside a research setting PURPOSE Preoperative chemoradiotherapy ( CRT ) for locally advanced rectal cancer has shown benefit over postoperative CRT ; however , a st and ard CRT regimen has yet to be defined . We performed a prospect i ve concurrent CRT Phase II study with irinotecan and capecitabine in patients with locally advanced rectal cancer to investigate the efficacy and safety of this regimen . METHODS AND MATERIAL S Patients with locally advanced , nonmetastatic , and mid-to-lower rectal cancer were enrolled . Radiotherapy was delivered in 1.8-Gy daily fractions for a total of 45 Gy in 25 fractions , followed by a coned-down boost of 5.4 Gy in 3 fractions . Concurrent chemotherapy consisted of 40 mg/m(2 ) of irinotecan per week for 5 consecutive weeks and 1,650 mg/m(2 ) of capecitabine per day for 5 days per week ( weekdays only ) from the first day of radiotherapy . Total mesorectal excision was performed within 6 ± 2 weeks . The pathologic responses and survival outcomes were included for the study endpoints . RESULTS In total , 48 patients were enrolled ; 33 ( 68.7 % ) were men and 15 ( 31.3 % ) were women , and the median age was 59 years ( range , 32 - 72 years ) . The pathologic complete response rate was 25.0 % ( 11 of 44 ; 95 % confidence interval , 12.2 - 37.8 ) and 8 patients ( 18.2 % [ 8 of 44 ] ) showed near-total tumor regression . The 5-year disease-free and overall survival rates were 75.0 % and 93.6 % , respectively . Grade 3 toxicities included leukopenia ( 3 [ 6.3 % ] ) , neutropenia ( 1 [ 2.1 % ] ) , infection ( 1 [ 2.1 % ] ) , alanine aminotransferase elevation ( 1 [ 2.1 % ] ) , and diarrhea ( 1 [ 2.1 % ] ) . There was no Grade 4 toxicity or treatment-related death . CONCLUSIONS Preoperative CRT with irinotecan and capecitabine with treatment-free weekends showed very mild toxicity profiles and promising results in terms of survival Background : The influence of EGFR pathway mutations on cetuximab-containing rectal cancer preoperative chemoradiation ( CRT ) is uncertain . Methods : In a prospect i ve phase II trial ( EXCITE ) , patients with magnetic resonance imaging (MRI)-defined non-metastatic rectal adenocarinoma threatening/involving the surgical resection plane received pelvic radiotherapy with concurrent capecitabine , irinotecan and cetuximab . Resection was recommended 8 weeks later . The primary endpoint was histopathologically clear ( R0 ) resection margin . Pre-planned retrospective DNA pyrosequencing ( PS ) and next generation sequencing ( NGS ) of KRAS , NRAS , PIK3CA and BRAF was performed on the pre-treatment biopsy and resected specimen . Results : Eighty-two patients were recruited and 76 underwent surgery , with R0 resection in 67 ( 82 % , 90%CI : 73–88 % ) ( four patients with clinical complete response declined surgery ) . Twenty – four patients ( 30 % ) had an excellent clinical or pathological response ( ECPR ) . Using NGS 24 ( 46 % ) of 52 matched biopsies/resections were discrepant : ten patients ( 19 % ) gained 13 new resection mutations compared to biopsy ( 12 KRAS , one PIK3CA ) and 18 ( 35 % ) lost 22 mutations ( 15 KRAS , 7 PIK3CA ) . Tumours only ever testing RAS wild-type had significantly greater ECPR than tumours with either biopsy or resection RAS mutations ( 14/29 [ 48 % ] vs 10/51 [ 20 % ] , P=0.008 ) , with a trend towards increased overall survival ( HR 0.23 , 95 % CI 0.05–1.03 , P=0.055 ) . Conclusions : This regimen was feasible and the primary study endpoint was met . For the first time using pre-operative rectal CRT , emergence of clinical ly important new resection mutations is described , likely reflecting intratumoural heterogeneity manifesting either as treatment-driven selective clonal expansion or a geographical biopsy sampling miss Purpose : Capecitabine ( Xeloda ) is a novel fluoropyrimidine carbamate rationally design ed to generate 5-fluorouracil ( 5-FU ) preferentially in tumors . The purpose of this study was to demonstrate the preferential activation of capecitabine , after oral administration , in tumor in colorectal cancer patients , by the comparison of 5-FU concentrations in tumor tissues , healthy tissues and plasma . Methods : Nineteen patients requiring surgical resection of primary tumor and /or liver metastases received 1,255 mg/m2 of capecitabine twice daily p.o . for 5–7 days prior to surgery . On the day of surgery , sample s of tumor tissue , adjacent healthy tissue and blood sample s were collected simultaneously from each patient , 2 to 12 h after the last dose of capecitabine had been administered . Concentrations of 5-FU in various tissues and plasma were determined by HPLC . The activities of the enzymes ( CD , TP and DPD ) involved in the formation and catabolism of 5-FU were measured in tissue homogenates , by catabolic assays . Results : The ratio of 5-FU concentrations in tumor to adjacent healthy tissue ( T/H ) was used as the primary marker for the preferential activation of capecitabine in tumor . In primary colorectal tumors , the concentration of 5-FU was on average 3.2 times higher than in adjacent healthy tissue ( P=0.002 ) . The mean liver metastasis/healthy tissue 5-FU concentration ratio was 1.4 ( P=0.49 , not statistically different ) . The mean tissue/plasma 5-FU concentration ratios exceeded 20 for colorectal tumor and ranged from 8 to 10 for other tissues . Conclusions : The results demonstrated the preferential activation of capecitabine to 5-FU in colorectal tumor , after oral administration to patients . This is explained to a great extent by the activity of TP in colorectal tumor tissue , ( the enzyme responsible for the conversion of 5′-DFUR to 5-FU ) , which is approximately four times that in adjacent healthy tissue . In the liver , TP activity is approximately equal in metastatic and healthy tissue , which explains the lack of preferential activation of capecitabine in these tissues BACKGROUND To assess the safety and preliminary efficacy of concurrent radiotherapy , capecitabine , and cetuximab in the preoperative treatment of patients with rectal cancer . PATIENTS AND METHODS Forty patients with rectal cancer ( T3-T4 , and /or N+ , endorectal ultrasound ) received preoperative radiotherapy ( 1.8 Gy , 5 days/week for 5 weeks , total dose 45 Gy , three-dimensional conformal technique ) in combination with cetuximab [ initial dose 400 mg/m(2 ) intravenous given 1 week before the beginning of radiation followed by 250 mg/m(2)/week for 5 weeks ] and capecitabine for the duration of radiotherapy ( 650 mg/m(2 ) orally twice daily , first dose level ; 825 mg/m(2 ) twice daily , second dose level ) . RESULTS Four and six patients were treated at the first and second dose level of capecitabine , respectively . No dose-limiting toxicity occurred . Thirty additional patients were treated with capecitabine at 825 mg/m(2 ) twice daily . The most frequent grade 1/2 side-effects were acneiform rash ( 87 % ) , diarrhea ( 65 % ) , and fatigue ( 57 % ) . Grade 3 diarrhea was found in 15 % . Three grade 4 toxic effects were recorded : one myocardial infa rct ion , one pulmonary embolism , and one pulmonary infection with sepsis . Two patients ( 5 % ) had a pathological complete response . CONCLUSIONS Preoperative radiotherapy in combination with capecitabine and cetuximab is feasible with some patients achieving pathological downstaging The objective of this study was to evaluate the maximum tolerated dose ( MTD ) and recommended dose of irinotecan administered as a 5-day schedule synchronously with 5-fluorouracil ( 5FU ) , leucovorin ( LV ) and preoperative pelvic radiation ( 45 Gy ) for primary borderline/unresectable , locally advanced rectal cancer . The study used escalating doses of intravenous irinotecan ( 6 , 8 , 10 , 12 , 14 , 16 , 18 , and 20 mg m−2 ) administered on days 1–5 and 29–33 followed by low dose LV ( 20 mg m−2 ) and 5FU ( 350 mg m−2 over 1 h ) in sequential cohorts . Preoperative pelvic radiotherapy using a three- or four-field technique and megavoltage photons comprised 45 Gy given in 25 fractions , 1.8 Gy per fraction . Surgery in the form of mesorectal excision was performed 6–10 weeks later . Histopathological examination of the resected specimen was performed according to techniques of Quirke , and compared with clinical staging . A distance of 1 mm or less between the peripheral extent of the tumour and the radial resection margin defined an involved circumferential resection margin ( CRM ) . The MTD was determined as the dose causing more than a third of patients to have a dose-limiting toxicity ( DLT ) defined as specific grade 3 or 4 toxicities . Once the MTD was reached , a further 14 patients were treated at the dose level below the MTD . In total , 57 patients received irinotecan at the eight dose levels . The final cohort reached DLT after only four patients had been enrolled . The median age was 62 years ( range 26–75 ) , 37 male and 20 female subjects . The MTD of irinotecan in this schedule was 20 mg m−2 when three out of four patients experienced DLT . Dose limiting grade 3 or 4 diarrhoea was reported in seven out of 57 patients , three at the 20 mg m−2 dose level . Serious haematological toxicity ( grade 3 ) was minimal and reported in only three patients ; one grade 3 neutropaenia , one grade 4 neutropaenia and one grade 3 febrile neutropaenia and anaemia . Compliance was good with 93 and 89 % of patients completing radiotherapy and chemotherapy , respectively . The remaining patients had only minor deviations from protocol therapy . Eight patients did not proceed to surgery , in six cases because they remained unresectable or had developed metastatic disease , one patient was unfit for surgery and one died as a result of complications from radiotherapy . Forty-nine patients underwent a potentially curative surgical resection . Histopathological examination of the resected specimen demonstrated pCR 12 out of 49 ( 24 % ) and 12 out of 57 ( 21 % ) overall . A histologically confirmed clear circumferential resection margin ( CRM ) was achieved in 39 out of 49 ( 80 % ) of those resected , and 39 out of 57 ( 68 % ) overall . In conclusion , MTD with this scheduled regimen of irinotecan is 20 mg m−2 ( days 1–5 and 29–33 ) . The acceptable toxicity and compliance at 18 mg m−2 recommend testing this dose in future phase III studies . The tumour downstaging and complete resection rates ( negative CRM ) are encouragingly high for this very locally advanced group BACKGROUND Patients with metastatic colorectal cancer that harbors KRAS mutations in exon 2 do not benefit from anti-epidermal growth factor receptor ( EGFR ) therapy . Other activating RAS mutations may also be negative predictive biomarkers for anti-EGFR therapy . METHODS In this prospect ive-retrospective analysis , we assessed the efficacy and safety of panitumumab plus oxaliplatin , fluorouracil , and leucovorin ( FOLFOX4 ) as compared with FOLFOX4 alone , according to RAS ( KRAS or NRAS ) or BRAF mutation status . A total of 639 patients who had metastatic colorectal cancer without KRAS mutations in exon 2 had results for at least one of the following : KRAS exon 3 or 4 ; NRAS exon 2 , 3 , or 4 ; or BRAF exon 15 . The overall rate of ascertainment of RAS status was 90 % . RESULTS Among 512 patients without RAS mutations , progression-free survival was 10.1 months with panitumumab-FOLFOX4 versus 7.9 months with FOLFOX4 alone ( hazard ratio for progression or death with combination therapy , 0.72 ; 95 % confidence interval [ CI ] , 0.58 to 0.90 ; P=0.004 ) . Overall survival was 26.0 months in the panitumumab-FOLFOX4 group versus 20.2 months in the FOLFOX4-alone group ( hazard ratio for death , 0.78 ; 95 % CI , 0.62 to 0.99 ; P=0.04 ) . A total of 108 patients ( 17 % ) with nonmutated KRAS exon 2 had other RAS mutations . These mutations were associated with inferior progression-free survival and overall survival with panitumumab-FOLFOX4 treatment , which was consistent with the findings in patients with KRAS mutations in exon 2 . BRAF mutations were a negative prognostic factor . No new safety signals were identified . CONCLUSIONS Additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4 . In patients who had metastatic colorectal cancer without RAS mutations , improvements in overall survival were observed with panitumumab-FOLFOX4 therapy . ( Funded by Amgen and others ; PRIME Clinical Trials.gov number , NCT00364013 . ) Although the development of multi-disciplinary management has improved the survival of colorectal cancer ( CRC ) , the prognosis of metastatic CRC patients remains poor . Accumulating evidence has demonstrated that immunotherapy with cancer vaccines and adoptive T cell transfusions may improve outcomes as an adjuvant to current st and ard CRC treatment . In this phase I/II study , 71 CRC patients who underwent radical surgery ( stage I – III , n = 46 ) or palliative surgery ( stage IV with non-resectable synchronous metastases , n = 25 ) were included . In the first part of this study , sentinel lymph nodes ( SLNs ) were intraoperatively identified in 55 patients ( 46 with stage I – III CRC and 9 with stage IV CRC ) . SLN-T lymphocytes were exp and ed ex vivo for a median of 28.5 days ( range 23–33 days ) . Thereafter , a median of 153 × 106 cells ( range 20.7–639.0 × 106 ) were transfused . No treatment-related toxicity was observed . In the second part of this study , the stage IV patients were routinely followed . The 24-month survival rate of the SLN-T lymphocyte group was significantly higher than that of the control group : 55.6 versus 17.5 % ( p = 0.02 ) . The median overall survival of the SLN-T lymphocyte and control groups was 28 and 14 months , respectively . Our study showed that adjuvant SLN-T lymphocyte immunotherapy is feasible and safe for postoperative CRC patients . Additionally , this therapy may improve the long-term survival of metastatic CRC . Further investigation of the clinical efficacy and anti-tumor immunity is warranted BACKGROUND We conducted a r and omized , phase II , multicenter study to evaluate the anti-epidermal growth factor receptor ( EGFR ) mAb panitumumab ( P ) in combination with chemoradiotherapy ( CRT ) with st and ard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer ( LARC ) . PATIENTS AND METHODS Patients with wild-type KRAS , T3 - 4 and /or N+ LARC were r and omly assigned to receive CRT with or without P ( 6 mg/kg ) . The primary end-point was pathological near-complete or complete tumor response ( pNC/CR ) , defined as grade 3 ( pNCR ) or 4 ( pCR ) histological regression by Dworak classification ( DC ) . RESULTS Forty of 68 patients were r and omly assigned to P + CRT and 28 to CRT . pNC/CR was achieved in 21 patients ( 53 % ) treated with P + CRT [ 95 % confidence interval ( CI ) 36%-69 % ] versus 9 patients ( 32 % ) treated with CRT alone ( 95 % CI : 16%-52 % ) . pCR was achieved in 4 ( 10 % ) and 5 ( 18 % ) patients , and pNCR in 17 ( 43 % ) and 4 ( 14 % ) patients . In immunohistochemical analysis , most DC 3 cells were not apoptotic . The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea ( 10%/6 % ) and anastomotic leakage ( 15%/4 % ) . CONCLUSIONS The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC result ed in a high pNC/CR rate , mostly grade 3 DC . The results of both treatment arms exceeded prespecified thresholds . The addition of panitumumab increased toxicity PURPOSE To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy ( NCRT ) with concurrent S-1 and irinotecan ( S-1/irinotecan ) therapy . METHODS AND MATERIAL S The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer . Patients received pelvic radiation therapy ( 45 Gy ) plus concurrent oral S-1/irinotecan . The median follow-up was 60 months . RESULTS Grade 3 adverse effects occurred in 7 patients ( 6 % ) , and the completion rate of NCRT was 87 % . All 115 patients ( 100 % ) were able to undergo R0 surgical resection . Twenty-eight patients ( 24 % ) had a pathological complete response ( ypCR ) . At 60 months , the local recurrence-free survival was 93 % , disease-free survival ( DFS ) was 79 % , and overall survival ( OS ) was 80 % . On multivariate analysis with a proportional hazards model , ypN2 was the only independent prognostic factor for DFS ( P=.0019 ) and OS ( P=.0064 ) in the study group as a whole . Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease , who had a DFS rate of 85.3 % . Both ypT ( P=.0065 ) and tumor location ( P=.003 ) were independent predictors of DFS . A combination of these factors was very strongly related to high risk of recurrence ( P<.0001 ) , which occurred most commonly in the lung . CONCLUSIONS NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival , with acceptable adverse effects in patients with rectal cancer . ypN2 is a strong predictor of dismal outcomes , and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease PURPOSE The st and ard of care in locally advanced rectal cancer is preoperative treatment with fluoropyrimidine-based chemoradiotherapy . Sorafenib works synergistically with radiation and inhibits Ras/Raf , PDFGR , and VEGFR . This phase I study evaluated the safety and efficacy of sorafenib with infusional 5-fluorouracil ( 5-FU ) and radiation in patients with locally advanced rectal cancer . METHODS AND MATERIAL S Patients with confirmed stage II or III rectal cancer were recruited in 4 cohorts of 3 patients per dose level , with an expansion cohort at the maximum tolerated dose . A 3 + 3 dose escalation design was used . Radiation was given in 28 fractions at 1.8 Gy ( 50.4 Gy ) day 1 - 5 at all dose levels . Initial dose of sorafenib was 200 mg qd and titrated up to 400 mg BID to determine the MTD . St and ard dose of infusional 5-FU was used ( 225 mg/m(2)/24h ) . Patients underwent surgery 6 - 10 weeks after neoadjuvant therapy . RESULTS Between August 2011 and August 2014 , 17 patients ( median age of 54 years ) were enrolled . After toxicities requiring dose interruptions were observed in cohort 1 ( 2 patients with grade 2 ( G2 ) and grade 3 ( G3 ) h and foot skin reaction and 1 patient with G2 mucositis ) , the protocol was amended , changing administration of chemotherapy and sorafenib from daily to days 1 - 5 only . With the amended protocol , the primary G3 toxicity was hypertension in 2 patients at the 200-mg adjusted dose level ( day1 - 5 ) and 1 patient at the 400-mg twice daily dose level . One patient had G3 ALT elevation at 400 mg , and no grade IV toxicities were observed . G1 and G2 toxicities included h and -foot skin reaction , diarrhea , mucositis , nausea , fatigue , and proctitis . No perioperative complications were seen . Two patients refused to undergo surgery . The pathological complete remission ( pCR ) rate was 33 % , and downstaging was observed in 85.7 % of patients . Median neoadjuvant rectal cancer score was 8.7 . CONCLUSIONS With the changed dosing schedule , this regimen was very well tolerated . The tumor pCR and downstaging rates are encouraging and support further clinical investigation of this regimen BACKGROUND Abdominoperineal resection is the st and ard treatment for patients with distal T2 or T3 rectal cancers ; however , the procedure is extensive and mutilating , and alternative treatment strategies are being investigated . We did a prospect i ve observational trial to assess whether high-dose radiotherapy with concomitant chemotherapy followed by observation ( watchful waiting ) was successful for non-surgical management of low rectal cancer . METHODS Patients with primary , resectable , T2 or T3 , N0-N1 adenocarcinoma in the lower 6 cm of the rectum were given chemoradiotherapy ( 60 Gy in 30 fractions to tumour , 50 Gy in 30 fractions to elective lymph node volumes , 5 Gy endorectal brachytherapy boost , and oral tegafur-uracil 300 mg/m(2 ) ) every weekday for 6 weeks . Endoscopies and biopsies of the tumour were done at baseline , throughout the course of treatment ( weeks 2 , 4 , and 6 ) , and 6 weeks after the end of treatment . We allocated patients with complete clinical tumour regression , negative tumour site biopsies , and no nodal or distant metastases on CT and MRI 6 weeks after treatment to the observation group ( watchful waiting ) . We referred all other patients to st and ard surgery . Patients under observation were followed up closely with endoscopies and selected-site biopsies , with surgical resection given for local recurrence . The primary endpoint was local tumour recurrence 1 year after allocation to the observation group . This study is registered with Clinical Trials.gov , number NCT00952926 . Enrolment is closed , but follow-up continues for secondary endpoints . FINDINGS Between Oct 20 , 2009 , and Dec 23 , 2013 , we enrolled 55 patients . Patients were recruited from three surgical units throughout Denmark and treated in one tertiary cancer centre ( Vejle Hospital , Vejle , Denmark ) . Of 51 patients who were eligible , 40 had clinical complete response and were allocated to observation . Median follow-up for local recurrence in the observation group was 23·9 months ( IQR 15·3 - 31·0 ) . Local recurrence in the observation group at 1 year was 15·5 % ( 95 % CI 3·3 - 26·3 ) . The most common acute grade 3 adverse event during treatment was diarrhoea , which affected four ( 8 % ) of 51 patients . Sphincter function in the observation group was excellent , with 18 ( 72 % ) of 25 patients at 1 year and 11 ( 69 % ) of 16 patients at 2 years reporting no faecal incontinence at all and a median Jorge-Wexner score of 0 ( IQR 0 - 0 ) at all timepoints . The most common late toxicity was bleeding from the rectal mucosa ; grade 3 bleeding was reported in two ( 7 % ) in 30 patients at 1 year and one ( 6 % ) of 17 patients at 2 years . There were no unexpected serious adverse reactions or treatment-related deaths . INTERPRETATION High-dose chemoradiotherapy and watchful waiting might be a safe alternative to abdominoperineal resection for patients with distal rectal cancer . FUNDING CIRRO-The Lundbeck Foundation Center for Interventional Research in Radiation Oncology and The Danish Council for Strategic Research PURPOSE The European Organisation for Research and Treatment of Cancer ( EORTC ) trial evaluated the addition of chemotherapy ( CT ) to preoperative radiation ( preop RT ) and the value of postoperative CT for improving the survival in patients with T3 - 4 resectable rectal cancer . Patients were allocated to the following four arms : arm 1 , preop RT 45 Gy in 5 weeks ; arm 2 , preop RT plus two 5-day CT courses ( fluorouracil 350 mg/m2/d and leucovorin 20 mg/m2/d ) in the first and fifth week of RT ; arm 3 , preop RT plus four postoperative CT courses ; and arm 4 , preop RT and CT plus postoperative CT . We investigated the effect of adding CT on the pathologic parameters . PATIENTS AND METHODS One thous and eleven patients were entered onto the trial ; 505 received preop RT ( arms 1 and 3 ) , and 506 received preop RT-CT ( arms 2 and 4 ) . We analyzed the differences in tumor size , tumor node stage , number of retrieved nodes , and histologic features such as lymphatic , venous , and perineural invasions , tumor differentiation , and tumor type . RESULTS After preop RT-CT , tumors were smaller ( P < .0001 ) , had less advanced pT ( P < .001 ) and pN stages ( P < .001 ) , had small numbers of examined nodes ( P = .046 ) , and less frequent LVN invasions ( P < or = .008 ) . Mucinous tumors increased after preop RT-CT ( P < .001 ) . CONCLUSION In patients with rectal cancer , preliminary results of EORTC Trial 22921 indicate that the addition of CT to preop RT induces down-sizing , downstaging , and significant changes in histologic characteristics . Longer follow-up is needed to assess the impact on local control and survival PURPOSE To evaluate the safety and activity of preoperative radiotherapy ( RT ) with concurrent cetuximab , capecitabine , and oxaliplatin in rectal cancer patients . PATIENTS AND METHODS A total of 60 patients with rectal cancer ( T3-T4 or N+ , M1 allowed ) entered the trial at five investigator sites ; the data from 58 patients were assessable . Cetuximab was given as an initial dose of 400 mg/m2 7 days before the start of RT , and then at 250 mg/m2 once weekly during RT ( 50.4 Gy in 28 fractions ) . Capecitabine and oxaliplatin were administered according to an established schedule of oxaliplatin ( 50 mg/m2 on Days 1 , 8 , 22 , and 29 ) and capecitabine ( Days 1 - 14 and 22 - 35 ) at three dose levels : 1,000 , 1,300 , and 1,650 mg/m2/d during the Phase I part of the study . The main endpoint of the Phase II was the pathologic complete response rate . RESULTS Thirteen patients were included in the Phase I part of the study , and the maximal tolerated dose was not reached . Overall , 48 patients were treated at the recommended dose of capecitabine ( 1,650 mg/m2 ) and 45 patients ( 94 % ) underwent surgery . A pathologic complete response was observed in 4 patients ( 9 % ) , and moderate ( n=12 ) , minimal ( n=10 ) , and no tumor regression ( n=2 ) was noted in 24 ( 53 % ) of 45 patients . The mean radiation dose intensity , cetuximab , capecitabine , oxaliplatin was 98 % , 95 % , 94 % , and 94 % , respectively . The incidence of Grade 3 - 4 diarrhea was restricted to 19 % . Postoperative complications of any grade occurred in 33 % of patients . CONCLUSIONS The results of our study have shown that cetuximab can be combined safely with capecitabine and oxaliplatin plus RT . The low pathologic complete response rate achieved should stimulate additional pre clinical investigations to establish the best sequence of triple combinations Purpose : To investigate the feasibility of personalizing chemotherapy in patients with rectal cancer . Methods : Patients with cT3 or cN1 and cM0 rectal cancer were eligible . A set of 6 molecular markers including KRAS , BRAF , and PI3 K mutations and expression of topoisomerase-1 ( Topo-1 ) , ERCC-1 , and thymidylate synthase ( TS ) using immunohistochemistry were performed in a tumor biopsy . All patients were treated with capecitabine 625 to 825 mg/m2/12 h M-F in combination with either irinotecan or oxaliplatin based on Topo-1 and ERCC-1 expression plus either bevacizumab or cetuximab based on the mutation status . All patients received intensity-modulated radiation therapy . A surgery was performed 6 to 8 weeks after the treatment . Results : Fifteen patients ( 94 % ) had T3 tumor and 10 ( 62 % ) N+ disease of 16 patients enrolled . In all patients , the full set of markers was analyzed within 10 days . Seven patients had K-ras mutation , and 4 , 5 , and 10 expressed Topo-1 , ERRC-1 and TS , respectively . All patients had wild-type BRAF and PI3 K tumors . The median time from obtaining informed consent to the treatment period was 18 days and all patients completed the chemoradiation treatment . Fifty percent achieved a complete pathologic response to treatment . Four patients ( 25 % ) developed grade 3 proctitis or diarrhea . There were no relevant surgical complications . Sixty-nine percent of the patients received adjuvant XELOX . Conclusions : The individualization of neoadjuvant chemotherapy in patients with rectal cancer is feasible and leads to a high rate of pathologic response PURPOSE In 1992 , preoperative radiotherapy was considered in France as the st and ard treatment for T3 - 4 rectal cancers . The present r and omized trial compares preoperative radiotherapy with chemoradiotherapy . PATIENTS AND METHODS Patients were eligible if they presented a resectable T3 - 4 , Nx , M0 rectal adenocarcinoma accessible to digital rectal examination . Preoperative radiotherapy with 45 Gy in 25 fractions during 5 weeks was delivered . Concurrent chemotherapy with fluorouracil 350 mg/m2/d during 5 days , together with leucovorin , was administered during the first and fifth week in the experimental arm . Surgery was planned 3 to 10 weeks after the end of radiotherapy . All patients should receive adjuvant chemotherapy with the same fluorouracil/leucovorin regimen . The primary end point of the trial was overall survival . RESULTS A total of 733 patients were eligible . Grade 3 or 4 acute toxicity was more frequent with chemoradiotherapy ( 14.6 % v 2.7 % ; P < .05 ) . There was no difference in sphincter preservation . Complete sterilization of the operative specimen was more frequent with chemoradiotherapy ( 11.4 % v 3.6 % ; P < .05 ) . The 5-year incidence of local recurrence was lower with chemoradiotherapy ( 8.1 % v 16.5 % ; P < .05 ) . Overall 5-year survival in the two groups did not differ . CONCLUSION Preoperative chemoradiotherapy despite a moderate increase in acute toxicity and no impact on overall survival significantly improves local control and is recommended for T3 - 4 , N0 - 2 , M0 adenocarcinoma of the middle and distal rectum PURPOSE To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer . PATIENTS AND METHODS Seven hundred forty-seven patients with resectable , locally advanced ( cT3 - 4 and /or cN1 - 2 ) adenocarcinoma of the mid-low rectum were r and omly assigned to receive pelvic radiation ( 50.4 Gy in 28 daily fractions ) and concomitant infused fluorouracil ( 225 mg/m(2)/d ) either alone ( arm A , n = 379 ) or combined with oxaliplatin ( 60 mg/m(2 ) weekly × 6 ; arm B , n = 368 ) . Overall survival is the primary end point . A protocol -planned analysis of response to preoperative treatment is reported here . RESULTS Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone ( 24 % v 8 % of treated patients ; P < .001 ) . In arm B , 83 % of the patients treated with oxaliplatin had five or more weekly administrations . Ninety-one percent , compared with 97 % in the control arm , received ≥ 45 Gy ( P < .001 ) . Ninety-six percent versus 95 % of patients underwent surgery with similar rates of abdominoperineal resections ( 20 % v 18 % , arm A v arm B ) . The rate of pathologic complete responses was 16 % in both arms ( odds ratio = 0.98 ; 95 % CI , 0.66 to 1.44 ; P = .904 ) . Twenty-six percent versus 29 % of patients had pathologically positive lymph nodes ( arm A v arm B ; P = .447 ) , 46 % versus 44 % had tumor infiltration beyond the muscularis propria ( P = .701 ) , and 7 % versus 4 % had positive circumferential resection margins ( P = .239 ) . Intra-abdominal metastases were found at surgery in 2.9 % versus 0.5 % of patients ( arm A v arm B ; P = .014 ) . CONCLUSION Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy significantly increases toxicity without affecting primary tumor response . Longer follow-up is needed to assess the impact on efficacy end points BACKGROUND KRAS mutation occurs in ∼40 % of locally advanced rectal cancers ( LARCs ) . The multitarget tyrosine kinase inhibitor sorafenib has radiosensitising effects and might improve outcomes for st and ard preoperative chemoradiotherapy in patients with KRAS-mutated LARC . METHODS Adult patients with KRAS-mutated T3/4 and /or N1/2M0 LARC were included in this phase I/II study . The phase I dose-escalation study of capecitabine plus sorafenib and radiotherapy was followed by a phase II study assessing efficacy and safety . Primary end-points were to : establish the maximum tolerated dose of the regimen in phase I ; determine the pathologic complete response ( pCR ) rate in phase II defined as Dworak regression grade 3 and 4 . RESULTS Fifty-four patients were treated at 18 centres in Switzerl and and Hungary ; 40 patients were included in the single-arm phase II study . Recommended doses from phase I comprised radiotherapy ( 45 Gy in 25 fractions over 5 weeks ) with capecitabine 825 mg/m2 twice daily × 33 plus sorafenib 400 mg/d . Median daily dose intensity in phase II was radiotherapy 100 % , capecitabine 98.6 % , and sorafenib 100 % . The pCR rate ( Dworak 3/4 ) was 60 % ( 95 % CI , 43.3 - 75.1 % ) by central independent pathologic review . Sphincter preservation was achieved in 89.5 % , R0 resection in 94.7 % , and downstaging in 81.6 % . The most common grade 3 toxicities during phase II included diarrhoea ( 15.0 % ) , skin toxicity outside radiotherapy field ( 12.5 % ) , pain ( 7.5 % ) , skin toxicity in radiotherapy field , proctitis , fatigue and cardiac ischaemia ( each 5 % ) . CONCLUSIONS Combining sorafenib and st and ard chemoradiotherapy with capecitabine is highly active in patients with KRAS-mutated LARC with acceptable toxicity and deserves further investigation . www . clinical trials.gov : NCT00869570 PURPOSE The potential advantage of high-dose preoperative radiotherapy to increase tumor response and improve the chance of sphincter preservation for low rectal cancer remains controversial . The aim of this trial was to evaluate the role of escalating the dose of preoperative radiation to increase sphincter-saving procedures . PATIENTS AND METHODS Patients with rectal carcinoma located in the lower rectum , staged T2 or T3 , Nx , or M0 with endorectal sonography , and not involving more than two-thirds circumference , were r and omly assigned to one of two groups : preoperative external-beam radiotherapy ( EBRT ; 39 Gy in 13 fractions over 17 days ) versus the same EBRT with boost ( 85 Gy in three fractions ) using endocavitary contact x-ray . RESULTS Between 1996 and 2001 , 88 patients were enrolled onto the study . A significant improvement was seen in favor of the contact x-ray boost for complete clinical response ( 24 % v 2 % ) and for a complete or near-complete sterilization of the operative specimen ( 57 % v 34 % ) . A significant increase in sphincter preservation was observed in the boost group ( 76 % v 44 % ; P = .004 ) . At a median follow-up of 35 months , there was no difference in morbidity , local relapse , and 2-year overall survival . CONCLUSION A dose escalation with endocavitary irradiation provides increased tumor response and sphincter preservation with no detrimental effect on treatment toxicity and early clinical outcome PURPOSE Neoadjuvant chemoradiotherapy is considered a st and ard approach for T3 - 4 M0 rectal cancer . In this situation , we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin . PATIENTS AND METHODS We r and omly assigned patients to receive 5 weeks of treatment with radiotherapy 45 Gy/25 fractions with concurrent capecitabine 800 mg/m(2 ) twice daily 5 days per week ( Cap 45 ) or radiotherapy 50 Gy/25 fractions with capecitabine 800 mg/m(2 ) twice daily 5 days per week and oxaliplatin 50 mg/m(2 ) once weekly ( Capox 50 ) . The primary end point was complete sterilization of the operative specimen ( ypCR ) . RESULTS Five hundred ninety-eight patients were r and omly assigned to receive Cap 45 ( n = 299 ) or Capox 50 ( n = 299 ) . More preoperative grade 3 to 4 toxicity occurred in the Capox 50 group ( 25 v 1 % ; P < .001 ) . Surgery was performed in 98 % of patients in both groups . There were no differences between groups in the rate of conservative surgery ( 75 % ) or postoperative deaths at 60 days ( 0.3 % ) . The ypCR rate was 13.9 % with Cap 45 and 19.2 % with Capox 50 ( P = .09 ) . When ypCR was combined with yp few residual cells , the rate was respectively 28.9 % with Cap 45 and 39.4 % with Capox 50 ( P = .008 ) . The rate of positive circumferential rectal margins ( between 0 and 2 mm ) was 19.3 % with Cap 45 and 9.9 % with Capox 50 ( P = .02 ) . CONCLUSION The benefit of oxaliplatin was not demonstrated and this drug should not be used with concurrent irradiation . Cap 50 merits investigation for T3 - 4 rectal cancers PURPOSE We have previously shown that the addition of cetuximab to chemoradiation therapy failed to improve complete response rates ( pCR ) in rectal cancer . Here we report the long-term results of the cetuximab added to preoperative radiation therapy with capecitabine and oxaliplatin ( CET-CAPOX-RT ) phase 1/2 study that evaluated preoperative chemoradiation with cetuximab , capecitabine , and oxaliplatin in patients with rectal cancer . METHODS AND MATERIAL S The median follow-up was 63 months ( range , 5 - 73 months ) . Sixty patients were enrolled ; 3 patients were excluded due to protocol violation , and 4 died before surgery . Total mesorectal excision was performed in 53 patients , in 85 % ( n=45 ) with curative intention ( M0-status ) . Secondary end points including overall survival ( OS ) disease-free survival ( DFS ) and cancer-specific survival ( CSS ) were calculated . The prognostic value of KRAS mutation status was also assessed . RESULTS Histopathological examination confirmed ypUICC stages 0 ( n=4 ; pCR ) , I ( n=17 ) , II ( n=10 ) , III ( n=14 ) , and IV ( n=8 ) . For patients who underwent surgery ( n=53 ) , OS at 1 , 3 , and 5 years was 88.7 % , 83 % , and 75.5 % , respectively , whereas CSS rates were 94.1 % , 88.1 % , and 78.1 % , respectively . In the 45 patients who were treated with curative intent ( M0 ) , the OS rates at 1 , 3 , and 5 years were 91.1 % , 88.9 % , and 86.7 % , respectively ; whereas CSS rates were 97.6 % , 95.2 % , and 90.3 % , respectively ; and DFS rates were 90.7 % , 88.3 % , and 88.3 % , respectively . We did not find any locoregional failure in patients with M0-status ( n=45 ) . Chronic toxicity was rare . KRAS mutations , as detected in 33.3 % , showed no correlation with the clinicopathological parameters nor significance for either OS ( P=.112 ) , CSS ( P=.264 ) , or DFS ( P=.565 ) . CONCLUSIONS Taken together , chemoradiation therapy combined with cetuximab is safe , feasible , and offers excellent survival rates . KRAS mutation status was not a predictive factor . Importantly , lack of improvement in pCR rate did not translate to poor survival in our clinical trial PURPOSE To assess magnetic resonance imaging ( MRI ) and pathologic staging after neoadjuvant therapy for rectal cancer in a prospect ively enrolled , multicenter study . METHODS In a prospect i ve cohort study , 111 patients who had rectal cancer treated by neoadjuvant therapy were assessed for response by MRI and pathology staging by T , N and circumferential resection margin ( CRM ) status . Tumor regression grade ( TRG ) was also assessed by MRI . Overall survival ( OS ) was estimated by using the Kaplan-Meier product-limit method , and Cox proportional hazards models were used to determine associations between staging of good and poor responders on MRI or pathology and survival outcomes after controlling for patient characteristics . RESULTS On multivariate analysis , the MRI-assessed TRG ( mrTRG ) hazard ratios ( HRs ) were independently significant for survival ( HR , 4.40 ; 95 % CI , 1.65 to 11.7 ) and disease-free survival ( DFS ; HR , 3.28 ; 95 % CI , 1.22 to 8.80 ) . Five-year survival for poor mrTRG was 27 % versus 72 % ( P = .001 ) , and DFS for poor mrTRG was 31 % versus 64 % ( P = .007 ) . Preoperative MRI-predicted CRM independently predicted local recurrence ( LR ; HR , 4.25 ; 95 % CI , 1.45 to 12.51 ) . Five-year survival for poor post-treatment pathologic T stage ( ypT ) was 39 % versus 76 % ( P = .001 ) ; DFS for the same was 38 % versus 84 % ( P = .001 ) ; and LR for the same was 27 % versus 6 % ( P = .018 ) . The 5-year survival for involved pCRM was 30 % versus 59 % ( P = .001 ) ; DFS , 28 versus 62 % ( P = .02 ) ; and LR , 56 % versus 10 % ( P = .001 ) . Pathology node status did not predict outcomes . CONCLUSION MRI assessment of TRG and CRM are imaging markers that predict survival outcomes for good and poor responders and provide an opportunity for the multidisciplinary team to offer additional treatment options before planning definitive surgery . Postoperative histopathology assessment of ypT and CRM but not post-treatment N status were important postsurgical predictors of outcome PURPOSE Although chemoradiotherapy plus resection is considered st and ard treatment for operable rectal carcinoma , the optimal time to administer this therapy is not clear . The NSABP R-03 ( National Surgical Adjuvant Breast and Bowel Project R-03 ) trial compared neoadjuvant versus adjuvant chemoradiotherapy in the treatment of locally advanced rectal carcinoma . PATIENTS AND METHODS Patients with clinical T3 or T4 or node-positive rectal cancer were r and omly assigned to preoperative or postoperative chemoradiotherapy . Chemotherapy consisted of fluorouracil and leucovorin with 45 Gy in 25 fractions with a 5.40-Gy boost within the original margins of treatment . In the preoperative group , surgery was performed within 8 weeks after completion of radiotherapy . In the postoperative group , chemotherapy began after recovery from surgery but no later than 4 weeks after surgery . The primary end points were disease-free survival ( DFS ) and overall survival ( OS ) . RESULTS From August 1993 to June 1999 , 267 patients were r and omly assigned to NSABP R-03 . The intended sample size was 900 patients . Excluding 11 ineligible and two eligible patients without follow-up data , the analysis used data on 123 patients r and omly assigned to preoperative and 131 to postoperative chemoradiotherapy . Surviving patients were observed for a median of 8.4 years . The 5-year DFS for preoperative patients was 64.7 % v 53.4 % for postoperative patients ( P = .011 ) . The 5-year OS for preoperative patients was 74.5 % v 65.6 % for postoperative patients ( P = .065 ) . A complete pathologic response was achieved in 15 % of preoperative patients . No preoperative patient with a complete pathologic response has had a recurrence . CONCLUSION Preoperative chemoradiotherapy , compared with postoperative chemoradiotherapy , significantly improved DFS and showed a trend toward improved OS BACKGROUND Fluorouracil-based chemoradiotherapy is regarded as a st and ard perioperative treatment in locally advanced rectal cancer . We investigated the efficacy and safety of substituting fluorouracil with the oral prodrug capecitabine . METHODS This r and omised , open-label , multicentre , non-inferiority , phase 3 trial began in March , 2002 , as an adjuvant trial comparing capecitabine-based chemoradiotherapy with fluorouracil-based chemoradiotherapy , in patients aged 18 years or older with pathological stage II-III locally advanced rectal cancer from 35 German institutions . Patients in the capecitabine group were scheduled to receive two cycles of capecitabine ( 2500 mg/m(2 ) days 1 - 14 , repeated day 22 ) , followed by chemoradiotherapy ( 50·4 Gy plus capecitabine 1650 mg/m(2 ) days 1 - 38 ) , then three cycles of capecitabine . Patients in the fluorouracil group received two cycles of bolus fluorouracil ( 500 mg/m(2 ) days 1 - 5 , repeated day 29 ) , followed by chemoradiotherapy ( 50·4 Gy plus infusional fluorouracil 225 mg/m(2 ) daily ) , then two cycles of bolus fluorouracil . The protocol was amended in March , 2005 , to allow a neoadjuvant cohort in which patients in the capecitabine group received chemoradiotherapy ( 50·4 Gy plus capecitabine 1650 mg/m(2 ) daily ) followed by radical surgery and five cycles of capecitabine ( 2500 mg/m(2 ) per day for 14 days ) and patients in the fluorouracil group received chemoradiotherapy ( 50·4 Gy plus infusional fluorouracil 1000 mg/m(2 ) days 1 - 5 and 29 - 33 ) followed by radical surgery and four cycles of bolus fluorouracil ( 500 mg/m(2 ) for 5 days ) . Patients were r and omly assigned to treatment group in a 1:1 ratio using permuted blocks , with stratification by centre and tumour stage . The primary endpoint was overall survival ; analyses were done based on all patients with post-r and omisation data . Non-inferiority of capecitabine in terms of 5-year overall survival was tested with a 12·5 % margin . This trial is registered with Clinical Trials.gov , number NCT01500993 . FINDINGS Between March , 2002 , and December , 2007 , 401 patients were r and omly allocated ; 392 patients were evaluable ( 197 in the capecitabine group , 195 in the fluorouracil group ) , with a median follow-up of 52 months ( IQR 41 - 72 ) . 5-year overall survival in the capecitabine group was non-inferior to that in the fluorouracil group ( 76 % [ 95 % CI 67 - 82 ] vs 67 % [ 58 - 74 ] ; p=0·0004 ; post-hoc test for superiority p=0·05 ) . 3-year disease-free survival was 75 % ( 95 % CI 68 - 81 ) in the capecitabine group and 67 % ( 59 - 73 ) in the fluorouracil group ( p=0·07 ) . Similar numbers of patients had local recurrences in each group ( 12 [ 6 % ] in the capecitabine group vs 14 [ 7 % ] in the fluorouracil group , p=0·67 ) , but fewer patients developed distant metastases in the capecitabine group ( 37 [ 19 % ] vs 54 [ 28 % ] ; p=0·04 ) . Diarrhoea was the most common adverse event in both groups ( any grade : 104 [ 53 % ] patients in the capecitabine group vs 85 [ 44 % ] in the fluorouracil group ; grade 3 - 4 : 17 [ 9 % ] vs four [ 2 % ] ) . Patients in the capecitabine group had more h and -foot skin reactions ( 62 [ 31 % ] any grade , four [ 2 % ] grade 3 - 4 vs three [ 2 % ] any grade , no grade 3 - 4 ) , fatigue ( 55 [ 28 % ] any grade , no grade 3 - 4 vs 29 [ 15 % ] , two [ 1 % ] grade 3 - 4 ) , and proctitis ( 31 [ 16 % ] any grade , one [ < 1 % ] grade 3 - 4 vs ten [ 5 % ] , one [ < 1 % ] grade 3 - 4 ) than did those in the fluorouracil group , whereas leucopenia was more frequent with fluorouracil than with capecitabine ( 68 [ 35 % ] any grade , 16 [ 8 % ] grade 3 - 4 vs 50 [ 25 % ] any grade , three [ 2 % ] grade 3 - 4 ) . INTERPRETATION Capecitabine could replace fluorouracil in adjuvant or neoadjuvant chemoradiotherapy regimens for patients with locally advanced rectal cancer . FUNDING Roche Pharma AG ( Grenzach-Wyhlen , Germany ) PURPOSE To assess the feasibility and efficacy of the COX-2 inhibitor celecoxib in conjunction with preoperative chemoradiation for patients with locally advanced rectal cancer in a double blind r and omized phase II study . MATERIAL S AND METHODS Thirty-five patients of the initially planned 80 patients with locally advanced rectal cancer were treated with preoperative radiation ( 45 Gy ; 1.8 Gy/fraction , 5 days/week ) combined with 5-fluorouracil ( continuous infusion , 225 mg/m(2)/day ) and celecoxib ( 2 x 400 mg/day ) or placebo . Pathological response and toxicity of study treatment were evaluated , as well as expression of COX-2 and Ki67 in tumor tissue and IL-6 in plasma as possible molecular correlates and predictors of response to treatment . RESULTS Patients treated with celecoxib tended to show a better response ( 61 % ) when compared to those treated with placebo ( 35 % ) , although not significant ( p=0.13 ) . T-downstaging and N-downstaging were also slightly higher with celecoxib . Plasma IL-6 levels and intratumoral COX2 or Ki67 were altered by chemoradiation , but were not further altered by celecoxib treatment and therefore not useful for prediction of treatment benefit . Celecoxib therapy in conjunction with chemoradiation was not associated with additional toxicity and seemed to help mitigate therapy-related pain . CONCLUSIONS Addition of celecoxib to preoperative chemoradiation is feasible for patients with locally advanced rectal cancer . To study the individual effect of COX-2 inhibitors on pathological response phase III studies are required BACKGROUND Radiation therapy as an adjunct to surgery for rectal cancer has been shown to reduce local recurrence but has not improved survival . In a previous study , combined radiation and chemotherapy improved survival significantly as compared with surgery alone , but not as compared with adjuvant radiation , which many regard as st and ard therapy . We design ed a combination regimen to optimize the contribution of chemotherapy , decrease recurrence , and improve survival as compared with adjuvant radiation alone . METHODS Two hundred four patients with rectal carcinoma that was either deeply invasive or metastatic to regional lymph nodes were r and omly assigned to postoperative radiation alone ( 4500 to 5040 cGy ) or to radiation plus fluorouracil , which was both preceded and followed by a cycle of systemic therapy with fluorouracil plus semustine ( methyl-CCNU ) . RESULTS After a median follow-up of more than seven years , the combined therapy had reduced the recurrence of rectal cancer by 34 percent ( P = 0.0016 ; 95 percent confidence interval , 12 to 50 percent ) . Initial local recurrence was reduced by 46 percent ( P = 0.036 ; 95 percent confidence interval , 2 to 70 percent ) , and distant metastasis by 37 percent ( P = 0.011 ; 95 percent confidence interval , 9 to 57 percent ) . In addition , combined therapy reduced the rate of cancer-related deaths by 36 percent ( P = 0.0071 ; 95 percent confidence interval , 14 to 53 percent ) and the overall death rate by 29 percent ( P = 0.025 ; 95 percent confidence interval , 7 to 45 percent ) . Its acute toxic effects included nausea , vomiting , diarrhea , leukopenia , and thrombocytopenia . These effects were seldom severe . Severe , delayed treatment-related reactions , usually small-bowel obstruction requiring surgery , occurred in 6.7 percent of all patients receiving radiation , and the frequencies of these complications were comparable in both treatment groups . CONCLUSIONS The combination of postoperative local therapy with radiation plus fluorouracil and systemic therapy with a fluorouracil-based regimen significantly and substantively improves the results of therapy for rectal carcinoma with a poor prognosis , as compared with postoperative radiation alone This prospect i ve multicentre study was performed to quantify the number of patients with minimal residual disease ( ypT0–1 ) after neoadjuvant chemoradiotherapy and transanal endoscopic microsurgery ( TEM ) for rectal cancer BACKGROUND EORTC trial 22921 examined the addition of preoperative or postoperative chemotherapy to preoperative radiotherapy in patients with rectal cancer . After a median follow-up of 5 years , chemotherapy-irrespective of timing-significantly improved local control . Adjuvant chemotherapy did not improve survival , but the Kaplan-Meier curves diverged , suggesting possible delayed benefit . Here , we report the up date d long-term results . METHODS We r and omly assigned patients with clinical stage T3 or T4 resectable rectal cancer to receive preoperative radiotherapy with or without concomitant chemotherapy before surgery followed by either adjuvant chemotherapy or surveillance . R and omisation was done using minimisation with factors of institution , sex , T stage , and distance from the tumour to the anal verge . Study coordinators , clinicians , and patients were aware of assignment . Radiotherapy consisted of 45 Gy to the posterior pelvis in 25 fractions of 1·8 Gy over 5 weeks . Each course of chemotherapy consisted of fluorouracil ( 350 mg/m(2 ) per day intravenous bolus ) and folinic acid ( leucovorin ; 20 mg/m(2 ) per day intravenous bolus ) . For preoperative chemotherapy , two courses were given ( during weeks 1 and 5 of radiotherapy ) . Adjuvant chemotherapy was given in four cycles , every 3 weeks . The primary endpoint was overall survival . This analysis was done by intention to treat . The trial is registered with Clinical Trials.gov , number NCT00002523 . FINDINGS 1011 patients were r and omly assigned to treatment between April , 1993 , and March , 2003 ( 252 to preoperative radiotherapy and 253 to each of the other three groups ) . After a median follow-up of 10·4 years ( IQR 7·8 - 13·1 ) , 10-year overall survival was 49·4 % ( 95 % CI 44·6 - 54·1 ) for the preoperative radiotherapy group and 50·7 % ( 45·9 - 55·2 ) for the preoperative radiotherapy and chemotherapy group ( HR 0·99 , 95 % CI 0·83 - 1·18 ; p=0·91 ) . 10-year overall survival was 51·8 % ( 95 % CI 47·0 - 56·4 ) for the adjuvant chemotherapy group and 48·4 % ( 43·6 - 53·0 ) for the surveillance group ( HR 0·91 , 95 % CI 0·77 - 1·09 , p=0·32 ) . 10-year disease-free survival was 44·2 % ( 95 % CI 39·5 - 48·8 ) for the preoperative radiotherapy group and 46·4 % ( 41·7 - 50·9 ) for the preoperative radiotherapy and chemotherapy group ( HR 0·93 , 95 % CI 0·79 - 1·10 ; p=0·38 ) . 10-year disease-free survival was 47·0 % ( 95 % CI 42·2 - 51·6 ) for the adjuvant chemotherapy group and 43·7 % ( 39·1 - 48·2 ) for the surveillance group ( HR 0·91 , 95 % CI 0·77 - 1·08 , p=0·29 ) . At 10 years , cumulative incidence of local relapse was 22·4 % ( 95 % CI 17·1 - 27·6 ) with radiotherapy alone , 11·8 % ( 7·8 - 15·8 ) with neoadjuvant radiotherapy and chemotherapy , 14·5 % ( 10·1 - 18·9 ) with radiotherapy and adjuvant chemotherapy and 11·7 % ( 7·7 - 15·6 ) with both adjuvant and neoadjuvant chemotherapy ( p=0·0017 ) . There was no difference in cumulative incidence of distant metastases ( p=0·52 ) . The frequency of long-term side-effects did not differ between the four groups ( p=0·22 ) . INTERPRETATION Adjuvant fluorouracil-based chemotherapy after preoperative radiotherapy ( with or without chemotherapy ) does not affect disease-free survival or overall survival . Our trial does not support the current practice of adjuvant chemotherapy after preoperative radiotherapy with or without chemotherapy . New treatment strategies incorporating neoadjuvant chemotherapy are required . FUNDING EORTC , US National Cancer Institute , Programme Hospitalier de Recherche Clinique , Ligue contre le Cancer Comité du Doubs PURPOSE Preoperative chemoradiation therapy ( CRT ) is part of the st and ard treatment of locally advanced rectal cancers . Tumor regression at the time of operation is desirable , but not much is known about the relationship between radiation dose and tumor regression . In the present study we estimated radiation dose-response curves for various grade s of tumor regression after preoperative CRT . METHODS AND MATERIAL S A total of 222 patients , treated with consistent chemotherapy and radiation therapy techniques , were considered for the analysis . Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy . Response at the time of operation was evaluated from the histopathologic specimen and grade d on a 5-point scale ( TRG1 - 5 ) . The probability of achieving complete , major , and partial response was analyzed by ordinal logistic regression , and the effect of including clinical parameters in the model was examined . The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50 % response , D50,i , and the normalized dose-response gradient , γ50,i . RESULTS A highly significant dose-response relationship was found ( P=.002 ) . For complete response ( TRG1 ) , the dose-response parameters were D50,TRG1=92.0 Gy ( 95 % confidence interval [ CI ] 79.3 - 144.9 Gy ) , γ50,TRG1=0.982 ( CI 0.533 - 1.429 ) , and for major response ( TRG1 - 2 ) D50,TRG1&2=72.1 Gy ( CI 65.3 - 94.0 Gy ) , γ50,TRG1&2=0.770 ( CI 0.338 - 1.201 ) . Tumor size and N category both had a significant effect on the dose-response relationships . CONCLUSIONS This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4 - 70 Gy , which is higher than the dose range usually considered PURPOSE To evaluate the efficacy and toxicity of preoperative concurrent capecitabine and radiotherapy in the treatment of resectable locally advanced rectal cancer ( LARC ) . MATERIAL S AND METHODS We conducted a phase II trial to assess pathological complete response , tumor downstaging , toxicity and survival of capecitabine ( 825 mg/m(2 ) orally , twice daily ) with radiotherapy ( 50.4 Gy/28 fractions ) in 31 patients with LARC ( cT3/T4 or N+ ) staged by endoscopic ultrasound ( EUS ) . RESULTS Median age was 53 years ; with M : F ratio of 1:1.58 ; 77.4 % had Eastern Cooperative Oncology Group performance status of 1 . EUS showed that 67.7 % of tumors were T3 , 19.4 % were T4 , and 58 % were node positive . Of 30 patients who had surgery , 6.5 % achieved pathological complete remission ( pCR ) . Tumor and nodal downstaging were achieved in 53.9 % and 50 % of patients , respectively . Grade 3/4 toxicities were mainly diarrhea ( 35.5 % ) and proctitis ( 32.3 % ) . Sphincter preservation was achieved in 4/21 ( 15 % ) of patients initially planned for abdominoperineal resection . The median follow-up was 46 months ( Range : 1.47 - 63.9 ) , and the 3-year disease-free and overall survival were 59.8 % and 76.6 % , respectively . CONCLUSION Capecitabine given concurrently with radiation therapy is generally well tolerated , and proved to be an effective radiosensitizer in the neoadjuvant treatment of locally advanced rectal cancer , yielding results comparable to those reported with 5-FU S-1 is a novel , oral fluoropyrimidine and a known radiosensitizer . We conducted a phase I trial to establish a schedule of S-1/irinotecan with st and ard pelvic radiotherapy as a preoperative treatment of locally advanced rectal cancer . Our findings suggest that this new combination is feasible and well tolerable ABSTRACT Aim : The PETACC-6 trial investigates the role of oxaliplatin in addition to preoperative chemoradiation ( CRT ) and adjuvant chemotherapy ( CT ) with capecitabine to improve disease-free survival ( DFS ) in locally advanced rectal cancer . Methods : Patients with rectal adenocarcinoma within 12 cm from the anal verge , T3/4 and /or node-positive , without evidence of metastatic disease , considered either resectable at the time of entry or expected to become resectable , were r and omized to 5 weeks of preoperative CRT with capecitabine , followed by surgery and 6 cycles of adjuvant CT with capecitabine ( st and ard control arm 1 ) or capecitabine + oxaliplatin before and after surgery ( arm 2 ) . 440 DFS events were required to have 80 % power to detect an improvement in 3-year DFS from 65 % to 72 % ( HR = 0.763 ) , with two-sided alpha of 5 % and allowing for an interim analysis for early efficacy at 200 events . Results : 1094 patients were r and omized ( 547 in each arm ) . From 1081 eligible patients , 543 in arm 1 and 528 in arm 2 started preoperative treatment ( 3/528 patients without oxaliplatin in arm 2 ) , and of these 77.3 % and 72.6 % ) patients started postoperative chemotherapy within protocol . In arm 2 , 11.8 % patients did not receive the planned postoperative oxaliplatin . Major reasons for protocol discontinuation were progressive disease ( 3.9 % in arm 1 vs. 3.8 % in arm 2 ) , toxicity ( 7.7 % vs. 16.5 % ) , surgery complication ( 8.7 % vs. 9.1 % ) , patient 's refusal ( 5.9 % vs. 10.8 % ) . At planned interim analysis , the independent data monitoring committee recommended the early release of the results . At a median follow-up of 31months , 124 and 121 DFS events were observed in arm 1 and 2 ( adjusted HR = 1.036 , 95 % CI : 0.81 -1.33 , P = 0.78 ) . 3-year DFS was 74.5 % ( 95 % CI : 70.1 % - 78.3 % ) in arm 1 ( which is higher than anticipated ) vs. 73.9 % ( 95 % CI : 69.5 % - 77.8 % ) in arm 2 ; conditional power under HR = 0.763 is only 7 % . Less locoregional and distant failures were recorded in the experimental arm with oxaliplatin ( 95 in arm 2 vs. 109 in arm 1 ) but a higher rate of deaths without progression ( 26 in arm 2 vs. 15 in arm 1 ) . Conclusions : Interim results at a median follow up of 2.6 y currently indicate no DFS-benefit for the addition of oxaliplatin to capecitabine-based CRT and adjuvant CT . However , with actually only 245 out of the required 440 events , final evaluation can not be done before at least 2 further years follow-up . Disclosure : H.J. Schmoll : has a consultant or advisory relationship to disclose with Roche , Sanofi and Bayer ; has honoraria to disclose from Roche ; has research funding to disclose from Merck and Roche ; K. Haustermans : has research funding to disclose from Roche ; T.J. Price : has a consultant or advisory relationship to disclose with Roche ; R. Hofheinz : has a consultant or advisory relationship to disclose with Roche ; has honoraria and research funding to disclose from Roche ; B. Brenner : has a consultant or advisory relationship to disclose with Sanofi-Aventis ; has research funding to disclose from Sanofi-Aventis ; J. Zalcberg : has a consultant or advisory relationship to disclose with Sanofi-Aventis and Roche ; has honoraria , research funding and other remuneration to disclose from Sanofi-Aventis and Roche . M.P. Lutz : has a consultant or advisory relationship to disclose with Roche ; E. Van Cutsem : has research funding to disclose from Roche and Sanofi . All other authors have declared no conflicts of interest PURPOSE To evaluate neoadjuvant capecitabine/oxaliplatin before chemoradiotherapy ( CRT ) and total mesorectal excision ( TME ) in newly diagnosed patients with magnetic resonance imaging ( MRI ) -defined poor-risk rectal cancer . PATIENTS AND METHODS MRI criteria for poor-risk rectal cancer were tumors within 1 mm of mesorectal fascia ( ie , circumferential resection margin threatened ) , T3 tumors at or below levators , tumors extending > or = 5 mm into perirectal fat , T4 tumors , and T1 - 4N2 tumors . Patients received 12 weeks of neoadjuvant capecitabine/oxaliplatin followed by concomitant capecitabine and radiotherapy . TME was planned 6 weeks after CRT . Postoperatively , patients received another 12 weeks of capecitabine . RESULTS Between November 2001 and August 2004 , 77 eligible patients were recruited . After neoadjuvant capecitabine/oxaliplatin , the radiologic response rate was 88 % . In addition , 86 % of patients had symptomatic responses in a median of 32 days ( ie , just over one cycle of capecitabine/oxaliplatin ) . After CRT , the tumor response rate was increased to 97 % . Three patients remained inoperable . Sixty-seven patients proceeded to TME , and all but one patient had R0 resection . Pathologic complete response was observed in 16 patients ( 24 % ; 95 % CI , 14 % to 36 % ) , and in an additional 32 patients ( 48 % ) , only microscopic tumor foci were found on surgical specimens . Four deaths occurred during neoadjuvant capecitabine/oxaliplatin therapy as a result of pulmonary embolism , ischemic heart disease , sudden death with history of chest pain , and neutropenic colitis . CONCLUSION Capecitabine/oxaliplatin before synchronous CRT and TME results in substantial tumor regression , rapid symptomatic response , and achievement of R0 resection PURPOSE Capecitabine is an attractive radiosensitizer which can be tumor specific . This study was undertaken to evaluate the toxicity and efficacy of oral capecitabine when used with preoperative radiation therapy . METHODS AND MATERIAL S We conducted a prospect i ve Phase II trial to assess the pathologic response , sphincter preservation effect , and acute toxicity of preoperative chemoradiation ( CRT ) in locally advanced ( uT3 - 4/N + ) but resectable adenocarcinoma of the lower two-thirds of the rectum . The radiation dose was 50 Gy over 5 weeks ( 46 Gy to whole pelvis + 4 Gy boost ) , and capecitabine was administered daily at a dose of 1650 mg/m(2 ) during the entire course of radiation therapy . Surgery was performed with st and ardized total mesorectal excision 4 to 6 weeks after completion of CRT and followed by four cycles of capecitabine ( 2500 mg/m(2)/day for 14 days ) . RESULTS Ninety-five patients were entered into this study ; their median age was 55 ( range , 31 - 75 years ) . Ninety ( 95 % ) patients completed preoperative CRT as planned , and complete resection was achieved in 92 of 94 resected cases ( 98 % ) . Downstaging rate was 71 % ( 56/79 ) on endorectal ultrasonography , and it was 76 % ( 71/94 ) on pathology finding . No tumor cell was observed in the specimens of 11 patients ( 12 % ) . Among the 54 whose tumor was located within 5 cm from the anal verge , 40 patients ( 74 % ) underwent sphincter-preserving procedures . Elevation of the distal tumor margin from the anal verge by preoperative CRT was 0.8 + /- 1.3 cm . Grade 3 toxicities were rare ( diarrhea in 3 % and neutropenia in 1 % ) . CONCLUSION Preoperative CRT using capecitabine achieved encouraging rates of tumor downstaging and sphincter preservation with a low toxicity profile Background : Organ preservation has been proposed as an alternative to radical surgery for rectal cancer to reduce morbidity and mortality , and to improve functional outcome . Methods : Locally advanced non-metastatic rectal cancers were identified from a prospect i ve data base . Patients staged ⩾T3 or any stage N+ were referred for neoadjuvant chemoradiotherapy ( CRT ) ( 50–54 Gy and 5-fluorouracil ) , and were reassessed 6–8 weeks post treatment . An active surveillance programme ( ‘ watch and wait ’ ) was offered to patients who were found to have a complete endoluminal response . Transanal excision was performed in patients who were found to have an objective clinical response and in whom a residual ulcer measured ⩽3 cm . Patients were followed up clinical ly , endoscopically and radiologically to assess for local recurrence or disease progression . Results : Of 785 patients with rectal cancer between 2005 and 2015 , 362 had non-metastatic locally advanced tumours treated with neoadjuvant CRT . Sixty out of three hundred and sixty-two ( 16.5 % ) patients were treated with organ-preserving strategies – 10 with ‘ watch and wait ’ and 50 by transanal excision . Fifteen patients were referred for salvage total mesorectal excision post local excision owing to adverse pathological findings . There was no significant difference in overall survival ( 85.6 % vs 93.3 % , P=0.414 ) or disease-free survival rate ( 78.3 % vs 80 % , P=0.846 ) when the outcomes of radical surgery were compared with organ preservation . Tumour regrowth occurred in 4 out of 45 ( 8.9 % ) patients who had organ preservation . Conclusions : Organ preservation for locally advanced rectal cancer is feasible for selected patients who achieve an objective endoluminal response to neoadjuvant CRT . Transanal excision defines the pathological response and refines decision-making Tumor budding is an increasingly important prognostic feature for pathologists to recognize . The aim of this study was to correlate intra-tumoral budding in pre-treatment rectal cancer biopsies with pathological response to neoadjuvant chemoradiotherapy and with long-term outcome . Data from a prospect ively maintained data base were acquired from patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy . Pre-treatment rectal biopsies were retrospectively review ed for evidence of intra-tumoral budding . Multivariate logistic regression was used to identify factors contributing to cancer-specific death , expressed as hazard ratios with 95 % confidence intervals . Of the 185 patients with locally advanced rectal cancer , 89 patients met the eligibility criteria , of whom 18 ( 20 % ) exhibited budding in a pre-treatment tumor biopsy . Intra-tumoral budding predicted a poor pathological response to neoadjuvant chemoradiotherapy ( higher ypT stage , P=0.032 ; lymph node involvement , P=0.018 ; lymphovascular invasion , P=0.004 ; and residual poorly differentiated tumors , P=0.005 ) . No patient with intra-tumoral budding exhibited a tumor regression grade 1 or complete pathological response , providing a 100 % specificity and positive predictive value for non-response to neoadjuvant chemoradiotherapy . Intra-tumoral budding was associated with a lower disease-free 5-year survival rate ( 33 vs 78 % , P<0.001 ) , cancer-specific 5-year survival rate ( 61 vs 87 % , P=0.021 ) and predicted cancer-specific death ( hazard ratio 3.51 , 95 % confidence interval 1.03–11.93 , P=0.040 ) . Intra-tumoral budding at diagnosis of rectal cancer identifies those who will poorly respond to neoadjuvant chemoradiotherapy and those with a poor prognosis PURPOSE Oxaliplatin is a platinum analog and radiosensitizer active in colorectal cancer . We performed a Phase I trial to test the safety and preliminary efficacy of adding oxaliplatin to st and ard preoperative chemoradiation therapy for rectal cancer . METHODS AND MATERIAL S Eligible patients had T3 to T4 rectal adenocarcinoma . Patients received st and ard-dose radiation ( 50.4 Gy for 5.5 weeks ) with concurrent infused 5-fluorouracil ( 5-FU ) at 200 mg/m2 per day , 7 days per week . Oxaliplatin was given three times at 14-day intervals at 55 , 70 , or 85 mg/m2 during the 5.5-week radiation period , before resection . Adjuvant therapy consisted of four cycles of 5-FU ( 500 mg/m2 per week ) with leucovorin ( 500 mg/m2 per week ) given every 6 weeks . The main goals were to identify the maximum tolerated dose of oxaliplatin and the dose-limiting toxicities when given with 5-FU and RT . Secondary goals were to determine resectability , pathologic response , sphincter preservation , and overall survival rates . RESULTS Twenty-one patients were enrolled , 5 at the 55 mg/m2 oxaliplatin dose level , 5 at 70 mg/m2 , and 11 at 85 mg/m2 . All patients were able to complete the preoperative chemoradiation regimen with no dose adjustments . No dose-limiting toxicities or differences in the type or extent of toxicity were noted among the groups . Nineteen patients underwent surgery ( three abdominopelvic resections and 16 low anterior resections ) , for an 84 % sphincter preservation rate . The pathologic complete response rate was 26 % ( 5 patients ) , and minimal microscopic residual tumor was found in 21 % ( 4 additional patients ) . CONCLUSIONS Oxaliplatin was well tolerated at 85 mg/m2 given every 2 weeks in combination with st and ard preoperative chemoradiation for rectal cancer . The rates of major pathologic response and sphincter preservation are promising Predicting responses to immunotherapy Colon cancers with loss-of-function mutations in the mismatch repair ( MMR ) pathway have favorable responses to PD-1 blockade immunotherapy . In a phase 2 clinical trial , Le et al. showed that treatment success is not just limited to colon cancer ( see the Perspective by Goswami and Sharma ) . They found that a wide range of different cancer types with MMR deficiency also responded to PD-1 blockade . The trial included some patients with pancreatic cancer , which is one of the deadliest forms of cancer . The clinical trial is still ongoing , and around 20 % of patients have so far achieved a complete response . MMR deficiency appears to be a biomarker for predicting successful treatment outcomes for several solid tumors and indicates a new therapeutic option for patients harboring MMR-deficient cancers . Science , this issue p. 409 ; see also p. 358 A pan-cancer biomarker is identified that can predict successful response to cancer immunotherapy in human patients . The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations . In a proof-of-concept study , we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor–1 ( PD-1 ) . We have now exp and ed this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair – deficient cancers across 12 different tumor types . Objective radiographic responses were observed in 53 % of patients , and complete responses were achieved in 21 % of patients . Responses were durable , with median progression-free survival and overall survival still not reached . Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor . These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair – deficient cancers make them sensitive to immune checkpoint blockade , regardless of the cancers ’ tissue of origin PURPOSE The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy ( RT ) for patients with rectal cancer is unknown . National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT . PATIENTS AND METHODS Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT ( 45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions ) were r and omly assigned to one of the following chemotherapy regimens : continuous intravenous infusional fluorouracil ( CVI FU ; 225 mg/m(2 ) , 5 days per week ) , with or without intravenous oxaliplatin ( 50 mg/m(2 ) once per week for 5 weeks ) or oral capecitabine ( 825 mg/m(2 ) twice per day , 5 days per week ) , with or without oxaliplatin ( 50 mg/m(2 ) once per week for 5 weeks ) . Before r and om assignment , the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging . The surgical end points were complete pathologic response ( pCR ) , sphincter-sparing surgery , and surgical downstaging ( conversion to sphincter-sparing surgery ) . RESULTS From September 2004 to August 2010 , 1,608 patients were r and omly assigned . No significant differences in the rates of pCR , sphincter-sparing surgery , or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin . Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea ( P < .001 ) . CONCLUSION Administering capecitabine with preoperative RT achieved similar rates of pCR , sphincter-sparing surgery , and surgical downstaging compared with CVI FU . Adding oxaliplatin did not improve surgical outcomes but added significant toxicity . The definitive analysis of local tumor control , disease-free survival , and overall survival will be performed when the protocol -specified number of events has occurred PURPOSE We previously described the prognostic impact of tumor regression grading ( TRG ) on the outcome of patients with rectal carcinoma treated with preoperative chemoradiotherapy ( CRT ) in the CAO/ARO/AIO-94 trial . Here we report long-term results after a median follow-up of 132 months . PATIENTS AND METHODS TRG after preoperative CRT was determined in 386 surgical specimens by the amount of viable tumor cells versus fibrosis , ranging from TRG 4 ( no viable tumor cells ) to TRG 0 ( no signs of regression ) . Clinicopathologic parameters and TRG were correlated to the cumulative incidence of local recurrence , distant metastasis , and disease-free survival ( DFS ) . RESULTS Ten-year cumulative incidence of distant metastasis and DFS were 10.5 % and 89.5 % for patients with TRG 4 ( complete regression ) , 29.3 % and 73.6 % for TRG 2 and 3 ( intermediate regression ) , and 39.6 % and 63 % for TRG 0 and 1 ( poor regression ) , respectively ( P = .005 and P = .008 , respectively ) . On multivariable analysis , residual lymph node metastasis ( ypN+ ) and TRG were the only independent prognostic factors for cumulative incidence of distant metastasis ( P < .001 and P = .035 , respectively ) and DFS ( P < .001 and P = .039 , respectively ) , whereas local recurrence was significantly affected by ypN status ( P < .001 ) and lymphatic invasion ( P = .026 ) . CONCLUSION Complete and intermediate tumor regressions were associated with improved long-term outcome in patients with rectal carcinoma after preoperative CRT independent of clinicopathologic parameters . This classification system needs to be prospect ively tested in multiple data sets to vali date its reproducibility in a wider setting CONTEXT Established as an adjuvant chemotherapy , CapeOX has recently been shown to have radiosensitizer property in a phase I and II studies , with appreciable downstaging and tolerable toxicities . AIMS The study was design ed to evaluate whether the capecitabine-oxaliplatin combination was superior to 5-fluorouracil (5-FU)-leucovorin as radiosensitizer for neoadjuvant chemoradiation in downstaging locally advanced rectal adenocarcinoma and to compare the toxicities between the two arms . SETTING S AND DESIGN Single institutional , double blinded , prospect i ve , noncrossover , r and omized control pilot study . SUBJECTS AND METHODS In arm A ( n = 21 ) , patients received capecitabine ( 1,000 mg/m(2 ) daily ) in twice dailydoseon days 1 - 14 and 25 - 38 and oxaliplatin ( 85 mg/m(2 ) ) intravenous ( IV ) over 2 h , on D1 and D29 . In arm B ( n = 21 ) , patients received leucovorin ( 20 mg/m(2 ) ) and 5-FU ( 350 mg/m(2 ) ) from D1 - 5 and D29 - 33 . Patient in both the arms received concurrent radiation ( 50.4 Gy in 28 # , in conventional fractionation of 1.8 Gy per fraction ) . Six to eight weeks after concurrent chemoradiation , patients underwent assessment and surgery with total mesorectal resection . Postoperatively , adjuvant chemotherapy with m-FOLFOX 6 of 4 months was given to all patients . STATISTICAL ANALYSIS USED Chi-square test was used to compare categorical variables between the groups . RESULTS Objective response rate ( ORR ) in arm A was 80.95 % compared to arm B which had 66.66 % ( P = 0.3055 ) . Pathological complete response ( pCR ) rate of arm A was comparable to arm B ( 23.8 vs 14.28 % , P value = 0.6944 ) . Surgery with R0 resection was possible in 80.95 % cases of arm A compared to 66.66 % cases of arm B ( P = 0.4827 ) . Grade III toxicities were quite comparable between two treatment arms . CONCLUSIONS In terms of ORR , pCR rate , R0 resection , and toxicity profile ; both the arms were comparable |
724 | 30,813,506 | In conclusion , there is strong evidence that air pollution can have adverse effects on cardiovascular function in persons living with CAD . | Persons living with chronic medical conditions ( such as coronary artery disease ( CAD ) ) are thought to be at increased risk when exposed to air pollution .
This systematic review critically evaluated the short-term health effects of air pollution in persons living with CAD . | Background Low heart rate variability ( HRV ) is associated with a higher risk of death in patients with heart disease and in elderly subjects and with a higher incidence of coronary heart disease ( CHD ) in the general population . Methods and Results We studied the predictive value of HRV for CHD and death from several causes in a population study of 14 672 men and women without CHD , aged 45 to 65 , by using the case-cohort design . At baseline , in 1987 to 1989 , 2-minute rhythm strips were recorded . Time-domain measures of HRV were determined in a r and om sample of 900 subjects , for all subjects with incident CHD ( 395 subjects ) , and for all deaths ( 443 subjects ) that occurred through 1993 . Relative rates of incident CHD and cause-specific death in tertiles of HRV were computed with Poisson regression for the case-cohort design . Subjects with low HRV had an adverse cardiovascular risk profile and an elevated risk of incident CHD and death . The increased risk of death could not be attributed to a specific cause and could not be explained by other risk factors . Conclusions Low HRV was associated with increased risk of CHD and death from several causes . It is hypothesized that low HRV is a marker of less favorable health Objective : Days of high ambient carbon dioxide ( CO ) have been associated with increased hospital admissions for cardiac disease . This study was conducted to determine if daily concentrations of CO and fine particulates ( PM2.5 ) are associated with daily changes in heart rate variability . Methods : Each of 36 adults with coronary artery disease had personal exposure to PM2.5 and CO measured along with heart rate variability for one 24-hour period each week for up to 10 weeks . Results : Among those not taking beta-receptor blockers , there was a positive association between the st and ard deviation of the R-to-R intervals and CO ( P = 0.02 ) . No effect was found for PM2.5 . Conclusions : Urban exposure to CO may exert a biologic effect on the heart , which may be modified by medications Objective Exposure to air pollution is associated with increases in cardiovascular morbidity and mortality . This study was undertaken to determine the effect of diesel exhaust inhalation on heart rhythm and heart rate variability in healthy volunteers and patients with coronary heart disease . Design and setting Double-blind r and omised crossover studies in a university teaching hospital . Patients 32 healthy non-smoking volunteers and 20 patients with prior myocardial infa rct ion . Interventions All 52 subjects were exposed for 1 h to dilute diesel exhaust ( particle concentration 300 μg/m3 ) or filtered air . Main outcome measures Heart rhythm and heart rate variability were monitored during and for 24 h after the exposure using continuous ambulatory electrocardiography and assessed using st and ard time and frequency domain analysis . Results No significant arrhythmias occurred during or following exposures . Patients with coronary heart disease had reduced autonomic function in comparison to healthy volunteers , with reduced st and ard deviations of the NN interval ( SDNN , p<0.001 ) and triangular index ( p<0.001 ) . Diesel exhaust did not affect heart rate variability compared with filtered air ( p>0.05 for all ) in healthy volunteers ( SDNN 101±6 vs 91±6 , triangular index 20±1 vs 21±1 ) or patients with coronary heart disease ( SDNN 47±5 vs 38±4 , triangular index 8±1 vs 7±1 ) . Conclusions Brief exposure to dilute diesel exhaust does not alter heart rhythm or heart rate variability in healthy volunteers or well-treated patients with stable coronary heart disease . Autonomic dysfunction does not appear to be a dominant mechanism that can explain the observed excess in cardiovascular events following exposure to combustion-derived air pollution Objective : To measure the inflammatory and autonomic responses of healthy humans and patients with coronary artery disease to controlled concentrations of two specific components of vehicle derived air pollution , carbon particles and sulphur dioxide ( SO2 ) . Methods : Placebo controlled , double blind , r and om order human challenge study examining the effects of carbon particles ( 50 μg/m3 ) and SO2 ( 200 parts per billion ( ppb ) ) on heart rate variability ( HRV ) and circulating markers of inflammation and coagulation in healthy volunteers and patients with stable angina . Results : In healthy volunteers , markers of cardiac vagal control did not fall in response to particle exposure but , compared with the response to air , increased transiently immediately after exposure ( root mean square of successive RR interval differences ( RMSSD ) 15 ( 5 ) ms with carbon particles and 4 ( 3 ) ms ) with air , p < 0.05 ) . SO2 exposure result ed in no immediate change but a significant reduction in HRV markers of cardiac vagal control at four hours ( RMSSD −2 ( 3.6 ) ms with air , −7 ( 2.7 ) ms with SO2 , p < 0.05 ) . No such changes were seen in patients with stable angina . Neither pollutant caused any change in markers of inflammation or coagulation at zero , four , or 24 hours . Conclusion : In healthy volunteers , short term exposure to pure carbon particles does not cause adverse effects on HRV or a systemic inflammatory response . The adverse effects of vehicle derived particulates are likely to be caused by more reactive species found on the particle surface . SO2 exposure does , however , reduce cardiac vagal control , a response that would be expected to increase susceptibility to ventricular arrhythmia Evidence from animal studies suggests that beta-blockers can act within the central nervous system to increase cardiac vagal motoneuron activity . We have attempted to determine whether such an effect is evident in healthy humans , by examining the effects of lipophilic and hydrophilic agents on heart rate variability and cardiac vagal reflexes . A total of 20 healthy volunteers took part in the study . Autonomic studies were performed after 72 h of treatment with placebo , atenolol or metoprolol in a blinded cross-over design . ECG recordings were taken at rest and during mental and orthostatic stress . Heart rate variability was measured in the time and frequency domains . The effects on heart rate of two opposing cardiac vagal reflexes were examined . Trigeminal stimulation causing vagal stimulation , and isometric forearm muscle contraction ( ' muscle heart reflex ' ) causing vagal inhibition , were performed alone and simultaneously . At rest , during mental stress and during trigeminal stimulation , beta-blocker therapy was associated with significantly increased high-frequency beat-to-beat heart rate variability when compared with placebo . There were no significant differences in effects on heart rate or heart rate variability between atenolol and metoprolol . Analysis of the muscle heart reflex , alone and with simultaneous trigeminal stimulation , showed that the magnitude of the R-R interval response was significantly greater after beta-blocker therapy compared with placebo , but the effects of atenolol and metoprolol were equivalent . beta-Blocker therapy increased cardiac vagal activity , as shown by measures of high-frequency heart rate variability and reflex studies . Lipophilic and hydrophilic beta-blockers appeared to be equally efficacious in increasing the cardiac vagal modulation of heart rate Summary Background Long-term exposure to pollution can lead to an increase in the rate of decline of lung function , especially in older individuals and in those with chronic obstructive pulmonary disease ( COPD ) , whereas shorter-term exposure at higher pollution levels has been implicated in causing excess deaths from ischaemic heart disease and exacerbations of COPD . We aim ed to assess the effects on respiratory and cardiovascular responses of walking down a busy street with high levels of pollution compared with walking in a traffic-free area with lower pollution levels in older adults . Methods In this r and omised , crossover study , we recruited men and women aged 60 years and older with angiographically proven stable ischaemic heart disease or stage 2 Global initiative for Obstructive Lung Disease ( GOLD ) COPD who had been clinical ly stable for 6 months , and age-matched healthy volunteers . Individuals with ischaemic heart disease or COPD were recruited from existing data bases or outpatient respiratory and cardiology clinics at the Royal Brompton & Harefield NHS Foundation Trust and age-matched healthy volunteers using advertising and existing data bases . All participants had abstained from smoking for at least 12 months and medications were taken as recommended by participants ' doctors during the study . Participants were r and omly assigned by drawing numbered disks at r and om from a bag to do a 2 h walk either along a commercial street in London ( Oxford Street ) or in an urban park ( Hyde Park ) . Baseline measurements of participants were taken before the walk in the hospital laboratory . During each walk session , black carbon , particulate matter ( PM ) concentrations , ultrafine particles , and nitrogen dioxide ( NO2 ) concentrations were measured . Findings Between October , 2012 , and June , 2014 , we screened 135 participants , of whom 40 healthy volunteers , 40 individuals with COPD , and 39 with ischaemic heart disease were recruited . Concentrations of black carbon , NO2 , PM10 , PM2.5 , and ultrafine particles were higher on Oxford Street than in Hyde Park . Participants with COPD reported more cough ( odds ratio [ OR ] 1·95 , 95 % CI 0·96–3·95 ; p<0·1 ) , sputum ( 3·15 , 1·39–7·13 ; p<0·05 ) , shortness of breath ( 1·86 , 0·97–3·57 ; p<0·1 ) , and wheeze ( 4·00 , 1·52–10·50 ; p<0·05 ) after walking down Oxford Street compared with Hyde Park . In all participants , irrespective of their disease status , walking in Hyde Park led to an increase in lung function ( forced expiratory volume in the first second [ FEV1 ] and forced vital capacity [ FVC ] ) and a decrease in pulse wave velocity ( PWV ) and augmentation index up to 26 h after the walk . By contrast , these beneficial responses were attenuated after walking on Oxford Street . In participants with COPD , a reduction in FEV1 and FVC , and an increase in R5–20 were associated with an increase in during-walk exposure to NO2 , ultrafine particles and PM2.5 , and an increase in PWV and augmentation index with NO2 and ultrafine particles . In healthy volunteers , PWV and augmentation index were associated both with black carbon and ultrafine particles . Interpretation Short-term exposure to traffic pollution prevents the beneficial cardiopulmonary effects of walking in people with COPD , ischaemic heart disease , and those free from chronic cardiopulmonary diseases . Medication use might reduce the adverse effects of air pollution in individuals with ischaemic heart disease . Policies should aim to control ambient levels of air pollution along busy streets in view of these negative health effects . Funding British Heart Foundation Epidemiological studies have shown that air pollution is associated with increased cardiovascular mortality . Although the pathophysiological mechanisms behind this association have remained largely unknown , it has been suggested that changes in cardiac autonomic function may play a role . In this study , we investigated the association between acute carbon monoxide ( CO ) exposure and cardiac autonomic function as measured by heart rate variability ( HRV ) in subjects with stable coronary artery disease . Twenty‐four hour ambulatory electrocardiographic recording with simultaneous continuous personal CO concentration monitoring was performed in six male patients with angiographically verified coronary artery disease three times with 1‐week intervals . Time domain measures of HRV were calculated for 5‐min segments before and during the CO exposure periods . For further analysis CO exposures were divided into low ( ≤2·7 p.p.m . ) and high ( > 2·7 p.p.m . ) CO exposure periods . The mean of maximum CO levels during 61 CO exposure periods was 4·6 p.p.m . ( SD 5·0 p.p.m . ) . High CO exposure was associated with an increase in the square root of the mean of the sum of the squares of differences between adjacent RR intervals ( r‐MSSD ) ( P = 0·034 ) . Heart rate remained unchanged during the CO exposure . In conclusion , acute CO exposure which represented most likely exposure derived from traffic seems to modify cardiac autonomic control in patients with stable coronary artery disease OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Background : Time-series studies have shown short-term temporal associations between low levels of ambient particulate air pollution and adverse health effects . It is not known whether or to what extent this literature is affected by publication bias . Methods : We obtained effect estimates from time-series studies published up to January 2002 . These were summarized and examined for funnel plot asymmetry . We compared summary estimates between single-city and prospect i ve multicity studies . Using 1 multicity study , we examined the sensitivity of summary estimates to alternative lag selection policies . Results : We found evidence for publication bias among single-city studies of daily mortality , hospital admissions for chronic obstructive lung disease ( COPD ) , and incidence of cough symptom , but not for studies of lung function . Statistical correction for this bias reduced summary relative risk estimates for a 10 μg/m3 increment of particulate matter less than 10 μm aerodynamic diameter ( PM10 ) as follows : daily mortality from 1.006 to 1.005 and admissions for COPD from 1.013 to 1.011 ; and odds ratio for cough from 1.025 to 1.015 . Analysis of results from a large multicity study suggested that selection of positive estimates from a range of lags could increase summary estimates for PM10 and daily mortality by up to 130 % above those based on nondirectional approaches . Conclusion : We conclude that publication bias is present in single-city time-series studies of ambient particles . However , after correcting for publication bias statistically , associations between particles and adverse health effects remained positive and precisely estimated . Differential selection of positive lags may also inflate estimates BACKGROUND Recent studies have reported associations between particulate air pollution and daily mortality rates . Population -based , cross-sectional studies of metropolitan areas in the United States have also found associations between particulate air pollution and annual mortality rates , but these studies have been criticized , in part because they did not directly control for cigarette smoking and other health risks . METHODS In this prospect i ve cohort study , we estimated the effects of air pollution on mortality , while controlling for individual risk factors . Survival analysis , including Cox proportional-hazards regression modeling , was conducted with data from a 14-to-16-year mortality follow-up of 8111 adults in six U.S. cities . RESULTS Mortality rates were most strongly associated with cigarette smoking . After adjusting for smoking and other risk factors , we observed statistically significant and robust associations between air pollution and mortality . The adjusted mortality-rate ratio for the most polluted of the cities as compared with the least polluted was 1.26 ( 95 percent confidence interval , 1.08 to 1.47 ) . Air pollution was positively associated with death from lung cancer and cardiopulmonary disease but not with death from other causes considered together . Mortality was most strongly associated with air pollution with fine particulates , including sulfates . CONCLUSIONS Although the effects of other , unmeasured risk factors can not be excluded with certainty , these results suggest that fine-particulate air pollution , or a more complex pollution mixture associated with fine particulate matter , contributes to excess mortality in certain U.S. cities Objectives Epidemiological studies of air pollution on cardiovascular health show associations of cardiac mortality and admissions with exposure to nitrogen dioxide ( NO2 ) at low concentrations . These associations could be causal or NO2 could be acting as a surrogate measure for another air pollutant , most likely ultrafine particles . No studies of cardiac susceptibility to acute exposure to NO2 have been undertaken . Methods R and omised controlled exposures to NO2 ( 400 ppb for 1 h ) and air in subjects with coronary heart disease and impaired left ventricular systolic function not taking β adrenoceptor blocking drugs . Results There were no significant changes in heart rate , blood pressure , leucocyte coping capacity or any heart rate variability measure following NO2 exposure compared with air . Conclusion These findings suggest that NO2 does not affect heart rate variability at these concentrations ( which are high for urban background levels ) and in the absence of other pollutants . While a synergistic effect has not been ruled out , these data lend support to the idea that the epidemiological data associating cardiac outcomes with NO2 are more likely due to an associated pollutant rather than NO2 itself Time-series , cross-sectional , and prospect i ve cohort studies have observed associations between mortality and particulate air pollution but have been limited by ecologic design or small number of subjects or study areas . The present study evaluates effects of particulate air pollution on mortality using data from a large cohort drawn from many study areas . We linked ambient air pollution data from 151 U.S. metropolitan areas in 1980 with individual risk factor on 552,138 adults who resided in these areas when enrolled in a prospect i ve study in 1982 . Deaths were ascertained through December , 1989 . Exposure to sulfate and fine particulate air pollution , which is primarily from fossil fuel combustion , was estimated from national data bases . The relationships of air pollution to all-cause , lung cancer , and cardiopulmonary mortality was examined using multivariate analysis which controlled for smoking , education , and other risk factors . Although small compared with cigarette smoking , an association between mortality and particulate air pollution was observed . Adjusted relative risk ratios ( and 95 % confidence intervals ) of all-cause mortality for the most polluted areas compared with the least polluted equaled 1.15 ( 1.09 to 1.22 ) and 1.17 ( 1.09 to 1.26 ) when using sulfate and fine particulate measures respectively . Particulate air pollution was associated with cardiopulmonary and lung cancer mortality but not with mortality due to other causes . Increased mortality is associated with sulfate and fine particulate air pollution at levels commonly found in U.S. cities . The increase in risk is not attributable to tobacco smoking , although other unmeasured correlates of pollution can not be excluded with certainty BACKGROUND Exposure to air pollution from traffic is associated with adverse cardiovascular events . The mechanisms for this association are unknown . We conducted a controlled exposure to dilute diesel exhaust in patients with stable coronary heart disease to determine the direct effect of air pollution on myocardial , vascular , and fibrinolytic function . METHODS In a double-blind , r and omized , crossover study , 20 men with prior myocardial infa rct ion were exposed , in two separate sessions , to dilute diesel exhaust ( 300 mug per cubic meter ) or filtered air for 1 hour during periods of rest and moderate exercise in a controlled-exposure facility . During the exposure , myocardial ischemia was quantified by ST-segment analysis using continuous 12-lead electrocardiography . Six hours after exposure , vasomotor and fibrinolytic function were assessed by means of intraarterial agonist infusions . RESULTS During both exposure sessions , the heart rate increased with exercise ( P<0.001 ) ; the increase was similar during exposure to diesel exhaust and exposure to filtered air ( P=0.67 ) . Exercise-induced ST-segment depression was present in all patients , but there was a greater increase in the ischemic burden during exposure to diesel exhaust ( -22+/-4 vs. -8+/-6 millivolt seconds , P<0.001 ) . Exposure to diesel exhaust did not aggravate preexisting vasomotor dysfunction , but it did reduce the acute release of endothelial tissue plasminogen activator ( P=0.009 ; 35 % decrease in the area under the curve ) . CONCLUSIONS Brief exposure to dilute diesel exhaust promotes myocardial ischemia and inhibits endogenous fibrinolytic capacity in men with stable coronary heart disease . Our findings point to ischemic and thrombotic mechanisms that may explain in part the observation that exposure to combustion-derived air pollution is associated with adverse cardiovascular events . ( Clinical Trials.gov number , NCT00437138 [ Clinical Trials.gov ] . ) OBJECTIVE To assess the effects of exposure to 4 % and 6 % carboxyhemoglobin on ventricular arrhythmias in patients with coronary artery disease . DESIGN R and omized , double-blind , crossover design . SETTING Exercise laboratory with an environmentally controlled exposure . PATIENTS Forty-one nonsmokers with documented coronary artery disease . INTERVENTION On day 1 , a training session with no exposure , the baseline carboxyhemoglobin level was measured , and a supine bicycle exercise test was done . On days 2 to 4 , patients were exposed to room air , 100 ppm carbon monoxide ( target , 4 % carboxyhemoglobin ) or 200 ppm carbon monoxide ( target , 6 % carboxyhemoglobin ) , and they then did supine bicycle exercise with radionuclide ventriculography . Ambulatory electrocardiogram recordings were made during the 4 consecutive days to determine the frequency of ventricular premature depolarization ( VPD ) at various intervals . MEASUREMENTS AND MAIN RESULTS The frequency of single VPD/h was significantly greater on the 6 % carboxyhemoglobin day than on the room air day during the exercise period ( 167.72 + /- 37.99 for 6 % carboxyhemoglobin compared with 127.32 + /- 28.22 for room air , P = 0.03 ) . During exercise , the frequency of multiple VPD/h was greater on the 6 % carboxyhemoglobin day compared with room air ( 9.59 + /- 3.70 on the 6 % carboxyhemoglobin compared with 3.18 + /- 1.67 on room air , P = 0.02 ) . Patients who developed increased single VPD during exercise on the 6 % carboxyhemoglobin day were significantly older than those who had no increased arrhythmia , whereas patients who developed complex arrhythmias were also older and , in addition , exercised longer and had a higher peak workload during exercise . CONCLUSION The number and complexity of ventricular arrhythmias increases significantly during exercise after carbon monoxide exposure producing 6 % carboxyhemoglobin compared with room air but not after exposure producing 4 % carboxyhemoglobin |
725 | 31,267,981 | Conclusions Low to modest and mixed evidence suggests that when compared with traditional education , virtual patients can more effectively improve skills , and at least as effectively improve knowledge .
The skills that improved were clinical reasoning , procedural skills , and a mix of procedural and team skills .
We found evidence of effectiveness in both high-income and low- and middle-income countries , demonstrating the global applicability of virtual patients . | Background Virtual patients are interactive digital simulations of clinical scenarios for the purpose of health professions education .
There is no current collated evidence on the effectiveness of this form of education .
Objective The goal of this study was to evaluate the effectiveness of virtual patients compared with traditional education , blended with traditional education , compared with other types of digital education , and design variants of virtual patients in health professions education .
The outcomes of interest were knowledge , skills , attitudes , and satisfaction . | Background Most of the many computer re sources used in clinical teaching of dermatology and venereology for medical undergraduates are information-oriented and focus mostly on finding a " correct " multiple-choice alternative or free-text answer . We wanted to create an interactive computer program , which facilitates not only factual recall but also clinical reasoning . Methods Through continuous interaction with students , a new computerised interactive case simulation system , NUDOV , was developed . It is based on authentic cases and contains images of real patients , actors and healthcare providers . The student selects a patient and proposes questions for medical history , examines the skin , and suggests investigations , diagnosis , differential diagnoses and further management . Feedback is given by comparing the user 's own suggestions with those of a specialist . In addition , a log file of the student 's actions is recorded . The program includes a large number of images , video clips and Internet links . It was evaluated with a student question naire and by r and omising medical students to conventional teaching ( n = 85 ) or conventional teaching plus NUDOV ( n = 31 ) and comparing the results of the two groups in a final written examination . Results The question naire showed that 90 % of the NUDOV students stated that the program facilitated their learning to a large/very large extent , and 71 % reported that extensive working with authentic computerised cases made it easier to underst and and learn about diseases and their management . The layout , user-friendliness and feedback concept were judged as good/very good by 87 % , 97 % , and 100 % , respectively . Log files revealed that the students , in general , worked with each case for 60–90 min . However , the intervention group did not score significantly better than the control group in the written examination . Conclusion We created a computerised case simulation program allowing students to manage patients in a non-linear format supporting the clinical reasoning process . The student gets feedback through comparison with a specialist , eliminating the need for external scoring or correction . The model also permits discussion of case processing , since all transactions are stored in a log file . The program was highly appreciated by the students , but did not significantly improve their performance in the written final examination Introduction Physician empathy is a complex phenomenon known to improve illness outcomes ; however , few tools are available for deliberate practice of empathy . We used a virtual patient ( VP ) to teach empathic communication to first-year medical students . We then evaluated students ’ verbal empathy in a st and ardized patient ( SP ) interaction . Methods Seventy medical students , r and omly assigned to 3 separate study groups , interacted with ( 1 ) a control VP portraying depression , ( 2 ) a VP with a backstory simulating patient shadowing , or ( 3 ) a VP able to give immediate feedback about empathic communication ( empathy-feedback VP ) . Subsequently , the students interviewed an SP portraying a scenario that included opportunities to express empathy . All SP interviews were recorded and transcribed . The study outcomes were ( 1 ) the students ’ verbal response to the empathic opportunities presented by the SP , as coded by reliable assessors using the Empathic Communication Coding System , and ( 2 ) the students ’ responses as coded by the SPs , using a communication checklist . Results There were no significant differences in student demographics between groups . The students who interacted with the empathy-feedback VP showed higher empathy in the SP interview than did the students in the backstory VP and the control VP groups [ mean ( SD ) empathy scores coded on a 0–6 scale were 2.91 ( 0.16 ) vs. 2.20 ( 0.22 ) and 2.27 ( 0.21 ) , respectively ) . The difference in scores was significant only for the empathy-feedback VP versus the backstory VP group ( P = 0.027 ) . The SPs rated the empathy-feedback and the backstory VP groups significantly higher than the control VP group on offering empathic statements ( P < 0.0001 ) , appearing warm and caring ( P = 0.015 ) , and forming rapport ( P = 0.004 ) . Conclusions Feedback on empathy in a VP interaction increased students ’ empathy in encounters with SPs , as rated by trained assessors , whereas a simulation of patient shadowing did not . Both VP interventions increased students ’ empathy as rated by SPs , compared with the control VP group Objective To improve pain management practice s , we developed an online interactive continuing education ( CE ) program for primary care providers ( PCPs ) . This program follows the flow of clinical decision-making through simulated cases at critical pain treatment points along the pain treatment continuum . Design A r and omized controlled trial was conducted to test the efficacy of this program . Participants were r and omized to either the experimental condition or the control condition ( online , text-based CE program ) . Subjects A total of 238 primary care providers were recruited through hospitals , professional newsletters , and pain conferences . Results Participants in both conditions reported significantly improved scores on knowledge ( KNOW-PAIN 50 ) , attitudes ( CAOS ) , and pain practice behaviors ( PPBS ) scales over the four-month study . The experimental condition showed significantly greater change over time on the tamper-resistant formulations ( TRFs ) of opioids and dosing CAOS subscale compared with the control condition . Post hoc comparisons suggested that participants in the experimental condition were less likely to endorse use of opioid TRFs over time compared with the control condition . Exploratory analyses for potential moderators indicated a significant three-way interaction with time , condition , and discipline ( i.e. , physician vs other ) for the impediments and concerns attitudes subscale and the early refill behaviors subscale . Post hoc comparisons indicated that physicians in the experimental condition exhibited the greatest change in attitudes and the nonphysicians exhibited the greatest change in reported behaviors in response to requests for early refills . Conclusions Findings suggest online CE programs may positively impact PCPs ' knowledge , attitudes , and pain practice behaviors but provide minimal evidence for the value of including interactivity Background The concept of virtual patients ( VPs ) encompasses a great variety of predominantly case-based e-learning modules with different complexity and fidelity levels . Methods for effective placement of VPs in the process of medical education are sought . The aim of this study was to determine whether the introduction of a voluntary virtual patients module into a basic life support with an automated external defibrillator ( BLS-AED ) course improved the knowledge and skills of students taking the course . Methods Half of the students were r and omly assigned to an experimental group and given voluntary access to a virtual patient module consisting of six cases presenting BLS-AED knowledge and skills . Pre- and post-course knowledge tests and skills assessment s were performed , as well as a survey of students ' satisfaction with the VP usage . In addition , time spent using the virtual patient system , percentage of screen cards viewed and scores in the formative questions in the VP system throughout the course were traced and recorded . Results The study was conducted over a six week period and involved 226 first year medical students . The voluntary module was used by 61 ( 54 % ) of the 114 entitled study participants . The group that used VPs demonstrated better results in knowledge acquisition and in some key BLS-AED action skills than the group without access , or those students from the experimental group deliberately not using virtual patients . Most of the students rated the combination of VPs and corresponding teaching events positively . Conclusions The overall positive reaction of students and encouraging results in knowledge and skills acquisition suggest that the usage of virtual patients in a BLS-AED course on a voluntary basis is feasible and should be further investigated Objectives To compare medical students ’ and residents ’ knowledge retention of assessment , diagnosis and treatment procedures , as well as a learning experience , of patients with spinal trauma after training with either a Virtual Patient case or a video-recorded traditional lecture . Methods A total of 170 volunteers ( 85 medical students and 85 residents in orthopedic surgery ) were r and omly allocated ( stratified for student/resident and gender ) to either a video-recorded st and ard lecture or a Virtual Patient-based training session where they interactively assessed a clinical case portraying a motorcycle accident . The knowledge retention was assessed by a test immediately following the educational intervention and repeated after a minimum of 2 months . Participants ’ learning experiences were evaluated with exit question naires . A repeated- measures analysis of variance was applied on knowledge scores . A total of 81 % ( n = 138 ) of the participants completed both tests . Results There was a small but significant decline in first and second test results for both groups ( F(1 , 135 ) = 18.154 , p = 0.00 ) . However , no significant differences in short-term and long-term knowledge retention were observed between the two teaching methods . The Virtual Patient group reported higher learning experience levels in engagement , stimulation , general perception , and expectations . Conclusions Participants ’ levels engagement were reported in favor of the VP format . Similar knowledge retention was achieved through either a Virtual Patient or a recorded lecture Background E-learning and blended learning approaches gain more and more popularity in emergency medicine curricula . So far , little data is available on the impact of such approaches on procedural learning and skill acquisition and their comparison with traditional approaches . Objective This study investigated the impact of a blended learning approach , including Web-based virtual patients ( VPs ) and st and ard pediatric basic life support ( PBLS ) training , on procedural knowledge , objective performance , and self- assessment . Methods A total of 57 medical students were r and omly assigned to an intervention group ( n=30 ) and a control group ( n=27 ) . Both groups received paper h and outs in preparation of simulation-based PBLS training . The intervention group additionally completed two Web-based VPs with embedded video clips . Measurements were taken at r and omization ( t0 ) , after the preparation period ( t1 ) , and after h and s-on training ( t2 ) . Clinical decision-making skills and procedural knowledge were assessed at t0 and t1 . PBLS performance was scored regarding adherence to the correct algorithm , conformance to temporal dem and s , and the quality of procedural steps at t1 and t2 . Participants ’ self- assessment s were recorded in all three measurements . Results Procedural knowledge of the intervention group was significantly superior to that of the control group at t1 . At t2 , the intervention group showed significantly better adherence to the algorithm and temporal dem and s , and better procedural quality of PBLS in objective measures than did the control group . These aspects differed between the groups even at t1 ( after VPs , prior to practical training ) . Self- assessment s differed significantly only at t1 in favor of the intervention group . Conclusions Training with VPs combined with h and s-on training improves PBLS performance as judged by objective measures PURPOSE To assess the performance of interprofessional teams of radiologists , technologists , and nurses trained with high-fidelity h and s-on ( HO ) simulation and computer-based ( CB ) simulation training for contrast reaction management ( CR ) and teamwork skills ( TS ) . METHODS Nurses , technologists , and radiology residents were r and omized into 11 teams of three ( one of each ) . Six teams underwent HO training and five underwent CB training for CR and TS . Participants took written tests before and after training and were further tested using a high-fidelity simulation scenario . RESULTS HO and CB groups scored similarly on all written tests and each showed improvement after training ( P = .002 and P = .018 , respectively ) . During the final scenario test , HO teams tended to receive higher grade s than CB teams on CR ( 95 % versus 81 % , P = .17 ) and made fewer errors in epinephrine administration ( 0/6 versus 2/5 , P = .18 ) . HO and CB teams scored similarly on TS ( 51 % versus 52 % , P = .66 ) , but overall scores were lower for TS than for CR skills in both the HO ( P = .03 ) and CB teams ( P = .06 ) . HO training was more highly rated than CB as an effective educational tool ( P = .01 ) and for effectiveness at teaching CR and team communication skills ( P = .02 ) . CONCLUSIONS High-fidelity simulation can be used to both train and test interprofessional teams of radiologists , technologists , and nurses for both CR and TS and is more highly rated as an effective educational tool by participants than similar CB training . However , a single session of either type of training may be inadequate for mastering TS Aim The Virtual Ophthalmology Clinic ( VOC ) is an interactive web-based teaching module , with special emphasis on history taking and clinical reasoning skills . The purpose of this study was to determine the impact of VOC on medical students ’ learning . Methods A r and omised controlled trial ( RCT ) was conducted with medical students from the University of Sydney ( n=188 ) who were r and omly assigned into either an experimental ( n=93 ) or a control group ( n=95 ) . A pre- and post-test and student satisfaction question naire were administered . Twelve months later a follow-up test was conducted to determine the long-term retention rate of graduates . Results There was a statistically significant ( P<0.001 ) within-subject improvement pre- to post rotation in the number of correctly answered questions for both the control and experimental groups ( mean improvement for control 10 % , 95 % CI 1.3–2.6 , and for experimental 17.5 % , 95 % CI 3.0–4.0 ) . The improvement was significantly greater in the experimental group ( mean difference in improvement between groups 7.5 % , 95 % CI 0.8–2.3 , P<0.001 ) . At 12 months follow-up testing , the experimental group scored on average 1.6 ( 8 % ) ( 95%CI 0.4 to 2.7 , P=0.007 ) higher than the controls . Conclusion On the basis of a statistically significant improvement in academic performance and highly positive student feedback , the implementation of VOC may provide a means to address challenges to ophthalmic learning outcomes in an already crowded medical curriculum We intended to clarify the influence of student academic ability on the effectiveness of CAI , using data of a study to assess the effectiveness of a new type of CAI software , cyberPatient ( CP ) , at Kochi Medical School ( KMS ) . A total of 59 third-year students were r and omly assigned to four groups : Group-1 used a textbook for self-instruction , Group-2 used CP , Group-3 used both types of learning material s , and Group-4 did not learn . Learning performance was evaluated by multiple-choice examination and OSCE . In order to clarify the influence of students ' academic ability on the effectiveness of CAI , statistical analyses were conducted , assigning students as either high or medium or low performance students . High performance students from Group-1 , -2 and -3 did not differ significantly in test performance after self-instruction . However , low performance students in Group-1 scored significantly lower than those in Group-2 and -3 . All students in Group-2 and -3 reported that CP stimulated willingness to learn and assisted underst and ing . The present analysis suggested that effectiveness of CAI might be associated with the academic ability of students A prospect i ve study was performed to better define the role of computers in teaching radiology to medical students . Two hundred twenty-five 3rd-year students were r and omly assigned to one of four groups and exposed to 10 radiology cases as well as to a voluntary weekly radiology lecture . Group A used computer-based cases with interactive elements ; group B used computer-based cases without interactive elements ; group C used paper-based cases with interactive elements ; and group D was not exposed to the cases and served as a control group . On a multiple-choice question test , groups A , B , and C showed significant improvement ( + 11.2 % , + 15.1 % , and + 13.0 % , respectively ) , whereas group D did not ( + 0.6 % ) . On an image interpretation test , group A showed the most improvement ( + 15.7 % [ P < .001 ] ) , followed by group B ( + 15.1 % [ P < .01 ] ) and group C ( + 10.2 % [ P < .05 ] ) ; group D showed no significant improvement ( + 8.5 % ) . No significant differences in the learning outcome were found between the two interactive groups ( computer based and paper based ) . Computer-based teaching with case studies ( with or without interactivity ) improves students ' problem-solving ability in radiology Background : Virtual patients ( VPs ) , high-fidelity simulators and st and ardized patients are powerful educational interventions leading to effective learning and supporting knowledge retention . Aim : This study explored the variations in retention with VP versus regular learning activities . Method : We conducted a r and omized controlled study on early and delayed assessment results of 49 students using VP for learning and examination of haematology and cardiology topics in an Internal Medicine course , by means of a 0–10 scoring rubric . Results : The mean difference for early assessment with VP ( study – control mean score ) was 1.43 ( 95 % confidence interval ( CI ) 0.96 , 1.91 ; p < 0.001 ) for haematology and 1.34 ( 95 % CI 0.93 , 1.76 ; p < 0.001 ) for cardiology . In regular exams , the mean score difference was 2.21 ( 95 % CI 1.3 , 3.1 ; p < 0.001 ) and 1.52 ( 95 % CI 0.76 , 2.28 ; p < 0.001 ) , respectively . With delayed assessment s , the difference in mean score for Web-SP was 1.48 ( 95 % CI 1.09 , 1.86 ; p < 0.001 ) , haematology and 1.16 ( 95 % CI 0.74 , 1.58 ; p < 0.001 ) , cardiology ; for regular exams the figures were 1.96 ( 95 % CI 0.93 , 2.98 ; p < 0.001 ) and 1.74 ( 95 % CI 0.89 , 2.58 ; p < 0.001 ) . The effect size ranged from 0.5 to 0.8 . Conclusion : Our results indicate better retention with VP than with traditional learning methods Purpose To evaluate a five-year experience ( 1995–2000 ) developing and integrating computer cases into a required clerkship . Method In Study 1 , 54 volunteer students were r and omly assigned to study articles , a paper case , or a computer case on low back pain/kidney stones . Students were given an exam immediately after the exercise and one week later . In Study 2 , 325 clerkship students were asked to select and complete two computer cases or to prepare assignments on unrelated topics . Among the cases offered were two test cases on low back pain/kidney stones and pneumonia . Questions specific to the computer test cases ( CC ) and other noncomputer cases ( NCC ) were in the final exam . Exam scores related to CC questions and NCC questions were compared between the groups of students who did and did not complete the computer cases . Students also rated the computer cases on a question naire . Results In Study 1 , reading articles required the most time and received the most negative comments . The students who completed the computer case scored the best on the exam one week later . In Study 2 , the students who completed the two computer cases scored significantly higher on the CC questions than did students who studied only one or none of the computer cases ( p < .001 ) . There was no difference among groups for the NCC scores ( p = .76 ) . Students rated the computer cases with a mean of 6 on a seven-point scale ( 7 = strongly agree ) . Conclusion Computer cases are effective learning tools , are well-received by students , and can be successfully integrated into existing clerkships The purpose of this study was to explore the effect of actively constructing virtual patient ( VP ) cases compared with solving VP cases on knowledge gains , skills transfer and time spent on cases . Forty-five fourth-year medical students were r and omized to constructing ( VP-construction , n = 23 ) or solving ( VP-solving , n = 22 ) four cardiopulmonary VP cases . Whereas the VP-solving group solved the cases , the VP-construction group only received the final diagnosis and had to complete the history , physical findings , and lab results . After a week , participants completed a transfer test involving two st and ardized patients representing cardiopulmonary cases . Performances on the transfer test were video-recorded and assessed by two blinded raters using the Reporter , Interpreter , Manager , Educator ( RIME ) framework . Thirty-nine participants completed the transfer test . The VP-construction group spent significantly more time on the VP cases compared with the VP-solving group , p = 0.002 . There were no significant differences in RIME scores between the VP-construction group and VP-solving group , p = 0.54.In conclusion , engaging novice students in active VP case construction may be more time consuming than solving VP cases , without result ing in superior skills transfer Simulation games are becoming increasingly popular in education , but more insight in their critical design features is needed . This study investigated the effects of fidelity of open patient cases in adjunct to an instructional e-module on students ’ cognitive skills and motivation . We set up a three-group r and omized post-test-only design : a control group working on an e-module ; a cases group , combining the e-module with low-fidelity text-based patient cases , and a game group , combining the e-module with a high-fidelity simulation game with the same cases . Participants completed question naires on cognitive load and motivation . After a 4-week study period , blinded assessors rated students ’ cognitive emergency care skills in two mannequin-based scenarios . In total 61 students participated and were assessed ; 16 control group students , 20 cases students and 25 game students . Learning time was 2 h longer for the cases and game groups than for the control group . Acquired cognitive skills did not differ between groups . The game group experienced higher intrinsic and germane cognitive load than the cases group ( p = 0.03 and 0.01 ) and felt more engaged ( p < 0.001 ) . Students did not profit from working on open cases ( in adjunct to an e-module ) , which nonetheless challenged them to study longer . The e-module appeared to be very effective , while the high-fidelity game , although engaging , probably distracted students and impeded learning . Medical educators design ing motivating and effective skills training for novices should align case complexity and fidelity with students ’ proficiency level . The relation between case-fidelity , motivation and skills development is an important field for further study Background Virtual patient simulation has grown substantially in health care education . A virtual patient simulation was developed as a refresher training course to reinforce nursing clinical performance in assessing and managing deteriorating patients . Objective The objective of this study was to describe the development of the virtual patient simulation and evaluate its efficacy , by comparing with a conventional mannequin-based simulation , for improving the nursing students ’ performances in assessing and managing patients with clinical deterioration . Methods A r and omized controlled study was conducted with 57 third-year nursing students who were recruited through email . After a baseline evaluation of all participants ’ clinical performance in a simulated environment , the experimental group received a 2-hour fully automated virtual patient simulation while the control group received 2-hour facilitator-led mannequin-based simulation training . All participants were then re-tested one day ( first posttest ) and 2.5 months ( second posttest ) after the intervention . The participants from the experimental group completed a survey to evaluate their learning experiences with the newly developed virtual patient simulation . Results Compared to their baseline scores , both experimental and control groups demonstrated significant improvements ( P<.001 ) in first and second post-test scores . While the experimental group had significantly lower ( P<.05 ) second post-test scores compared with the first post-test scores , no significant difference ( P=.94 ) was found between these two scores for the control group . The scores between groups did not differ significantly over time ( P=.17 ) . The virtual patient simulation was rated positively . Conclusions A virtual patient simulation for a refreshing training course on assessing and managing clinical deterioration was developed . Although the r and omized controlled study did not show that the virtual patient simulation was superior to mannequin-based simulation , both simulations have demonstrated to be effective refresher learning strategies for improving nursing students ’ clinical performance . Given the greater re source requirements of mannequin-based simulation , the virtual patient simulation provides a more promising alternative learning strategy to mitigate the decay of clinical performance over time OBJECTIVE To determine whether an advanced cardiac life support ( ACLS ) computer simulation program improves retention of ACLS guidelines more effectively than textbook review . DESIGN R and omized , controlled trial . SETTING Academic medical center . PARTICIPANTS Forty-five anesthesia residents and faculty tested 10 to 11 months after ACLS provider course training . INTERVENTION Participants were r and omized and asked to prepare for a mock resuscitation ( Mega Code ) with either textbooks or a computerized ACLS simulation program . MAIN OUTCOME MEASURE Performance on a st and ardized Mega Code examination that required application of supraventricular tachycardia , ventricular fibrillation , and second-degree Type II atrioventricular block algorithms . Mega Code sessions were administered by an instructor who was blinded as to the subject group . The sessions were videotaped and scored by two evaluators who also were blinded as to the subject group . RESULTS Participants who used the ACLS simulation program scored significantly higher ( mean 34.9 + /- 5.0 [ SD ] of 47 possible points ) than participants who review ed using a textbook ( 29.2 + /- 4.9 ) ; p < .001 . Pass-fail rates for the algorithms were also higher for the group that review ed with the simulator ( mean 2.5 + /- 0.5 of 3 possible passes ) than the group that used the textbook ( 1.6 + /- 1.0 ) ; p = .001 . CONCLUSIONS Use of a computerized ACLS simulation program improves retention of ACLS guidelines better than textbook review Objective This pilot study investigates the impact of an online , interactive simulation involving an Arab American Muslim patient on the knowledge , skills , and attitudes of 2nd-year medical students regarding culturally competent healthcare , both in general and specific to Arab American Muslim patients . Method Participants ( N=199 ) , were 2nd-year Michigan State University College of Osteopathic Medicine students enrolled in a behavioral medicine course that included instruction on culturally competent healthcare . Students were r and omly assigned to a control ( N=102 ) or an experimental group ( N=97 ) . The experimental group was directed to an online , interactive patient simulation that featured an Arab American Muslim patient , and both groups completed a modified Clinical Cultural Competence Question naire to assess their knowledge , skills , and attitudes about culturally competent healthcare in general and specific to Arab American Muslim patients . Results There were knowledge and skills differences on two outcome measures for Arab American Muslim cultural competence measures in the experimental group . Across all of the measures , bilingual participants scored higher than English-speaking — only participants . Conclusion Preliminary data support the hypothesis that an online , interactive patient simulation involving the care of an Arab American Muslim patient has the potential to improve the knowledge and skills of 2nd-year medical students regarding the care of Arab American Muslim patients beyond the basic cultural-competence curriculum Introduction Effective strategies for teaching communication skills to health professions students are needed . This article describes the design and evaluation of immersive and interactive video simulations for medical students to practice basic communication skills . Methods Three simulations were developed , focusing on patient-centered interviewing techniques such as using open-ended questions , reflections , and empathic responses while assessing a patient 's history of present illness . First-year medical students were r and omized to simulation or education-as-usual arms . Students in the simulation arm were given access to three interactive video simulations developed using Articulate Storyline , an e-learning authoring tool , to practice and receive feedback on patient-centered interviewing techniques to prepare for their Observed Structured Clinical Examination ( OSCE ) . Trained raters evaluated videos of two OSCE cases for each participant to assess specific communication skills used during the history of present illness component of the interview . Results Eighty-seven percent of the students in the simulation arm interacted with at least one simulation during the history of present illness . For both OSCE cases , students in the simulation arm asked significantly more open-ended questions . Students in the simulation arm asked significantly fewer closed-ended questions and offered significantly more empathic responses in one OSCE case . No differences were found for reflections . Students reported that the simulations helped improve their communication skills . Conclusion The use of interactive video simulations was found to be feasible to incorporate into the curriculum and was appealing to students . In addition , students in the simulation arm displayed more behaviors consistent with the patient-centered interviewing model practice d in the simulations . Continued development and research are warranted INTRODUCTION To compare online learning tools , looped , branch serious game ( SG ) and linear text-based scenario ( TBS ) , among a sample of Belgian and Swiss pharmacy students . METHODS Open r and omized controlled study . The lesson was based on the case of a benign cough in a healthy child . A r and omized sample of 117 students : only the Swiss students had attended a previous lecture on coughs . Participation rate , pre- and post-experience Likert scales and students ' clinical knowledge were measured . RESULTS Our primary hypothesis was demonstrated : students favored the SG even if navigation was rated as more complex , and students who performed the SG better understood the aim of pharmacist triage in case of cough . The influence of the SG appeared to be linked to the presence of a previous lecture in the curriculum . DISCUSSION AND CONCLUSION SG and TBS are effective to teach pharmacist triage . Higher SG complexity should be used to teach the aim of pharmacist triage in the case of a specific disease and could be an alternative to simulated patients . A simpler TBS does not require a previous lecture and a debriefing to be fully effective Objective . To evaluate the efficacy of faculty-led problem-based learning ( PBL ) vs online simulated-patient case in fourth-year ( P4 ) pharmacy students . Design . Fourth-year pharmacy students were r and omly assigned to participate in either online branched-case learning using a virtual simulation platform or a small-group discussion . Preexperience and postexperience student assessment s and a survey instrument were completed . Evaluation . While there were no significant differences in the preexperience test scores between the groups , there was a significant increase in scores in both the virtual-patient group and the PBL group between the preexperience and postexperience tests . The PBL group had higher postexperience test scores ( 74.8±11.7 ) than did the virtual-patient group ( 66.5±13.6 ) ( p=0.001 ) . Conclusion . The PBL method demonstrated significantly greater improvement in postexperience test scores than did the virtual-patient method . Both were successful learning methods , suggesting that a diverse approach to simulated patient cases may reach more student learning styles Purpose To explore students ’ perceptions of virtual patient use in the clinical clerkship and develop a framework to evaluate effects of different integration strategies on students ’ satisfaction and perceptions of learning effectiveness with this innovation . Method A prospect i ve , multiinstitutional study was conducted at six schools ’ pediatric clerkships to assess the impact of integrating Web-based virtual patient cases on students ’ perceptions of their learning during 2004–2005 and 2005–2006 . Integration strategies were design ed to meet the needs of each school , and integration was scored for components of virtual patient use and elimination of other teaching method ologies . A student survey was developed , vali date d , and administered at the end of the clerkship to 611 students . Data were analyzed using confirmatory factor analysis and structural equation modeling . Results A total of 545 students ( 89 % ) completed the survey . Overall student satisfaction with the virtual patients was high ; students reported that they were more effective than traditional methods . The structural model demonstrated that elimination of other teaching method ologies was directly associated with perceived effectiveness of the integration strategies . A higher use score had a significant negative effect on perceived integration , but a positive effect on perceived knowledge and skills gain . Students ’ positive perceptions of integration directly affected their satisfaction and perception of the effectiveness of their learning . Conclusions Integration strategies balancing the use of virtual patients with elimination of some other requirements were significantly associated with students ’ satisfaction and their perceptions of improved knowledge and skills PURPOSE This study aim ed to compare the effects of computer-assisted , text-based and computer- and -text learning conditions on the performances of 3 groups of medical students in the pre- clinical years of their programme , taking into account their academic achievement to date . A fourth group of students served as a control ( no- study ) group . METHOD Participants were recruited from the pre- clinical years of the training programmes in 2 medical schools in Japan , Jichi Medical School near Tokyo and Kochi Medical School near Osaka . Participants were r and omly assigned to 4 learning conditions and tested before and after the study on their knowledge of and skill in performing an abdominal examination , in a multiple-choice test and an objective structured clinical examination ( OSCE ) , respectively . Information about performance in the programme was collected from school records and students were classified as average , good or excellent . Student and faculty evaluations of their experience in the study were explored by means of a short evaluation survey . RESULTS Compared to the control group , all 3 study groups exhibited significant gains in performance on knowledge and performance measures . For the knowledge measure , the gains of the computer-assisted and computer-assisted plus text-based learning groups were significantly greater than the gains of the text-based learning group . The performances of the 3 groups did not differ on the OSCE measure . Analyses of gains by performance level revealed that high achieving students ' learning was independent of study method . Lower achieving students performed better after using computer-based learning methods . CONCLUSION The results suggest that computer-assisted learning methods will be of greater help to students who do not find the traditional methods effective . Explorations of the factors behind this are a matter for future research OBJECTIVES To explore the values and assumptions underlying problem-based learning ( PBL ) cases through narrative analysis , in order to consider the ways by which paper cases may affect student attitudes and values . METHODS R and omly chosen PBL cases from the first year curriculum at Dalhousie University medical school ( n = 10 ) were coded by 3 independent review ers attending to narrative components . RESULTS The cases generally used spare , objective language , used the passive voice , eliminated agency , and employed linguistic markers to encode scepticism about patient reports . There was almost no sense of the presence of the patient as person in these cases in terms of their words , feelings , or their social and cultural context . The almost complete exclusion of the preferences and priorities of the patient was striking . CONCLUSION The sample is small , the results only suggestive . Yet it appears that the cases used in PBL may unnecessarily , even unintentionally , encourage student detachment from the messiness of real patients ' lives and emotions . Positioning a particular way of seeing - the doctor 's gaze - as normative renders less visible the choices that are being made whenever an account is constructed . Including multiple voices in a case would complicate that tidy reduction of choices . Ongoing attempts to enrich the case format should be encouraged . At the same time , students may benefit from being taught the skills for critical analysis of the case itself BACKGROUND Mannequin and computer-based simulators are useful for the practice of patient management , physical procedures , and competency . However , they are ineffective in teaching clinical medicine . StepStone Interactive Medical Software ( SS ) is a web-based medical learning modality that provides the user with a highly focused set of evaluative and interventional tasks to treat memorable virtual patients in a visual case-based format . OBJECTIVE To determine whether the SS learning modality is superior to traditional lecture format in medical student learning and retention . METHODS After Institutional Review Board ( IRB ) approval was obtained and the consents were signed , 30 third-year medical students were assigned r and omly to 2 groups of 15 students each : The control group received two 30-minute PowerPoint lectures ( Microsoft Corporation , Redmond , Washington ) about torsades de pointes ( TdP ) and pulseless electrical activity ( PEA ) , and the SS group was given 1 hour to review 2 SS cases teaching TdP and PEA . A preintervention test was given to assess their baseline knowledge . An immediate postintervention test was given to both groups . Twenty-two days later , a long-term retention test was administered . The results were analyzed using a Student t test for continuous variables . RESULTS The mean scores for the preintervention test in the control and SS groups were 44.9 ± 3 % and 44.1 ± 2 % , respectively ( p = 0.41 ) . The mean scores for the postintervention test in the control and SS groups were 61.7 ± 2 % and 86.7 ± 2 % , respectively ( p < 0.001 ) . Improvement from baseline knowledge was calculated , and the mean improvement was 16.8 ± 3 % in the control group and 42.5 ± 2 % in the SS group ( p < 0.001 ) . The long-term retention test revealed the mean scores of 55.8 ± 3 % in the control group and 70.1 ± 3 % in the SS group ( p < 0.001 ) . Long-term improvement from baseline knowledge was calculated and the control group improved by 10.9 ± 4 % , whereas the SS group improved by 26 ± 3 % ( p = 0.002 ) . CONCLUSIONS The SS learning modality demonstrated a significant improvement in student learning retention compared to traditional didactic lecture format . SS is an effective web-based medical education tool Computer-based clinical simulations for medical education vary widely in structure and for mat , yet few studies have examined which formats are optimal for particular educational setting s. This study is a r and omized comparison of the same simulated case in three formats : a " pedagogic " format offering explicit educational support , a " high-fidelity " format attempting to model clinical reasoning in the real world , and a " problem-solving " format that requires students to express specific diagnostic hypotheses Data were collected from rising third- year medical students using a posttest , attitudinal question naire , students ' writeups of the case , and log files of students ' progress through the simulation . Student performances on all measures differed significantly by format . In general , students using the pedagogic format were more proficient but less efficient . They acquired more information but were able to do proportionately less with it . The results suggest that the format of computer-based simulations is an important educational variable . Key words . medical education , undergraduate ; clinical reasoning ; computer-assisted instruction . ( Med Decis Making 1991;11:265 - 272 We have developed a computer assisted learning package for teaching clinical medical students about familial breast cancer . It explains the principles of genetic predisposition to breast cancer , the association with other cancers , the principles of family history taking and confirmation , risk assessment and possible interventions . Clinical medical students were r and omised to either conventional teaching or CAL , 48 students attended the evaluation session . Students r and omised to conventional teaching received a 20 min mini-lecture , those r and omised to CAL completed the package with technical , but not academic support available . At the end of the intervention both groups of students completed a short written assessment of acceptability and knowledge and underst and ing of breast cancer genetics . There was no significant difference between the CAL and mini-lecture groups in terms of marks or acceptability . Thus CAL appears to be an acceptable and effective method of teaching clinical medical students about familial breast cancer . Although time consuming to develop , CAL can be used in a variety of setting s to increase curriculum flexibility . Methods of motivating students to complete the CAL , and of providing educational support are being explored OBJECTIVE To determine the effect of computer-based medical teaching ( CBMT ) as a supplementary method to teach clinical problem-solving during the clerkship in neurology . DESIGN R and omized controlled blinded study . SETTING Academic Medical Centre , Amsterdam , the Netherl and s. METHOD 103 Students were assigned at r and om to a group with access to CBMT and a control group . CBMT consisted of 20 computer-simulated patients with neurological diseases , and was permanently available during five weeks to students in the CBMT group . The ability to recognize and solve neurological problems was assessed with two free-response tests , scored by two blinded observers . RESULTS The CBMT students scored significantly better on the test related to the CBMT cases ( mean score 7.5 on a zero to 10 point scale ; control group 6.2 ; p < 0.001 ) . There was no significant difference on the control test not related to the problems practised with CBMT . CONCLUSION CBMT can be an effective method for teaching clinical problem-solving , when used as a supplementary teaching facility during a clinical clerkship . The increased ability to solve problems learned by CBMT had no demonstrable effect on the performance with other neurological problems BACKGROUND We aim ed to determine if an immersive virtual patient ( VP ) with a breast complaint and a breast mannequin could prepare third-year medical students for history-taking ( HT ) and clinical breast examination ( CBE ) on a real patient . METHODS After st and ardized instruction in breast HT and CBE , students ( n = 21 ) were r and omized to either an interaction with a VP ( experimental ) or to no VP interaction ( control ) before seeing a real patient with a breast complaint . Participants completed baseline and exit surveys to assess confidence regarding their HT and CBE skills . RESULTS Students reported greater confidence in their HT ( Delta value = 1.05 + /- 1.28 , P < .05 ) and CBE skills ( Delta value = 1.14 + /- .91 , P < .05 ) and less anxiety when performing a CBE ( Delta value = -.76 + /- 1.10 , P < .05 ) . The VP intervention group had a significantly higher mean HT confidence than the control group at the conclusion of the study ( 4.27 + /- .47 vs 3.50 + /- .71 , respectively , P < .05 ) . CONCLUSIONS A single interaction with a VP with a breast complaint and breast mannequin improves student confidence in breast HT during a surgery clerkship Purpose To compare the educational effectiveness of two virtual patient (VP)-based e-learning strategies , versus no training , in improving physicians ’ substance abuse management knowledge , attitudes , self-reported behaviors , and decision making . Method The 2011–2012 study was a posttest-only , three-arm , r and omized controlled trial in 90 resident and 30 faculty physicians from five adult medicine primary care training programs . The intervention was one of two 2-hour VP-based e-learning programs , design ed by national experts to teach structured screening , brief interventions , referral , and treatment skills . One used traditional problem solving with feedback ( unworked example ) , and the other incorporated an expert demonstration first , followed by problem solving with feedback ( worked example ) . The main outcome measure was performance on the Physicians ’ Competence in Substance Abuse Test ( P-CSAT , maximum score = 315 ) , a self-administered , previously vali date d measure of physicians ’ competence in managing substance abuse . The survey was completed at the outset of the study and two months later . Results Overall P-CSAT scores were virtually identical ( 202–211 , P > .05 ) between both intervention groups and the no-training control group at both times . Average faculty P-CSAT scores ( 221.9 , 224.6 ) were significantly higher ( P < .01 ) than resident scores ( 203.7 , 202.5 ) at both times . Conclusions This study did not provide evidence that a brief , worked example , VP-based e-learning program or a traditional , unworked , VP-based e-learning program was superior to no training in improving physicians ’ substance abuse management skills . The study did provide additional evidence that the P-CSAT distinguishes between physicians who should possess different levels of substance abuse management skills Background : Previous investigations have established the need for improved training for management of anesthetic emergencies . Training with inexpensive screen-based anesthesia simulators may prove to be helpful . Purpose s : We measured the effectiveness of screen-based simulator training with debriefing on the response to simulated anesthetic critical incidents . Methods : Thirty-one 1st-year clinical anesthesia residents were r and omized into 2 groups . The intervention group h and led 10 anesthetic emergencies using the screen-based anesthesia simulator program and received written feedback on their management , whereas the traditional ( control ) group was asked to study a h and out covering the same 10 emergencies . All residents then were evaluated on their management of 4 st and ardized scenarios in a mannequin-based simulator using a quantitative scoring system . Results : The average point score for the simulator-with-debriefing group was 52.6 + /- 9.9 out of 95 possible points . The traditional group average point score was 43.4 + /- 5.9 , p = . 004 . Conclusions : Residents who managed anesthetic problems using a screen-based anesthesia simulator h and led the emergencies in a mannequin-based anesthesia simulator better than residents who were asked to study a h and out covering the same problems . Computer simulations with feedback are effective as a supplement to traditional residency training methods for the management of medical emergencies The purpose of this study was to assess the efficacy and efficiency of CAI for students learning evaluation and treatment skills for carpal tunnel syndrome ( CTS ) . Ten volunteer physical therapy students were r and omly assigned into either CAI or interactive lecture instructional groups . Each student completed a 36-item pretest on CTS . The CAI group used the Physical Therapy Patient Simulator CAI and the instructional group participated in lecture/ discussion to complete the case studies . Following completion of instruction , an identical 36 item posttest was administered to all students . Individual start and finish times for the two groups were recorded by the instructor . A 2 x 2 ANOVA revealed no significant difference in pretest/posttest scores between CAI and interactive lecture . A t-test determined the CAI group completed the case assignment 30 minutes ( 24 % faster than the interactive group . The findings suggest that using a CAI simulation program may be as effective and more efficient than traditional methods of instruction BACKGROUND Computer-based teaching may allow effective teaching of important psychiatric knowledge and skills . AIMS To investigate the effectiveness and acceptability of computer-based teaching . METHOD A single-blind , r and omized , controlled study of 166 undergraduate medical students at the University of Leeds , involving an educational intervention of either a structured lecture or a computer-based teaching package ( both of equal duration ) . RESULTS There was no difference in knowledge between the groups at baseline or immediately after teaching . Both groups made significant gains in knowledge after teaching . Students who attended the lecture rated their subjective knowledge and skills at a statistically significantly higher level than students who had used the computers . Students who had used the computer package scored higher on an objective measure of assessment skills . Students did not perceive the computer package to be as useful as the traditional lecture format , despite finding it easy to use and recommending its use to other students . CONCLUSIONS Medical students rate themselves subjectively as learning less from computer-based as compared with lecture-based teaching . Objective measures suggest equivalence in knowledge acquisition and significantly greater skills acquisition for computer-based teaching Objectives : To determine the feasibility and effectiveness of virtual-patient computer-assisted instruction ( CAI ) in pre-clerkship undergraduate otolaryngology education . Study Design : Prospect i ve , r and omized , controlled trial . Subjects and Methods : Second-year medical students at the University of Western Ontario , Canada , were r and omized into two groups : group A was given a CAI module and group B was presented with two Internet review articles , both covered specific learning objectives for pediatric stridor . Students completed r and omized pre- and post-tests and a question naire one week later . Results : Fifty-five students completed the study with 28 in group A and 27 in group B. Mean pretest scores were 59.1 % in group A and 59.8 % in group B ( 95 % CI = −7.9 % to 10.4 % ) . Mean post-test scores were significantly elevated in group A ( 84.6 % , P < 0.001 ) and group B ( 74.3 % , P = 0.008 ) . Group A had a significantly higher ( P = 0.02 ) mean post-test score than group B ( mean difference of 10.2 % ) . Students spent significantly more time ( P < 0.001 ) reading text articles ( 25.5 minutes ) than completing the CAI ( 9.06 minutes ) . Forty-one ( 66 % ) students completed the survey . Thirty-six ( 88 % ) respondents indicated that they preferred CAI to online articles . Conclusion : CAI is a feasible , effective , and efficient means of enhancing self-directed learning as supplementation to the pre-clerkship undergraduate otolaryngology curriculum Optimizing the usability of e-learning material s is necessary to reduce extraneous cognitive load and maximize their potential educational impact . However , this is often neglected , especially when time and other re sources are limited . We conducted a r and omized trial to investigate whether a usability evaluation of our multimedia e-learning re source , followed by fixing of all problems identified , would translate into improvements in usability parameters and learning by medical residents . Two iterations of our e-learning re source [ version 1 ( V1 ) and version 2 ( V2 ) ] were compared . V1 was the first fully functional version and V2 was the revised version after all identified usability problems were addressed . Residents in internal medicine and anesthesiology were r and omly assigned to one of the versions . Usability was evaluated by having participants complete a user satisfaction question naire and by recording and analyzing their interactions with the application . The effect on learning was assessed by questions design ed to test the retention and transfer of knowledge . Participants reported high levels of satisfaction with both versions , with good ratings on the System Usability Scale and adjective rating scale . In contrast , analysis of video recordings revealed significant differences in the occurrence of serious usability problems between the two versions , in particular in the interactive H and sOn case with its treatment simulation , where there was a median of five serious problem instances ( range : 0 - 50 ) recorded per participant for V1 and zero instances ( range : 0 - 1 ) for V2 ( P < 0.001 ) . There were no differences in tests of retention or transfer of knowledge between the two versions . In conclusion , usability evaluation followed by a re design of our e-learning re source result ed in significant improvements in usability . This is likely to translate into improved motivation and willingness to engage with the learning material . In this population of relatively high-knowledge participants , learning scores were similar across the two versions CONTEXT Diagnostic efficiency is important in daily clinical practice as doctors have to face problems within a limited time frame . To foster the clinical reasoning of students is a major challenge in medical education research . Little is known about students ' diagnostic efficiency . On the basis of current theories , scaffolds for case representation ( statement of the case as far as it is summarised in the mind ) could be a promising approach to make the diagnostic reasoning of intermediate medical students more efficient . METHODS Clinical case processing of 88 medical students in their fourth and fifth years was analysed in a r and omised , controlled laboratory study . Cases dealing with dyspnoea were provided in an electronic learning environment ( CASUS ) . Students could freely choose the time , amount and sequence of clinical information . During the learning phase the intervention group was asked to write down case representation summaries while working on the cases . In the assessment phase diagnostic efficiency was operationalised as the number of correct diagnoses divided by the time spent on diagnosing . RESULTS Diagnostic efficiency was significantly improved by the representation scaffolding ( M = 0.12 [ SD = 0.07 ] , M = 0.09 [ SD = 0.06 ] correct cases/time , p = 0.045 ) , whereas accuracy remained unchanged ( M = 2.28 [ SD = 1.10 ] , M = 2.09 [ SD = 1.08 ] , p = 0.52 ) . Both groups screened the same amount of clinical information , but the scaffolding group did this faster ( M = 20.8 minutes [ SD = 7.15 ] , M = 24.6 minutes [ SD = 7.42 ] , p = 0.01 ; Cohen 's d = 0.5 ) . CONCLUSION Diagnostic efficiency is an important outcome variable in clinical reasoning research as it corresponds to workplace challenges . Scaffolding for case representations significantly improved the diagnostic efficiency of fourth and fifth-year medical students , most likely because of a more targeted screening of the available information AIMS Two types of virtual patient design s can be distinguished : a ' narrative ' structure and a ' problem-solving ' structure . This study compares the same virtual patient with two different structures within the domain of communication skills . METHODS Two virtual patients were constructed around the same case , one emphasizing a narrative and one a problem-solving model . Use of these packages was trialled with undergraduate medical students over 2 years . Students were r and omly assigned to tutorials using the virtual patients , and their communication skills were compared with baseline performance by a separate group . Outcome was assessed by evaluation of an interview with a simulated patient . RESULTS There was no significant difference between the three groups in overall communication skills . However there was a significant improvement in the communication skills of the narrative group when compared only with the problem-solving group . Additionally , various aspects of communication skills , such as use of open-ended questions and appropriate language , showed significant differences between the three groups . CONCLUSION There is some evidence to support the value of a narrative design for virtual patients which are to be used to teach communication skills , which encourages further investigation AIMS AND OBJECTIVES To provide evidence on the effectiveness of simulation activities on the clinical decision-making abilities of undergraduate nursing students . Based on previous research , it was hypothesised that the higher the cognitive score , the greater the ability a nursing student would have to make informed valid decisions in their clinical practice . BACKGROUND Globally , simulation is being espoused as an education method that increases the competence of health professionals . At present , there is very little evidence to support current investment in time and re sources . METHODS Following ethical approval , fifty-eight third-year undergraduate nursing students were r and omised in a pretest-post-test group-parallel controlled trial . The learning environment preferences ( LEP ) inventory was used to test cognitive abilities in order to refute the null hypothesis that activities in computer-based simulated learning environments have a negative effect on cognitive abilities when compared with activities in skills laboratory simulated learning environments . RESULTS There was no significant difference in cognitive development following two cycles of simulation activities . Therefore , it is reasonable to assume that two simulation tasks , either computer-based or laboratory-based , have no effect on an undergraduate student 's ability to make clinical decisions in practice . However , there was a significant finding for non-English first- language students , which requires further investigation . CONCLUSIONS More longitudinal studies that quantify the education effects of simulation on the cognitive , affective and psychomotor attributes of health science students and professionals from both English-speaking and non-English-speaking background s are urgently required . It is also recommended that to achieve increased participant numbers and prevent non-participation owing to absenteeism , further studies need to be imbedded directly into curricula . RELEVANCE TO CLINICAL PRACTICE This investigation confirms the effect of simulation activities on real-life clinical practice , and the comparative learning benefits with traditional clinical practice and university education remain unknown Abstract BACKGROUND : We developed computer-based virtual patient ( VP ) cases to complement an interactive continuing medical education ( CME ) course that emphasizes skills practice using st and ardized patients ( SP ) . Virtual patient simulations have the significant advantages of requiring fewer personnel and re sources , being accessible at any time , and being highly st and ardized . Little is known about the educational effectiveness of these new re sources . We conducted a r and omized trial to assess the educational effectiveness of VPs and SPs in teaching clinical skills . OBJECTIVE : To determine the effectiveness of VP cases when compared with live SP cases in improving clinical skills and knowledge . DESIGN : R and omized trial . PARTICIPANTS : Fifty-five health care providers ( registered nurses 45 % , physicians 15 % , other provider types 40 % ) who attended a CME program . INTERVENTIONS : Participants were r and omized to receive either 4 live cases ( n=32 ) or 2 live and 2 virtual cases ( n=23 ) . Other aspects of the course were identical for both groups . RESULTS : Participants in both groups were equivalent with respect to pre-post workshop improvement in comfort level ( P=.66 ) and preparedness to respond ( P=.61 ) , to screen ( P=.79 ) , and to care ( P=.055 ) for patients using the skills taught . There was no difference in subjective ratings of effectiveness of the VPs and SPs by participants who experienced both ( P=.79 ) . Improvement in diagnostic abilities were equivalent in groups who experienced cases either live or virtually . CONCLUSIONS : Improvements in performance and diagnostic ability were equivalent between the groups and participants rated VP and SP cases equally . Including well- design ed VPs has a potentially powerful and efficient place in clinical skills training for practicing health care workers BACKGROUND Teaching using paper problem-based learning ( p-PBL ) sessions has left some students fatigued with the learning process . Therefore , attempts have been made to replace p-PBL with digitally enhanced , decision-making PBL in the form of virtual patients ( VP ) . Student enthusiasm for substituting p-PBL with VP has not been quantitatively evaluated on the intended educational effects . AIM To determine the educational effects of substituting p-PBL sessions with VP on undergraduate medical students in their internal medicine course . METHODS We conducted a r and omised controlled study on 34 third-year undergraduate medical students in the academic year 2015 - 2016 . Student performance after an intervention substituting p-PBL sessions with VP was analysed . The educational outcomes were measured with knowledge exams and the Diagnostic Thinking Inventory . RESULTS There was no difference in exam performance between groups ( P > 0.833 ) immediately after the intervention , or in long term . Nor was there a significant difference in improvement of diagnostic thinking between groups ( P > 0.935 and P > 0.320 ) . CONCLUSIONS Our study showed no significant improvement in diagnostic thinking abilities or knowledge exam results with the use of VP . Educators can add VP to sessions to motivate students , but a significant improvement to educational outcome should not be expected Simulations are important educational tools in the development of health care competence . This study describes a virtual learning environment ( VLE ) for diagnosis and treatment planning in oral health care . The VLE is a web-based , data base application where the learner uses free text communication on the screen to interact with patient data . The VLE contains forms for history taking , clinical images , clinical data and X-rays . After review ing the patient information , the student proposes therapy and makes prognostic evaluations of the case in free text . A usability test of the application was performed with seven dental students . The usability test showed that the software responded with correct answers to the majority of the free text questions . The application is generic in its basic functions and can be adapted to other dental or medical subject areas . A r and omised controlled trial was carried out with 39 students who attended instruction in history taking with problem-based learning cases , lectures and seminars . In addition , 16 of the 39 students were r and omly chosen to practise history taking using the virtual patient prior to their first patient encounter . The performance of each student was recorded on video during the patient sessions . The type and order of the questions asked by the student and the degree of empathy displayed towards the patient were analysed systematic ally on the videos . The data indicate that students who also undertook history taking with a virtual patient asked more relevant questions , spent more time on patient issues , and performed a more complete history interview compared with students who had only undergone st and ard teaching . The students who had worked with the virtual patient also seemed to have more empathy for the patients than the students who had not . The practising of history taking with a virtual patient appears to improve the capability of dental students to take a relevant oral health history CONTEXT Computer-assisted learning ( CAL ) in medical education has been shown to be effective in the achievement of learning outcomes , but requires the input of significant re sources and development time . This study examines the key elements and processes that led to the widespread adoption of a CAL program in undergraduate medical education , the Computer-assisted Learning in Paediatrics Program ( CLIPP ) . It then considers the relative importance of elements drawn from existing theories and models for technology adoption and other studies on CAL in medical education to inform the future development , implementation and testing of CAL programs in medical education . METHODS The study used a mixed- methods explanatory design . All paediatric clerkship directors ( CDs ) using CLIPP were recruited to participate in a self-administered , online question naire . Semi-structured interviews were then conducted with a r and om sample of CDs to further explore the quantitative results . RESULTS Factors that facilitated adoption included CLIPP 's ability to fill gaps in exposure to core clinical problems , the use of a national curriculum , development by CDs , and the meeting of CDs ' desires to improve teaching and student learning . An additional facilitating factor was that little time and effort were needed to implement CLIPP within a clerkship . The quantitative findings were mostly corroborated by the qualitative findings . CONCLUSIONS This study indicates issues that are important in the consideration and future exploration of the development and implementation of CAL programs in medical education . The promise of CAL as a method of enhancing the process and outcomes of medical education , and its cost , increase the need for future CAL funders and developers to pay equal attention to the needs of potential adopters and the development process as they do to the content and tools in the CAL program . Important questions that remain on the optimal design , use and integration of CAL should be addressed in order to adequately inform future development . Support is needed for studies that address these critical areas Introduction The purpose s of this study were to ( 1 ) compare learning outcomes between students who participated in mannequin-based simulation activities and students who participated in virtual simulation activities and ( 2 ) describe a cost-utility analysis comparing the two types of simulation activities in terms of costs and multiple measures of effectiveness . Methods Nursing student participants were r and omly assigned to one of two experimental groups to complete either a mannequin-based or virtual simulation activity . The simulation scenario was the same for both groups and involved the care of a hospitalized patient experiencing a chronic obstructive pulmonary disease exacerbation . Participants completed presimulation and postsimulation assessment s reflecting qualitative and quantitative measures of learning . A r and om sample of participants from each group completed a postsimulation performance assessment during which they interacted one on one with a st and ardized patient . Results Eighty-four nursing students were enrolled in the study and completed the simulation activities . There were no significant differences in quantitative measures of learning or performance between participants in the mannequin-based and virtual simulation groups . Participants ’ qualitative responses to postintervention written reflections and questions yielded additional data for describing learning from the two interventions . In the cost-utility analysis , the virtual simulation activity had a more favorable cost-utility ratio of US $ 1.08 versus the mannequin-based simulation activity ’s US $ 3.62 . Conclusions Healthcare educators striving to make evidence -based decisions about how to best employ simulation pedagogy may consider these findings about the cost utility of various simulation modalities . However , additional research is needed Synthesizing evidence from r and omized controlled trials of digital health education poses some challenges . These include a lack of clear categorization of digital health education in the literature ; constantly evolving concepts , pedagogies , or theories ; and a multitude of methods , features , technologies , or delivery setting s. The Digital Health Education Collaboration was established to evaluate the evidence on digital education in health professions ; inform policymakers , educators , and students ; and ultimately , change the way in which these professionals learn and are taught . The aim of this paper is to present the overarching methodology that we use to synthesize evidence across our digital health education review s and to discuss challenges related to the process . For our research , we followed Cochrane recommendations for the conduct of systematic review s ; all review s are reported according to the PRISMA ( Preferred Reporting Items for Systematic Review s and Meta-Analyses ) guidance . This included assembling experts in various digital health education fields ; identifying gaps in the evidence base ; formulating focused research questions , aims , and outcome measures ; choosing appropriate search terms and data bases ; defining inclusion and exclusion criteria ; running the search es jointly with librarians and information specialists ; managing abstract s ; retrieving full-text versions of papers ; extracting and storing large data sets , critically appraising the quality of studies ; analyzing data ; discussing findings ; drawing meaningful conclusions ; and drafting research papers . The approach used for synthesizing evidence from digital health education trials is commonly regarded as the most rigorous benchmark for conducting systematic review s. Although we acknowledge the presence of certain biases ingrained in the process , we have clearly highlighted and minimized those biases by strictly adhering to scientific rigor , method ological integrity , and st and ard operating procedures . This paper will be a valuable asset for research ers and method ologists undertaking systematic review s in digital health education Background : The precise effect and the quality of different cases used in dermatology problem-based learning ( PBL ) curricula are yet unclear . Aim : To prospect ively compare the impact of real patients , digital , paper PBL ( PPBL ) and traditional lecture-based learning ( LBL ) on academic results and student perceptions . Methods : A total of 120 students were r and omly allocated into either real- patients PBL ( RPBL ) group studied via real-patient cases , digital PBL ( DPBL ) group studied via digital-form cases , PPBL group studied via paper-form cases , or conventional group who received didactic lectures . Academic results were assessed through review of written examination , objective structured clinical examination and student performance scores . A five-point Likert scale question naire was used to evaluate student perceptions . Results : Compared to those receiving lectures only , all PBL participants had better results for written examination , clinical examination and overall performance . Students in RPBL group exhibited better overall performance than those in the other two PBL groups . Real-patient cases were more effective in helping develop students ’ self-directed learning skills , improving their confidence in future patient encounters and encouraging them to learn more about the discussed condition , compared to digital and paper cases . Conclusion : Both real patient and digital triggers are helpful in improving students ’ clinical problem-h and ling skills . However , real patients provide greater benefits to students Objective There is increasing use of educational technologies in medical and surgical specialties . Described herein is the development and application of an interactive virtual patient ( VP ) to teach suicide risk assessment to health profession trainees . We studied the effect of the following : ( 1 ) an interaction with a bipolar VP who attempts suicide or ( 2 ) completion of a video-teaching module on interviewing a bipolar patient , on medical students ’ proficiency in assessing suicide risk in st and ardized patients . We hypothesized that students who interact with a bipolar VP will be at least as likely to assess suicide risk , as their peers who completed a video module . Methods In a r and omized , controlled study , we compared the frequency with which second-year students at the Medical College of Georgia asked suicide risk and bipolar symptoms questions by VP/video group . Results We recruited 67 students . The VP group inquired more frequently than the video group in 4 of 5 suicide risk areas and 11 of 14 other bipolar symptomatology areas . There were minimal to small effect sizes in favor of the VP technology . The students preferred the video over the VP as an educational tool ( p = 0.007 ) . Conclusions Our study provides proof of concept that both VP and video module approaches are feasible for teaching students to assess suicide risk , and we present evidence about the role of active learning to improve communication skills . Depending on the learning context , interviewing a VP or observation of a videotaped interview can enhance the students ’ suicide risk assessment proficiency in an interview with a st and ardized patient . An interactive VP is a plausible modality to deliver basic concepts of suicide risk assessment to medical students , can facilitate individual preferences by providing easy access and portability , and has potential generalizability to other aspects of psychiatric training |
726 | 29,192,423 | There was insufficient evidence to confirm or exclude differences in adverse effects of bisphosphonates ( RR 1.05 , 95 % CI 0.95 to 1.76 ; 2 studies , 437 participants ; low- quality evidence ) and treatment discontinuation ( 2 studies , 437 participants ) ( RR 2.04 , 95 % CI 0.43 to 9.59 ; 2 studies , 437 participants ; very low- quality evidence ) .Intensive versus symptomatic treatmentThere was no consistent evidence of difference to response in bone pain , bodily pain or quality of life in participants who received intensive versus symptomatic treatment .
We found moderate- quality evidence that bisphosphonates improved pain in people with Paget 's disease of bone when compared with placebo .
We found insufficient evidence of benefit in terms of pain or quality of life from intensive treatment . | BACKGROUND Bisphosphonates are considered to be the treatment of choice for people with Paget 's disease of bone .
However , the effects of bisphosphonates on patient-centred outcomes have not been extensively studied .
There are insufficient data to determine whether reducing and maintaining biochemical markers of bone turnover to within the normal range improves quality of life and reduces the risk of complications .
OBJECTIVES To assess the benefits and harms of bisphosphonates for adult patients with Paget 's disease of bone . | BACKGROUND The advent of bisphosphonates advanced therapy for Paget 's disease , but more effective and convenient agents are needed to increase adherence . Zoledronic acid , a bisphosphonate administered as a single intravenous infusion , might meet these needs . METHODS In two identical , r and omized , double-blind , actively controlled trials of 6 months ' duration , we compared one 15-minute infusion of 5 mg of zoledronic acid with 60 days of oral risedronate ( 30 mg per day ) . The primary efficacy end point was the rate of therapeutic response at six months , defined as a normalization of alkaline phosphatase levels or a reduction of at least 75 percent in the total alkaline phosphatase excess . The results of the studies were pooled . RESULTS At six months , 96.0 percent of patients receiving zoledronic acid had a therapeutic response ( 169 of 176 ) , as compared with 74.3 percent of patients receiving risedronate ( 127 of 171 , P<0.001 ) . Alkaline phosphatase levels normalized in 88.6 percent of patients in the zoledronic acid group and 57.9 percent of patients in the risedronate group ( P<0.001 ) . Zoledronic acid was associated with a shorter median time to a first therapeutic response ( 64 vs. 89 days , P<0.001 ) . Higher response rates in the zoledronic acid group were consistent across all demographic , disease-severity , and treatment-history subgroups and with changes in other bone-turnover markers . The physical-component summary score of the Medical Outcomes Study 36-item Short-Form General Health Survey , a measure of the quality of life , increased significantly from baseline at both three and six months in the zoledronic acid group and differed significantly from those in the risedronate group at three months . Pain scores improved in both groups . During post-trial follow-up ( median , 190 days ) , 21 of 82 patients in the risedronate group had a loss of therapeutic response , as compared with 1 of 113 patients in the zoledronic acid group ( P<0.001 ) . CONCLUSIONS A single infusion of zoledronic acid produces more rapid , more complete , and more sustained responses in Paget 's disease than does daily treatment with risedronate Several Biophosphonates have been used as therapeutic agents for Paget 's bone disease . ( Chloro-4 phenyl)thiomethylene-bisphosphonate ( CIPsMBP ) has recently been shown to have significant antiosteoclastic activity while an affect of CIPsMBP on mineralization was only observed at high doses . We tested this drug for 6 months in 23 pagetic patients distributed in three groups . Gr 1 ( n = 5 ) receiving 200 mg/day showed a decrease of serum alkaline phosphatase ( SAP ) to 42 + /- 4 % ( p less than 0.01 ) of initial value ( 100 % ) while hydroxyprolinuria/creatinuria ratio ( OH/Cr ) dropped to 69 + /- 8 % of baseline . In 4 patients receiving 400 mg/day , SAP improved to 48 + /- 9 % of initial value ( p less than 0.01 ) and OH/Cr to 40 + /- 3 % ( p less than 0.01 ) . In the last group ( n = 14 ) receiving 200 mg/day for 3 months , and 400 mg/day thereafter up to the 6th month SAP decreased to 53 + /- 4 % and OH/Cr to 62 + /- 6 % of initial value ( p less than 0.01 ) . Clinical improvement was significant from the first month of treatment . No resistance ( mean decrease of SAP lower than 30 % ) was recorded and no radiological or clinical evidence of mineralization defect appeared . The clinical and biological tolerance was excellent throughout the study Summary Daily oral tablet bisphosphonate therapy for Paget ’s disease of bone may cause serious upper gastrointestinal adverse events . A once-weekly alendronate 280 mg oral buffered solution was compared with an alendronate 40 mg/day tablet . While both were similarly effective , the tablet appeared to be better tolerated in this study . Introduction Although daily doses of oral bisphosphonates are a generally safe and effective treatment for Paget ’s disease of bone ( PDB ) , some patients may experience upper gastrointestinal adverse events ( UGI AEs ) or find the dosing requirements inconvenient and become noncompliant . A once-weekly ( OW ) oral dose of bisphosphonate in buffered solution ( OBS ) may be as effective , better tolerated , and more convenient . Methods Sixty-three patients were r and omized to either alendronate ( ALN ) 280 mg OW OBS ( n = 42 ) or an ALN 40 mg/day tablet ( n = 21 ) during a 6-month , r and omized , double-blind , active-controlled trial . The primary endpoint was the mean percent decrease in total serum alkaline phosphatase ( total ALP ) from baseline at 6 months . Results There were no significant differences in total ALP between groups during the 6-month period . There was a higher incidence of clinical AEs in the ALN 280 mg OW OBS ( 79 % ) vs. the ALN 40 mg/day tablet group ( 67 % ) , including drug related AEs ( 48 % and 10 % , respectively ) , which led to study discontinuation ( 19.0 % and 10 % , respectively ) . Conclusions Although ALN 280 mg OW OBS was similarly effective as ALN 40 mg/day in reducing total ALP in patients with PDB , the ALN 40 mg/day tablet appears to be better tolerated than ALN 280 mg OW OBS Abstract The diphosphonate , sodium etidronate ( disodium ethane-1-hydroxy-1,1-diphosphonate ) ( E.H.D.P. ) , which inhibits the growth and dissolution of calcium phosphate crystals in vitro , was given at doses of 0 , 1 , 5 , 10 , or 20 mg . per kg . per day for up to 6 months to forty-seven patients with Paget 's disease of bone . There was a dose-related suppression of the raised alkaline phosphatase in plasma and total hydroxyproline in urine , and at 20 mg . per kg . per day nearly half of the patients had normal values at the end of treatment . A single course of E.H.D.P. could maintain biochemical remission for at least 2 years after stopping treatment . Bone biopsy specimens confirmed the suppression of the Paget 's disease . Increases in unmineralised osteoid were only seen in biopsy specimens taken after the higher doses of E.H.D.P. and were usually small . There was also a reversible rise in plasma-phosphate at 20 mg . per kg . per day . It is suggested that E.H.D.P. given for short periods could provide a simple and reliable oral therapy in those cases of Paget 's disease in which treatment is regarded as desirable Bisphosphonates are widely regarded as the treatment of choice for Paget 's disease of bone ( PDB ) because of their potent inhibitory effects on bone turnover , but the effects of bisphosphonate therapy on symptoms and complications of PDB have been little studied . Here we report the results of a r and omized trial that compared the effects of symptomatic treatment with intensive bisphosphonate therapy in a cohort of 1324 patients with PDB who were followed up for a median of 3 years ( range 2 to 5 years ) . The symptomatic treatment group was treated only if they had pagetic bone pain , for which they were first given analgesics or anti-inflammatory drugs , followed by bisphosphonates if they did not respond . The intensive group received repeat courses of bisphosphonates irrespective of symptoms with the aim of reducing and maintaining serum alkaline phosphatase ( ALP ) levels within the normal range . The endpoints were fracture , orthopedic surgery , quality of life , bone pain , and hearing thresholds . Serum ALP levels were significantly lower in the intensive treatment group than in with the symptomatic treatment group within 4 months of commencing treatment and remained lower throughout the study ( p < .001 ) . There was no difference between the groups in quality of life ( as assessed by the SF36 question naire ) , in overall bodily pain , or in pagetic bone pain . Hearing thresholds , as assessed by audiometry did not change significantly and did not differ between the treatment groups . Clinical fractures occurred in 46 of 661 patients ( 7.0 % ) in the intensive treatment group compared with 49 of 663 patients ( 7.4 % ) in the symptomatic treatment group , and orthopedic surgery was required in 50 of 661 patients ( 7.3 % ) in the intensive treatment group and in 55 of 663 patients ( 8.3 % ) in the symptomatic treatment group . These differences were not significant . Subgroup analyses of patients with elevated ALP levels at baseline and those who did or did not receive bisphosphonates during the study yielded similar results to those in the study group as a whole . We conclude that striving to maintain normal ALP levels with intensive bisphosphonate therapy confers no clinical advantage over symptom-driven management in patients with established PDB . Neither management strategy had a significant beneficial impact on pain or quality of life ( Clinical trial registration number IS RCT N12989577 ) Subjects ( 109 ) with symptomatic Paget 's disease of bone were treated with 5 , 10 , or 20 mg of sodium etidronate (EHDP)/kg body weight - day for 6 to 24 months . Significant decreases in serum alkaline phosphatase and urinary hydroxyproline were noted after 6 months of therapy ; no significant further improvement result ed after prolonged therapy . Some patients maintained biochemical remission after withdrawal of EHDP but others showed a relapse , related primarily to the pretreatment severity . Clinical improvement was noted in 61 % of the patients . Similar findings were seen after a second course of EHDP . No side-effects were noted in patients treated with 5 mg of EHDP/kg body weight - day . In patients treated with 10 or 20 mg of EHDP/kg body weight - day , severe diarrhea , bone pain , and nontraumatic fractures were noted in 3 , 13 , and 12 patients respectively . Quantitative histomorphometry showed mineralization delay in patients receiving 10 or 20 mg of EHDP/kg body weight - day but not in those receiving 5 mg/kg body weight - day . Five milligrams of EHDP/kg body weight - day was effective and appears to be safer than the higher doses The use of disodium ethane-1 hydroxy-1 , 1-diphosphonate ( EHDP ) therapy for Paget 's disease of bone was examined in 75 affected patients . Forty-eight patients received r and omly assigned oral doses of either 0 , 2.5 , 5 , 10 , or 20 mg/kg/day in a controlled , double-blind protocol , and the remainder received either 10 or 20 mg/kg/day in a non-r and om protocol . The clinical status of the patients and appropriate laboratory tests were evaluated before treatment and at frequent intervals during a six-month period of initial therapy . There were no significant changes in either urinary hydroxyproline or serum alkaline phosphatase in those patients receiving placebos , while both these parameters decreased significantly at all dose levels of EHDP , with the greatest decline noted in the highest dose group . However , statistical analysis of the data related to changes in symptoms in the double-blind study revealed that patients receiving the higher dose of EHDP ( 10 or 20 mg/kg/day ) had less favorable outcomes than those receiving the lower doses ( 2.5 or 5 mg/kg/day ) . The high does group had a relatively lower rate of symptom improvement and a relatively greater rate of deterioration than did the low dose group . Twenty-one of forty-nine patients followed for at least 18 months have shown a sustained suppression of their serum alkaline phosphatase and urinary hydroxyproline values for 12 months following cessation of EHDP , while therapy has been reinstituted for the other 28 patients because of increases in these measurements , with or without accompanying symptomatic deterioration . Eight patients sustained fractures through Pagetic bone during the period of study and all of these were treated with higher doses of EHDP . On the basis of the biochemical and clinical data in this study it appears that initial therapy of Paget 's disease of bone with 5 mg EHDP/kg/day maximizes benefits while minimizing possible adverse effects Paget ’s disease of bone is a relatively common condition of unknown aetiology characterized by an increase in bone turnover . Many forms of treatment have been advocated but at the present time only the calcitonins ( 2 , 4 , 7 ) and the diphosphonates ( 1 , 3 , 5 , 11 ) offer practical forms of specific therapy Alendronate , an aminobisphosphonate , is much more potent than etidronate , an older bisphosphonate , in inhibiting osteoclast-mediated bone resorption , and unlike etidronate , therapeutic doses of alendronate are not associated with abnormal mineralization . In the present study , we compared the effectiveness , safety , and tolerability of 6 months of daily oral administration of alendronate ( 40 mg ) with those of etidronate ( 400 mg ) in 89 patients with clinical ly active Paget 's disease . The primary efficacy end point was the percent change in serum alkaline phosphatase . Other end points included changes in urinary deoxypyridinoline excretion , pain , functional impairment scores , and radiological osteolysis . Tetracycline-labeled bone biopsies were obtained for histomorphometric analysis from a subset of 43 patients at the 6-month visit . The alendronate-treated group had significantly greater decreases in both serum alkaline phosphatase ( 79 % vs. 44 % ) and urinary deoxypyridinoline ( 75 % vs. 51 % ) than the etidronate-treated group ( P < 0.001 in both cases ) . Normalization of serum alkaline phosphatase was much more frequent in alendronate-treated patients ( 63.4 % vs. 17.0 % ; P < 0.001 ) . Alendronate was well tolerated and had a safety profile similar to that of etidronate . Histomorphometry revealed decreased bone turnover and no qualitative abnormalities , including no direct negative effects on bone mineralization , with alendronate treatment . One patient receiving etidronate developed frank osteomalacia . Alendronate appears to be a highly effective treatment for Paget 's disease of bone that offers an important therapeutic advance over etidronate UNLABELLED This r and omized study compared different intravenous bisphosphonates in PDB . Zoledronate was superior with respect to pamidronate in achieving biochemical remission , with therapeutic response maintained in most patients at 15 mo . Single neridronate and zoledronate infusion showed a similar efficacy in up to 90 % of patients nonresponders to pamidronate . INTRODUCTION Intravenous bisphosphonates represent a common therapy for Paget 's disease of bone ( PDB ) . However , there have been few head to head r and omized trials comparing intravenous bisphosphonates . MATERIAL S AND METHODS We performed a 15-mo , r and omized study comparing different intravenous bisphosphonates in 90 subjects with active PDB . At baseline , patients were r and omly assigned to receive pamidronate ( 30 mg , i.v . , for 2 consecutive days every 3 mo ; n = 60 ) or zoledronate ( 4 mg , i.v . ; n = 30 ) . After 6 mo , nonresponders to pamidronate were crossed over to zoledronate or neridronate ( 100 mg , i.v . , for 2 consecutive days ) . The primary efficacy endpoint was therapeutic response at 6 mo , defined as normalization of alkaline phosphatase ( ALP ) or a reduction of at least 75 % in total ALP excess . RESULTS At 6 mo , 97 % of patients receiving zoledronate had a therapeutic response compared with 45 % of patients receiving pamidronate . Normalization of ALP was achieved in 93 % of patients in the zoledronate group and in 35 % of patients in the pamidronate group . ALP normalization was maintained in 79 % and 65 % of zoledronate-treated patients after 12 and 15 mo , respectively ; loss of therapeutic response was observed in 2 of 30 ( 6 % ) at 12 and 15 mo . At 6 mo , 27 patients showing therapeutic response to pamidronate continued the treatment , whereas nonresponders were crossed-over to neridronate ( n = 15 ) or zoledronate ( n = 18 ) . Among these subjects , 14 of 15 ( 93 % ) in the neridronate group and 17 of 18 ( 94 % ) in the zoledronate group achieved a therapeutic response . Similar normalization rates were observed between neridronate- ( 80 % ) and zoledronate- ( 83 % ) treated subjects . Normalization and therapeutic response were maintained at 9 mo from treatment ( corresponding to 15 mo from the baseline visit ) in either neridronate or zoledronate groups . CONCLUSIONS Single neridronate and zoledronate infusion showed a similar efficacy in achieving biochemical remission in up to 90 % of patients nonresponders to pamidronate . Therapeutic response to zoledronate seems to be maintained in most patients at 15 mo Chloro-4-phenyl thiomethylene bisphosphonate ( tiludronate ) is a new drug which can be used as an inhibitor of bone resorption . As it remains in bone for a long time , and as mineralisation defects have only been seen at doses much higher than those required to decrease osteoclastic activity , it could be given at high doses over a short period of time . Eighteen patients with Paget 's disease of bone were r and omly allocated to three therapeutic groups receiving respectively 600 , 800 , and 1200 mg/day tiludronate for five days . Serum alkaline phosphatase activity and the urinary hydroxyproline/creatinine ratio were quickly and drastically reduced in all three groups . A significant reduction of serum alkaline phosphatases and the hydroxyproline/creatinine ratio was still present six months after the five day therapeutic course , reflecting a sustained activity of tiludronate even after stopping treatment . Dose dependent short and long term reductions of bone turnover rate were observed . Biochemical assessment of haematological , renal , or hepatic tolerance did not show any toxicity of tiludronate . Fifty per cent of patients treated by a dose of 1200 mg/day reported gastrointestinal disturbances , however , making this dosage unsuitable for clinical practice We studied four treatment regimens of oral alendronate in 60 patients with active Paget 's disease . Two groups received an oral daily dose of either 40 or 80 mg of alendronate for 3 months , followed by placebo for a further 3 months : the other two groups received treatment with 40 or 80 mg per day for 6 months . Activity of alkaline phosphatase and urinary hydroxyproline excretion were measured before , during , and after treatment , at intervals for a total follow-up of 1 year . A transiliac bone biopsy was performed in 24 patients before and after the treatment . An additional 16 patients had a third biopsy more than a year after stopping treatment . Alendronate induced a marked suppression in the urinary excretion of hydroxyproline within 2 weeks ( p < 0.01 ) followed by a fall in serum activity of alkaline phosphatase at 1 month ( p < 0.01 ) in all treatment groups . Nine months after the start of treatment patients treated with 80 mg for 6 months had a significantly lower mean alkaline phosphatase activity compared to the other treatment groups ( p < 0.02 ) , which persisted at 1 year ( p < 0.05 ) . Alkaline phosphatase decreased to within the laboratory reference range in all patients given 80 mg for 6 months . In contrast , alkaline phosphatase decreased to within the laboratory reference range in 73 - 83 % of patients given 80 mg for 3 months and the 40 mg dose . Histomorphometric assessment showed a decrease in indices of bone turnover in the pagetic biopsies . None of the biopsies taken after treatment showed evidence of impaired mineralization of bone . Gastrointestinal side effects occurred in 25 % of patients of whom two withdrew from treatment . We conclude that oral alendronate is an effective agent for the treatment of Paget 's disease of bone Using data from the Belgian Paget ’s Disease Registry of 142 patients treated with a 5 mg intravenous infusion of zoledronic acid , we examined disease remission over 3 years in 98 patients with Paget disease of bone ( PDB ) seen in routine practice . Median age was 76 years , most patients ( 60.2 % ) were male , and all were Caucasian . Median time since PDB diagnosis was 11.5 years , few patients ( 5.1 % ) had a family history of PDB , and 32.6 % had received prior bisphosphonate and /or other treatments . The most common pagetic locations were pelvis , spine , femur , tibia , and skull . The most common symptoms included pain , impaired mobility , bone deformities , and joint disease : 36.7 % of patients had comorbid osteoarthritis and 16.3 % comorbid osteoporosis . Response rates were 93.3 % at 1 year , 89.5 % at 2 years , and 91.6 % at 3 years , statistically similar to an extension study of the original zoledronic acid trials . Twenty-one patients experienced a relapse over the 3-year period at a median of 20.7 months posttreatment ; of these , 13 regained remission by the end of the observation period . Relapse was not associated with osteoarthritis , osteoporosis , or other comorbidities . Safety data were similar to those reported elsewhere . In summary , in this somewhat frailer sample of patients with PDB , effectiveness and safety data were similar to those observed in the original trial population s. These findings , which are the first on the use of zoledronic acid for PDB in routine clinical practice , underscore the therapeutic benefits and relative safety of zoledronic acid in the management of PDB in “ real-world ” clinical setting OBJECTIVE To assess the optimal dosage of oral tiludronate in Paget 's disease of bone . METHODS We studied 149 patients with Paget 's disease , in a double-blind , r and omized , placebo-controlled trial . Patients were r and omly assigned to 1 of 5 therapeutic groups : a daily dose of 100 mg , 200 mg , 400 mg , or 800 mg of oral tiludronate , or a placebo . Treatment was for 3 months , followed by 3 months of placebo-controlled followup . Serum alkaline phosphatase activity ( SAP ) and fasting urinary excretion of hydroxyproline/creatinine ( OH/Cr ) were measured monthly , as were biochemical parameters reflecting renal , hepatic , and hematologic functions . Analgesic efficacy was self-evaluated from a visual analog scale and a global pain index . RESULTS Statistical analysis revealed that beginning at a dosage of 200 mg/day , there was a direct dose-dependent effect on the reduction of SAP and OH/Cr levels . Reduction of SAP levels was clinical ly significant at a dosage of 400 mg ( 44.9 + /- 4.2 % reduction at 90 days and 49.2 + /- 4.5 % at 180 days , mean + /- SEM ) and at 800 mg ( 53.4 + /- 5 % at 90 days and 59.3 + /- 4.6 % at 180 days ) . There was a significant reduction in pain in all groups , including the group taking placebo . In only those taking 800 mg/day of tiludronate was there a significant frequency of complete resolution of pain ( versus placebo ) . Aside from mild gastrointestinal disturbances , as experienced with other oral bisphosphonates , clinical tolerance of all 5 regimens was good . Exhaustive biochemical investigations failed to reveal significant toxicity of tiludronate up to the 800-mg daily dose investigated . CONCLUSION Because of its significantly better antiresorptive effects and greater analgesic properties ( compared with lower dosages ) , combined with the excellent clinical and biochemical tolerance , the 800-mg daily dose of tiludronate appears to be optimal for the treatment of Paget 's disease of bone We studied the effects of intravenous alendronate on disease activity in 36 patients with active Paget 's disease of bone . Alendronate was administered to 3 groups of 12 patients at doses of 2.5 , 5 , and 10 mg intravenously daily for 5 consecutive days . The patients were matched for disease activity . Symptomatic improvement was seen in at least 10 patients in each treatment group . Alendronate induced a dose-dependent suppression of biochemical indices of bone turnover in all patients . A significant reduction in the mean fasting urinary excretion of hydroxyproline occurred within 2 days of starting treatment , reaching a nadir at 2 - 4 weeks , which was most marked in patients receiving 10 mg of alendronate ( p < 0.05 ) . There was a slower fall in serum alkaline phosphatase activity with maximal suppression occurring 3 months after the start of treatment . The degree of suppression was least for those receiving 2.5 mg of alendronate ( p < 0.05 ) but no difference in response was observed for the other dosages . The duration of response was also dose-related . A significant fall in the serum calcium and urinary excretion of calcium occurred from the second day of treatment but returned to pretreatment values by 4 months . A transient fall in the mean lymphocyte count was observed , which was similar for each group . This was associated with a short-lived fever in 3 patients receiving 10 mg , in 4 patients receiving 5 mg , and in 2 patients receiving 2.5 mg . ( ABSTRACT TRUNCATED AT 250 WORDS In summary , the clinical efficacy studies provide clear evidence that treatment with oral alendronate markedly suppresses bone turnover and produces clinical improvement in pagetic patients . Serum alkaline phosphatase was greatly decreased by treatment , and the response to alendronate was superior to that observed for currently available therapies such as etidronate and calcitonin , which usually reduce alkaline phosphatase , on average , by 40%-50 % . Alendronate also markedly reduced urinary resorption markers and induced radiologic improvement of pagetic osteolysis . A majority of alendronate-treated patients normalized their serum alkaline phosphatase by month 6 . This observation is likely to be relevant to the duration of response to treatment , as previous studies have shown that the degree of suppression of alkaline phosphatase after antiresorptive treatment correlates with the duration of remission . Therefore , patients who responded to treatment with alendronate , especially those who normalized their alkaline phosphatase levels , are likely to maintain the biochemical remission for several years . Indeed , preliminary unpublished data seem to indicate that alendronate is capable of producing long-term biochemical remission in the majority of patients . In addition to its efficacy , the safety and tolerability profile of alendronate 40 mg/day was very favorable and , overall , comparable to that of placebo A double-blind , r and omized , placebo-controlled study was performed to evaluate the effect of oral tiludronate therapy in 139 patients with active Paget 's disease of bone . Patients received placebo ( N = 48 ) , tiludronate 200 mg ( N = 45 ) , or tiludronate 400 mg ( N = 46 ) once daily for 12 weeks . Biochemical and clinical responses were observed during the 12 week treatment phase and during an additional 12 week observation phase of the study . Both the 200 and 400 mg tiludronate groups experienced significant reduction in serum alkaline phosphatase ( SAP ) and urinary indices of bone resorption . After 12 weeks of therapy , the SAP levels decreased 46 % from baseline values in the 200 mg group and 51 % from baseline values in the 400 mg group . At the end of the 24 week study , SAP levels were reduced 47 % and 58 % from baseline in the 200 and 400 mg groups , respectively . The SAP reduction at 24 weeks was greater in the 400 mg group than the 200 mg group ( p < 0.05 ) . At the end of 24 weeks , 51 % of patients treated with 200 mg and 72 % of those who received 400 mg of tiludronate had experienced a reduction in SAP of greater than 50 % ( p = 0.043 ) , and 7 % and 35 % of patients in the 200 and 400 mg groups , respectively , had experienced normalization of SAP ( p = 0.001 ) . There was no difference in incidence of side effects in patients taking tiludronate or placebo . In conclusion , oral tiludronate is an effective and well-tolerated therapy for patients with Paget 's disease of bone . Daily therapy with 400 mg tiludronate for 12 weeks is more effective than a daily dose of 200 mg for 12 weeks We report a r and omized placebo-controlled double-blind study of amino-hydroxybutylidene bisphosphonate ( alendronate ) , infused over 1 h , in 15 patients with Paget 's disease of bone . Alendronate , 10 mg/day for 5 days , suppressed urinary hydroxyproline to 44.9 + /- 4.8 % and serum alkaline phosphatase to 74.6 + /- 5.4 % of their pretreatment values within 1 month of the start of treatment . Within 5 months of the start of treatment serum alkaline phosphatase fell to 47.9 + /- 6.3 % of pretreatment values . These effects were associated with a decrease in serum calcium and phosphate and in urinary calcium excretion and with a rise in serum iPTH values . A transient fever was observed in 3 of 10 patients who received alendronate during the course of the infusions , and this was associated with a decrease in the total and differential white cell count . No adverse effects were noted on renal function as judged by glomerular filtration rate and indices of proximal and distal tubular function . This regimen may simplify the management of patients with Paget 's disease of bone A multicentre , r and omised , placebo-controlled , dose-ranging study was conducted to investigate the therapeutic activity and sustained efficacy of tiludronate ( 200 mg , 400 mg and 600 mg once daily ) taken orally for 12 weeks in patients with Paget 's disease . Serum alkaline phosphatase concentrations were compared with baseline at weeks 12 and 24 ; treatment success was defined as a 50 % reduction compared with baseline . Changes in the hydroxyproline : creatinine ratio were also measured . Pain was assessed using the Huskisson Visual Analogue Scale and by question naire . Patients completing at least 11 weeks of treatment were followed-up 18 months later by postal question naire . Significantly greater numbers of patients in the tiludronate groups successfully responded to treatment compared with the placebo group . A dose-response was observed ; the percentage of patients responding to treatment being 31 % ( 200 mg ) , 52 % ( 400 mg ) and 82 % ( 600 mg ) at week 12 and 45 % ( 200 mg ) , 70 % ( 400 mg ) and 82 % ( 600 mg ) at week 24 . Tiludronate treatment also significantly reduced hydroxyproline : creatinine ratios compared with placebo , again showing a dose response . Dose-related gastrointestinal symptoms were the commonest adverse events , occurring in 2.4 % , 11.0 % , 5.5 % and 18.9 % of patients receiving placebo and tiludronate 200 , 400 and 600 mg daily , respectively . The response to oral tiludronate was sustained for more than 18 months in some patients and there was evidence of a reduction in the longer term complications of the disease . These results show that oral tiludronate is an effective , well-tolerated treatment for Paget 's disease ; the 400 mg once daily dose appears to offer the optimum balance of efficacy and tolerance AIMS To describe the effects of two consecutive intravenous infusions of aminohexane bisphosphonate ( Neridronate ) in patients with active Paget 's disease of bone . METHODS The study population included 83 patients , aged 41 to 85 years , r and omized to 4 cumulative doses of Neridronate ( 25 , 50 , 100 , 200 mg ) given over 2 days , with a follow up of 180 days . The baseline serum alkaline phosphatase activity was at least 10 % above the upper limit of the laboratory range . The response to treatment was assessed by changes in the serum total alkaline phosphatase ( primary end point of the study ) , bone alkaline phosphatase and N-telopeptide urinary excretion . RESULTS All Neridronate doses significantly suppressed the biochemical indices of disease activity . The nadir of total alkaline phosphatase levels ranged from -16 % to -57.5 % of pretreatment values in the four groups , with a dose-response relationship that was apparent even between the two highest doses . The proportion of patients still maintaining a partial response ( decreases in serum total alkaline phosphatase > 25 % ) at the 6 month follow-up was also related to the dose : 98 % , 67 % , 57 % , 21 % in the patients given 200 , 100 , 50 , 25 mg respectively . The proportion of responders in terms of bone alkaline phosphatase and N-telopeptide excretion changes was similar . Bone pain attributed to Paget 's disease was significantly reduced . A typical acute phase reaction ( fever and /or arthromyalgia ) occurred in 16 out of 83 patients . CONCLUSIONS We conclude that all of the Neridronate doses tested here were well tolerated and effective in decreasing , in a dose-related manner the bone turnover parameters of Paget 's disease . The highest dose ( 200 mg ) result ed in the normalization of the markers of disease activity in more than 60 % of the patients Effective pamidronate dosages in Paget 's disease of bone have not yet been determined . We prospect ively compared two pamidronate dosages ( 60 mg and 120 mg ) in 26 patients whose baseline alkaline phosphatase level was at least two-fold the upper limit of normal . Pamidronate was given as three-hour infusions of 60 mg each . Follow-up was two years . The two groups were comparable at baseline except for higher alkaline phosphatase and hydroxyproline levels in the group treated with 120 mg pamidronate . Efficacy on laboratory parameters was greater in the higher dosage group . Osteocalcin levels showed little change . In both dosage groups , alkaline phosphatase levels fell significantly versus baseline , and the difference persisted throughout the two-year follow-up . Urinary hydroxyproline excretion remained significantly reduced versus baseline during the first 12 months and rose subsequently . A return to normal of the two study parameters six months after treatment was associated with longer duration of the biologic treatment response . A survival curve analysis confirmed this finding and suggested that a return to normal of laboratory parameters was predictive of clinical remission . The drug was well tolerated . Adverse effects were mild and similar to those recorded during earlier studies Second and third generation bisphosphonates are the treatment of choice for Paget 's disease of bone . These drugs are more effective than calcitonin and etidronate , but there have been no head to head , r and omized controlled trials comparing potent bisphosphonates . We conducted a 2-year , r and omized , open-label trial comparing oral alendronate and intravenous pamidronate in 72 subjects with Paget 's disease . R and omization was stratified according to baseline plasma total alkaline phosphatase ( ALP ) and previous bisphosphonate treatment ( yes or no ) . All previously treated patients had received pamidronate but not alendronate . Assigned treatments were pamidronate ( 60 mg ) every 3 months as a single infusion or alendronate ( 40 mg ) daily in 3-month blocks , continued until biochemical remission ( defined as both ALP and urine deoxypyridinoline (DPD)/creatinine ratio in the reference range ) or a clear plateau effect was observed . At 1 year , nonresponders to pamidronate were crossed over to alendronate treatment . At 1 year , 31/36 ( 86 % ) subjects r and omized to alendronate achieved biochemical remission compared with 21/36 ( 56 % ) for pamidronate ( P = 0.017 ) . There was a significantly greater reduction in ALP ( P < 0.001 ) and DPD/creatinine ratio ( P < 0.001 ) for alendronate compared with pamidronate treatment . In previously untreated patients , alendronate result ed in remission in 20/22 ( 91 % ) subjects compared with 19/22 ( 86 % ) of pamidronate-treated subjects , which was not significantly different ; however , alendronate result ed in a significantly greater reduction in ALP ( P = 0.014 ) and DPD/creatinine ratio ( P < 0.001 ) . In previously treated patients , alendronate result ed in remission in 11/14 ( 79 % ) subjects compared with 2/14 ( 14 % ) for pamidronate ( P < 0.001 ) , with a significantly ( P < 0.001 ) greater reduction in both ALP and DPD/creatinine ratio . Of subjects crossed over from pamidronate to alendronate , 10/14 ( 71 % ) achieved remission , including 9/11 ( 82 % ) previously treated patients . We conclude that , in patients with previously untreated Paget 's disease of bone , alendronate and pamidronate have similar efficacy in achieving biochemical remission . In patients previously treated with pamidronate , alendronate is more effective OBJECTIVES Hearing loss has long been known to be a complication of Paget 's disease of bone . The aim of this study was to investigate Paget 's disease of the temporal bone with special attention to hearing loss . METHODS Twenty-five patients with skull involvement were treated with either pamidronate or tiludronate . Imaging included radiography , quantitative bone scintigraphy ( QBS ) , single photon emission computed tomography ( SPECT ) and high-resolution computed tomographic ( H RCT ) scanning . Audiometric assessment was also performed . RESULTS Twenty-three of the 25 patients with skull involvement suffered from hearing loss . Bisphosphonate treatment result ed in a decreased serum total alkaline phosphatase ( serum tAP ) level and QBS ratio , and also seemed to improve the complaints of the patients . H RCT demonstrated involvement of the middle ear ossicles ( n = 7 ) , involvement of the petrous pyramids ( n = 14 ) , demineralization of the otic capsule ( n = 10 ) , porosis pericochlearis ( n = 8) , narrowing of the external auditory meatus ( n = 12 ) , mastoid process thickening ( n = 5 ) and stapedial footplate thickening ( n = 4 ) . The audiometric examination did not show any significant changes 1 yr after bisphosphonate treatment . CONCLUSIONS H RCT imaging is a well suited tool for demonstrating the complication of Paget 's disease . QBS and measurement of serum tAP level may also be regarded as useful techniques for monitoring treatment . However , hearing may remain impaired in spite of the improved scintigraphy and laboratory parameters , therefore , audiometric assessment is also important in pagetic patients with skull involvement In order to evaluate and quantitate the therapeutic efficacy of disodium etridonate ( EHDP ) in the treatment of Paget 's disease , a prospect i ve double-blind study was instituted . Subjects received either placebo , low-dose EHDP , or high-dose EHDP and were evaluated prior to therapy and 6 months later . Bone scans were performed with 99mTc or 18F and radioisotopic uptake studies were conducted . The results were correlated with clinical improvement , biochemical parameters , and radiographic skeletal surveys , and indicate that the radioisotopic uptake studies are both a sensitive and reproducible means of evaluating the degree of response to EHDP Twenty patients with mild Paget 's disease of bone were given either 20 ( 10 patients ) or 40 mg alendronate daily for 6 months . The 20-mg dose was well tolerated , but in 3 patients on 40 mg/d alendronate , the treatment was withdrawn after 3 - 5 months because of gastric and oesophageal disturbances . Urinary hydroxyproline excretion fell within the first month to 77 + /- 5 % ( SD ) and to 47 + /- 5 % of pretreatment values in the 20- and 40-mg dosing group , respectively ( p < 0.001 between group comparison ) . The serum alkaline phosphatase fell more slowly with the maximum suppression of disease activity reached at 4 months , when it attained a plateau in both groups of patients . However , the decrease in serum alkaline phosphatase was significantly more pronounced in the patients treated with 40 mg/d tablets ( 50 + /- 10 % of pretreatment values ) than in those given 20 mg alendronate per day ( 76 + /- 9 % of initial value ) , in none of whom a disease remission was observed . It appears , therefore , that while 20 mg/d oral doses of alendronate are insufficient , 40 mg/d are associated with a high incidence of side effects . Furthermore , the suppression of disease activity depends on the dose of bisphosphonate given daily or over a short period of time and lower doses can not be compensated by a longer duration of the treatment course A long-term trial of etidronate disodium therapy in 93 patients with Paget 's disease of bone yielded generally favorable results . Treatment or retreatment was initiated for symptomatic Paget 's disease with elevated serum alkaline phosphatase and urinary hydroxyproline values . Improvement occurred in 60 percent of patients even in the presence of secondary osteoarthritis . There appeared to be three types of responses : ( 1 ) Patients with prolonged clinical and chemical improvement after a single course of therapy ( 40 percent ) ; these patients tended to have less active disease on the basis of initial alkaline phosphatase and hydroxyproline values , with suppression to normal in 76 percent of patients after etidronate disodium therapy . ( 2 ) Patients with response to retreatment ( 45 percent ) ; these patients had modest disease on the basis of alkaline phosphatase and hydroxyproline values and required retreatment less often than once a year . ( 3 ) Patients with response to retreatment but eventual development of resistance to etidronate disodium ( 15 percent ) ; these patients had the most severe disease clinical ly and on the basis of alkaline phosphatase and hydroxyproline values . In this last group , resistance to etidronate disodium ( 5 mg/kg per day ) was common and early , and patients received etidronate disodium more often than one course per year ; alkaline phosphatase response was transient , often of less than three months ' duration Bisphosphonates have been shown to be effective in treating the increased bone turnover associated with Paget 's disease of bone . In this study two groups of patients were treated with pamidronate by intravenous infusion . In group 1 ( n = 15 ) 30 mg of pamidronate was given once a week for six weeks . A subgroup ( group 1A , n = 6 ) of more severely affected patients ( pretreatment serum alkaline phosphatase ( ALP ) greater than 1000 U/l , normal range 80 - 280 U/l ) received a further 60 mg weekly for three weeks . Group 2 ( n = 24 ) received 45 mg of pamidronate every three months for one year . In both groups the level of ALP in serum sample s decreased steadily throughout the year . In group 1 the level decreased to a mean value of 230 U/l ( 95 % confidence interval 188 - 281 ) and in group 2 to 297 U/l ( 227 - 389 ) . Four of the six patients in group 1A achieved normal ALP , whereas ALP remained at an increased level in all of the 10 patients in group 2 whose pretreatment ALP was greater than 1000 U/l , suggesting that a dose-response effect exists . The lowest hydroxyproline to creatinine ratios ( normal ratio less than 0.033 ) were observed at the end of treatment in group 1 , with a mean ratio of 0.022 ( range 0.015 - 0.033 ) and at three months after the start of treatment in group 2 with a mean ratio of 0.029 ( range 0.022 - 0.037 ) . There was a significant decrease in the turnover of bone , as measured by whole body retention of radiolabelled bisphosphonate , from a mean of 49.3 to 41.0 % ( p less than 0.01 ) . These data confirm that pamidronate is effective in the management of Paget 's disease of bone . For patients with levels of ALP in serum sample s of up to four times above the upper limit of the normal reference range , an effective and convenient regimen is 45 mg every three months for one year . For patients with higher levels of ALP higher doses may be more effective Clodronate and alendronate were compared in 27 patients with active Paget 's bone disease . Carboxyterminal crosslinked telopeptide of type I collagen ( ICTP ) was evaluated as a marker of bone turnover in Paget 's bone disease . Group 1 . Nineteen patients received clodronate infusions ( 300 mg/daily ) on 5 consecutive days . After 1 year , 12 patients ( 63 % ) were still in remission ; urinary hydroxyproline ( 64.8 % ) and serum alkaline phosphatase ( 59.4 % ) were significantly reduced and had returned to normal in 30 % . Patients in remission had significantly higher basal values of urinary hydroxyproline . No adverse side effects were observed . Group 2 . One year after clodronate , seven relapsing patients retrospectively underwent five consecutive infusions of alendronate ( 5 mg/daily ) . Within 12 months , urinary hydroxyproline fell by 74.7 % , alkaline phosphatase dropped by 75.2 % , osteocalcin by 47.3 % , and ICTP by 56.4 % . In all patients , urinary hydroxyproline and alkaline phosphatase returned to normal within 3 months and remained within the normal range during the 12-month follow-up . Most patients had mild , short course fever and arthromyalgia . Group 3 . Eight newly diagnosed pagetics , received alendronate alone ( 5 mg/daily for 5 days ) . All patients responded well to alendronate within the first month . None suffered a relapse during the follow-up . At month 12 , urinary hydroxyproline was down by 71.4 % , alkaline phosphatase by 75.3 % , osteocalcin by 58.1 % , and ICTP by 67.4 % . In all patients , markers of bone remodeling were in the normal range at the end of the follow-up . Moderate , transitory arthromyalgia , and fever ( high and lasting for 7 days in only one case ) were observed in half of the patients . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE We have previously shown that the woven pagetic bone in patients with Paget 's disease is characterized by an impaired degree of beta-isomerization of C-telopeptides of type I collagen molecules , which results in a preferential urinary excretion of nonisomerized type I collagen C-telopeptide breakdown products ( CTX ) . The aim of this study was to measure the urinary excretion of nonisomerized ( alpha ) and beta-isomerized ( beta ) CTX in patients with Paget 's disease treated with a bisphosphonate . METHODS We studied 28 patients with active Paget 's disease of bone who were a part of a r and omized , double-blind , placebo-controlled study comparing the effects of several doses of a single injection of zoledronate , a new potent bisphosphonate . Serum bone alkaline phosphatase ( BAP ) and type I collagen C-terminal extension propeptide ( PICP ) and urinary excretion of free deoxypyridinoline ( free D-Pyr ) , N-telopeptide breakdown products ( NTX ) , alphaCTX , and betaCTX were measured at baseline and 5 , 10 , 30 , and 60 days after injection . RESULTS At baseline , all markers were significantly increased in the patients compared with a group of 97 sex- and age-matched controls , with a greater increase in BAP ( 12-fold ) , NTX ( 19-fold ) , and alphaCTX ( 10-fold ) compared with PICP ( 2.2-fold ) , free D-Pyr ( 2.5-fold ) , and betaCTX ( 3-fold ) . The ratio of alphaCTX to betaCTX was about 3-fold higher than in controls ( 2.1 versus 0.76 ; P < 0.001 ) . After a single intravenous injection of zoledronate ( 200 or 400 microg ) , all markers decreased within 5 days , except for BAP and free D-Pyr , which decreased on day 10 . The maximum decrease was greater and occurred faster for NTX , alphaCTX ( -55 % after 10 days ) , and betaCTX ( -42 % after 10 days ) than for free D-Pyr ( -25 % after 30 days ) . After the initial decrease , the urinary excretion of betaCTX increased between days 10 and 30 and returned to pretreatment levels after 2 months , in contrast to the sustained decrease in alphaCTX and NTX that was maintained up to 60 days . The urinary ratio of alphaCTX to betaCTX decreased significantly between days 10 and 60 , and returned to within the normal range in most patients after 2 months of treatment , probably reflecting the progressive replacement of woven bone by a lamellar bone with a higher and normal degree of beta-isomerization of type I collagen , as previously documented by histology . CONCLUSION The determination of the urinary ratio of alphaCTX to betaCTX could be useful for monitoring the effect of bisphosphonate treatment in restoring bone quality in patients with Paget 's disease An intravenous dosage schedule using pamidronate disodium , based on biochemical severity , was used to treat 71 patients with Paget 's disease who had no previous bisphosphonate treatment . Disease severity was stratified by fasting hydroxyproline excretion ( HypE ) : Group ( Gp ) I ( mild disease ; HypE < 5.0 mumol/LGF ) received a total dose of 120 mg ; Gp II ( moderate ; HypE 5.00 - 9.99 ) received 180 mg ; and Gp III ( severe ; HypE > or = 10 ) received 240 mg . Within each group patients were r and omly allocated to receive daily 30 mg or 60 mg infusions . Observations for 2 years included pain scores , indices of bone turnover , and radiology of lytic lesions . There was no difference in biochemical responses , or in the percentage of patients with early fever , between the 30 mg and 60 mg daily subgroups ; for convenience , 60 mg infusions are recommended . Neutrophils and total white cell counts were both significantly below baseline 4 days after the first infusion ; lymphocytes were significantly reduced by day 2 ; and all three measures had returned to within the reference range by day 6 . Remission was assessed at 6 months , when both plasma alkaline phosphatase ( ALP ) and HypE had reached stable nadirs . Increasing severity was associated with increasing resistance to suppression of HypE at 6 months to within the reference range : Gp I , 87 % ; Gp II , 44 % ; and Gp III , 0 % ( p < 0.0001 by chi-square test ) . Biochemical relapse at 2 years ( defined as ALP 50 % above the 6 month level ) was also dependent on initial disease severity ( Gp I , 6 % ; GpII , 39 % ; Gp III , 62 % ; p < 0.0005 by chi-square test ) . There was no association between time to relapse and either initial dose or log dose . Radiologic lytic lesions ( in 22 patients ) were all in remission at 3 months ; however , relapse rates at 2 years appeared to be severity-dependent : Gp I , 13 % ; Gp II , 43 % ; and Gp III , 57 % ( n.s . by chi-square test ) . Remission rates based on a fall to < 50 % of pretreatment of either HypE or ALP were more in accord with lytic lesion remission rates than were rates based on HypE falling to within the reference range . Pamidronate produced a significant reduction from baseline in Pagetic bone , Pagetic joint , and unrelated musculoskeletal pain in the first 6 months ( p < 0.0001 ) . From 0 months to 2 years the maintenance of improvement in bone pain ( p < 0.005 ) and joint pain ( p < 0.05 ) was significantly better than in unrelated pain . Pamidronate is a safe , welltolerated , and effective treatment for Paget 's disease . In spite of larger dosage in severe disease , increasing severity was associated with resistance to normalization of biochemistry and a higher incidence of biochemical and radiological relapse at 2 years . Our current dosage recommendation would be for two 60 mg infusions for mild disease ( Gp I ) ; and four 60 mg infusions for moderate disease ( Gp II ) . Severe disease ( Gp III ) remains a challenge ; regardless of dosage , the majority of patients will be in relapse 2 years after a single course of treatment Abstract A six-month double-blind controlled study was performed to determine effectiveness and dose response of disodium etidronate on Paget 's disease ( osteitis deformans ) . Forty-seven subjects were studied with pain related to radiologically documented Paget 's bone sites as well as marked elevation of serum alkaline phosphatase and hydroxyproline excretion . There was significant ( p<0.05 ) reduction of alkaline phosphatase , hydroxyproline and radiofluoride or radiostrontium uptake over Paget 's bone lesions after orally administered disodium etidronate at doses of 5 , 10 and 20 mg per kilogram per day for six months . There was a dose-response relation of administered disodium etidronate to improvement of pain , with moderate or marked improvement of pain in six of seven subjects on 20 mg per kilogram per day . In all dosage groups the most marked relief of pain was at sites of Paget 's involvement of long bones . Apparent side effects were limited to occasional abdominal cramps . ( N Engl J Med 289:1379–1384 , 1973 The effects of EHDP ( 20 mg/kd/day ) and APD ( 4.5 mg/kg/day ) given for three months to patients with severe symptomatic Paget 's disease have been compared in an open trial of 17 patients . Both drugs were equally effective in producing a prompt reduction in pair scores , urine hydroxyproline , and serum alkaline phosphatase levels . The remission was maintained for a variable period after stopping treatment . Both drugs were well tolerated , and a one-month course of either drug was not effective . Comparison with published responses from previous studies indicates that EHDP given at this dose as a relatively short course is more effective than a lower dose for a longer period of time ; the present study does not suggest that APD has significant advantages A double-blind crossover study was performed in which 50 symptomatic patients with Paget disease were treated with sodium etidronate ( EHDP ) doses of 1 , 2.5 , 5 , 10 , or 20 mg/kg or were given placebo . After six months , the patients were reassigned to treatment with placebo or sodium etidronate , 5,10 , or 20 mg/kg . Sodium etidronate in dosages of 5,10 , or 20 mg/kg/day result ed in significant improvement in levels of serum alkaline phosphatase and urinary hydroxyproline , as well as clinical symptoms and bone scans . Bone scans and urinary determinations showed statistically greater improvement with sodium etidronate 20 mg/kg , in comparison to patients who received sodium etidronate 5 mg/kg for 12 months . After withdrawal of effective therapy , five of nine patients continued to have remission of their symptoms with placebo for an additional six months . ( JAMA 230:562 - 567 , 1974 Paget ’s disease is characterized by an excessive enhancement of bone turnover due to increased osteoclastic bone resorption . Antiresorptive drugs , like calcitonins or bisphosphonates , are therefore used in the treatment of Paget ’s disease . At present , bisphosphonates are considered the treatment of choice . The usefulness of bisphosphonates like etidronate or tiludronate is limited to less severe cases , due to their comparatively low antiresorptive potency . More potent bisphosphonates like pamidronate or alendronate are frequently associated with gastrointestinal side effects , when given orally , another problem is poor and variable gastrointestinal resorption . Therefore , intravenous application of bisphosphonates has several advantages . With clodronate and pamidronate , however , the application has to be via intravenous infusion to avoid the risk of renal damage . Ib and ronate is a new aminobisphosphonate with a 50-fold higher biological activity than pamidronate in vitro . Two milligrams can be administered safely as an intravenous injection , thus providing a new mode of application for intravenous biphosphonate therapy . We report here our experiences with intravenous ib and ronate in Paget ’s disease of bone . We compared the efficacy and tolerability of intravenous injection vs. infusion of 2 mg ib and ronate , investigated the efficacy of a repeat treatment after relapse of disease activity , and assessed the effects of a dose escalation to 4 and 6 mg ib and ronate Bisphosphonates have been suggested to be partially chondroprotective in animal models of arthritis . The aim of this study was to assess the short-term effect of the bisphosphonate zoledronate on type II collagen degradation in patients with Paget 's disease of bone . Twenty-six patients with active Paget 's disease who were a part of a double-blind , placebo-controlled , r and omized study comparing the effects of several doses of a single injection of zoledronate , a potent bisphosphonate , were studied . Type II collagen destruction was assessed by urinary levels of type II collagen C-telopeptide ( CTX-II ) using a new immunoassay . Bone resorption was assessed by measuring the urinary excretion of nonisomerized type I collagen C-telopeptide ( alpha CTX-I ) . Biochemical markers were measured at baseline and 5 , 10 , 30 , and 60 days after injection . At baseline , no significant increase of CTX-II was observed in patients with Paget 's disease compared with a group of 27 gender- and age-matched controls , in contrast to the ninefold ( p < 0.0001 ) increase of urinary alpha CTX-I. After a single intravenous injection of zoledronate ( 200 or 400 microg ) , urinary CTX-II transiently decreased by a median of 25 % 5 days after the injection of zoledronate ( p = 0.0023 vs. placebo ) , then increased to pretreatment levels after 10 days . In contrast , urinary alpha CTX-I decreased within 5 days with a maximal decrease of 51 % at day 10 ( p < 0.001 vs. baseline and placebo ) , and levels remained suppressed during the 2 months of the study . Zoledronate not only reduces bone turnover but also directly decreases type II collagen degradation in patients with Paget 's disease , suggesting that bisphosphonates may have chondroprotective effects in humans . Measurement of type II collagen breakdown by a new urinary biochemical marker may be useful for in vivo assessment of the effects of drugs that potentially inhibit cartilage destruction 1 Hope Hospital , Salford , UK 2 Department of Clinical Chemistry , Royal Liverpool University Hospitals , Liverpool , UK 3 Nottingham City Hospital , Nottingham , UK 4 Rush Presbyterian – St . Luke ’s Medical Center , Chicago , IL , USA 5 University of Arizona Health Sciences Center , Tucson , AZ , USA 6 John Wayne Cancer Institute , Santa Monica , CA , USA 7 Robert Jones and Agnes Hunt Hospital , Oswestry , Shropshire , UK 8 Osteoporosis Unit , Nuclear Medicine Department , Guy ’s Hospital , London , UK 9 University of Massachusetts Medical School , Worcester , MA , USA 10 State University of New York Health Science Center , Syracuse , NY , USA 11 Duke University Medical Center and VA Medical Center , Durham , NC , USA 12 University of Manchester , Manchester , UK 13 Clinical Research , Novartis Pharmaceuticals , East Hanover , NJ , USA 14 Columbia University College of Physicians and Surgeons , New York , NY , OBJECTIVE To compare the efficacy and safety of tiludronate and etidronate at the same dosage ( 400 mg/day ) for the treatment of active Paget 's disease of bone . METHODS We studied 234 patients with radiologic lesions characteristic of Paget 's disease of bone and serum alkaline phosphatase ( AP ) concentrations at least twice the upper limit of normal , in a prospect i ve , r and omized , double-blind , multicenter clinical trial lasting 6 months . Patients were r and omly allocated into 1 of 3 treatment groups : tiludronate for 3 months followed by placebo for 3 months , tiludronate for 6 months , or etidronate for 6 months . Serum AP levels and urinary hydroxyproline excretion were measured at baseline and after 3 months and 6 months . Patients with a reduction of at least 50 % in the serum AP concentration were considered to be responders . RESULTS After 3 months , the proportion of responders was higher in the tiludronate group ( 57.4 % ) than in the etidronate group ( 13.9 % ) ( P < 0.0001 ) . In the etidronate group , this percentage was lower among patients who had received previous treatment with a bisphosphonate ( 2.3 % ) than among those who had not ( 28.6 % ) ( P < 0.01 ) . Previous bisphosphonate treatment was not associated with response in the tiludronate group . After 6 months , the proportion of responders did not differ between the 2 tiludronate groups ( 60.3 % and 70.1 % ) , but was lower in the etidronate group ( 25.3 % ) ( P < 0.0001 ) . There was a higher proportion of patients with treatment-resistant disease ( < 25 % reduction of serum AP ) in the etidronate group ( 51.9 % ) than in the tiludronate 3-month group ( 17.9 % ) or the tiludronate 6-month group ( 19.5 % ) ( P < 0.0001 ) . Gastrointestinal disturbances were more common , and occurred earlier , with tiludronate , but they were mostly mild , requiring no treatment . CONCLUSION Tiludronate at 400 mg/day for 3 months or 6 months is more effective than the same dosage of etidronate for 6 months in the treatment of Paget 's disease PURPOSE The potent bisphosphonates offer great promise in the management of Paget 's disease of bone , but are currently available only as parenteral preparations in most countries . There is a need for a well-tolerated , oral therapy . Furthermore , none of the currently available therapies have been rigorously demonstrated to heal the lytic bone lesions characteristic of this condition . Alendronate is a potent new oral aminobisphosphonate that has shown promising effects on Paget 's disease in preliminary studies . METHODS We report a double-blind , r and omized comparison of oral alendronate 40 mg/day and placebo over 6 months in 55 patients with Paget 's disease . Efficacy was determined from measurements of biochemical indices of bone turnover ( serum alkaline phosphatase and urine N-telopeptide ) and blinded radiologic assessment of lytic bone lesions . RESULTS N-telopeptide excretion declined by 86 % and serum alkaline phosphatase by 73 % in patients receiving alendronate , but remained stable in patients receiving placebo ( P < 0.001 between groups for both indices ) . Responses were similar whether or not patients had previously received bisphosphonate treatment . Alendronate treatment normalized alkaline phosphatase in 48 % of patients . Forty-eight percent of alendronate-treated patients showed radiologic improvement in osteolysis whereas in the placebo group only 4 % improved ( P = 0.02 for between-groups comparison ) . No patient in either group showed worsening of osteolysis . Bone histomorphometry indicated that alendronate tended to normalize turnover indices . There was no evidence of abnormal mineralization in bone biopsies taken from 12 alendronate-treated subjects . The treatment was well tolerated . CONCLUSION Oral alendronate appears to be a safe and effective therapy for Paget 's disease and results in healing of lytic bone lesions Paget 's disease of bone is characterized by a high bone turnover . Therefore , antiresorbing agents such as bisphosphonates are clearly indicated . However , as they accumulate in the pagetic lesions , they could produce some focal defects of bone mineralization . In a double-blind study , we have had the opportunity to compare the effects of tiludronate and of etidronate ( both at a fixed dose of 400 mg/day orally ) on the radiological changes of 12 patients suffering from Paget 's disease of bone . After breaking the code , good agreement was observed between the radiological evaluations and the applied therapy : All positive bone balances were observed in the tiludronate group , except for three question able densifications in the etidronate group , and the negative bone balances in the etidronate group . This confirms our previous experience with etidronate in Paget 's disease when X-ray films of the lesions are followed sequentially during therapy |
727 | 25,362,239 | When all psychological therapies included this review were combined they were superior to usual care or waiting list in terms of reduction of symptom severity , but effect sizes were small .
Compared with usual care or waiting list conditions , CBT reduced somatic symptoms , with a small effect and substantial differences in effects between CBT studies .
The effects were durable within and after one year of follow-up .
Compared with enhanced or structured care , psychological therapies generally were not more effective for most of the outcomes .
Compared with enhanced care , CBT was not more effective .
The intervention groups reported no major harms .
In daily practice , there is also a substantial proportion of participants not willing to accept psychological treatments for somatoform disorders or MUPS . | BACKGROUND Medically unexplained physical symptoms ( MUPS ) are physical symptoms for which no adequate medical explanation can be found after proper examination .
The presence of MUPS is the key feature of conditions known as ' somatoform disorders ' .
Various psychological and physical therapies have been developed to treat somatoform disorders and MUPS .
Although there are several review s on non-pharmacological interventions for somatoform disorders and MUPS , a complete overview of the whole spectrum is missing .
OBJECTIVES To assess the effects of non-pharmacological interventions for somatoform disorders ( specifically somatisation disorder , undifferentiated somatoform disorder , somatoform disorders unspecified , somatoform autonomic dysfunction , pain disorder , and alternative somatoform diagnoses proposed in the literature ) and MUPS in adults , in comparison with treatment as usual , waiting list controls , attention placebo , psychological placebo , enhanced or structured care , and other psychological or physical therapies . | Background Although cognitive-behavioral therapy for Unexplained Physical Symptoms ( UPS ) is effective in secondary care , studies done in primary care produced implementation problems and conflicting results . We evaluated the effectiveness of a cognitive-behavioral group training tailored to primary care patients and provided by a secondary community mental-health service reaching out into primary care . Methodology /Principal Findings The effectiveness of this training was explored in a r and omized controlled trial . In this trial , 162 patients with UPS classified as undifferentiated somatoform disorder or as chronic pain disorder were r and omized either to the training or a waiting list . Both lasted 13 weeks . The preservation of the training 's effect was analyzed in non-r and omized follow-ups , for which the waiting group started the training after the waiting period . All patients attended the training were followed-up after three months and again after one year . The primary outcomes were the physical and the mental summary scales of the SF-36 . Secondary outcomes were the other SF-36-scales and the SCL-90-R. The courses of the training 's effects in the r and omized controlled trial and the follow-ups were analyzed with linear mixed modeling . In the r and omized controlled trial , the training had a significantly positive effect on the quality of life in the physical domain ( Cohen 's d = 0.38;p = .002 ) , but this overall effect was not found in the mental domain . Regarding the secondary outcomes , the training result ed in reporting an improved physical ( Cohen 's d = 0.43;p = 0.01 ) , emotional ( Cohen 's d = 0.44;p = .0.01 ) , and social ( Cohen 's d = 0.36;p = 0.01 ) functioning , less pain and better functioning despite pain ( Cohen 's d = 0.51;p = < 0.001 ) , less physical symptoms ( Cohen 's d = −.23;p = 0.05 ) and less sleep difficulties ( Cohen 's d = −0.25;p = 0.04 ) than time in the waiting group . During the non-r and omized follow-ups , there were no relapses . Conclusions / Significance The cognitive-behavioral group training tailored for UPS in primary care and provided by an outreaching secondary mental-health service appears to be effective and to broaden the accessibility of treatment for UPS . Trial Registration TrialRegister.nl Abstract Objective : To examine the additional effect of cognitive behavioural therapy for patients with medically unexplained physical symptoms in comparison with optimised medical care . Design : R and omised controlled trial with follow up assessment s six and 12 months after the baseline evaluation . Setting : General medical outpatient clinic in a university hospital . Subjects : An intervention group of 39 patients and a control group of 40 patients . Interventions : The intervention group received between six and 16 sessions of cognitive behavioural therapy . Therapeutic techniques used included identification and modification of dysfunctional automatic thoughts and behavioural experiments aim ed at breaking the vicious cycles of the symptoms and their consequences . The control group received optimised medical care . Main outcome measures : The degree of change , frequency and intensity of the presenting symptoms , psychological distress , functional impairment , hypochondriacal beliefs and attitudes , and ( at 12 months of follow up ) number of visits to the general practitioner . Results : At six months of follow up the intervention group reported a higher recovery rate ( odds ratio 0.40 ; 95 % confidence interval 0.16 to 1.00 ) , a lower mean intensity of the physical symptoms ( difference −1.2 ; −2.0 to −0.3 ) , and less impairment of sleep ( odds ratio 0.38 ; 0.15 to 0.94 ) than the controls . After adjustment for coincidental baseline differences the intervention and control groups also differed with regard to frequency of the symptoms ( 0.32 ; 0.13 to 0.77 ) , limitations in social ( 0.35 ; 0.14 to 0.85 ) and leisure ( 0.36 ; 0.14 to 0.93 ) activities , and illness behaviour ( difference −2.5 ; −4.6 to −0.5 ) . At 12 months of follow up the differences between the groups were largely maintained . Conclusion : Cognitive behavioural therapy seems to be a feasible and effective treatment in general medical patients with unexplained physical symptoms Background Although Cognitive-Behavioral Therapy ( CBT ) is effective for Unexplained Physical Symptoms ( UPS ) , some therapists in clinical practice seem to believe that CBT outcome will diminish if psychiatric comorbidity is present . The result is that patients with a psychiatric comorbidity are redirected from treatment for UPS into treatment for mental health problems . To explore whether this selection and allocation are appropriate , we explored whether CBT outcomes in UPS could be predicted by variables assessed at baseline and used in routine- practice assessment s. Methods Patients ( n=162 ) with UPS classified as undifferentiated somatoform disorder or chronic pain disorder were followed up until one year after they had attended a CBT group training . The time-points of the follow-up were at the end of CBT ( immediate outcome ) , three months after CBT ( short-term outcome ) , and one year after CBT ( long-term outcome ) .CBT outcome was measured using the Physical Component Summary of the SF-36 , which was the primary outcome measure in the r and omized controlled trial that studied effectiveness of the CBT group training . Predictors were : 1 . ) psychological symptoms ( global severity score of SCL-90 ) , 2 . ) personality-disorder characteristics ( sum of DSM-IV axis II criteria confirmed ) , 3 . ) psychiatric history ( past presence of DSM-IV axis I disorders ) , and 4 . ) health-related quality of life in the mental domain ( mental component summary of SF-36 ) . The effect of this predictor set was explored using hierarchical multiple regression analyses into which these predictors had been entered simultaneously , after control for : a. ) pretreatment primary outcome scores , b. ) age , c. ) gender , d. ) marital status , and e. ) employment . Results The predictor set was significant only for short-term CBT outcome , where it explained 15 % of the variance . A better outcome was predicted by more psychological symptoms , fewer personality-disorder characteristics , the presence of a psychiatric history , and a better quality of life in the mental domain . Conclusions As the predictors do not seem to predict CBT outcome consistently over time , the need for selection and allocation of patients for CBT is doubtful . It seems that this would unnecessarily deprive patients of effective treatment . Trial registration Nederl and s Trial Register , Abstract Background Somatoform disorders are characterized by the presence of multiple somatic symptoms without an organic cause that completely explains their symptoms . These patients generate a high cost in health services . We aim to evaluate the effectiveness and feasibility of a cognitive-behaviour therapy ( CBT ) programme , administered in group and individual formats in primary care for patients who are diagnosed with abridged somatization disorder . Method / design Design : Multicentre , r and omized , controlled trial involving 3 groups , one of which is the control group consisting of st and ardized recommended treatment for somatization disorder in primary care ( Smith 's norms ) and the 2 others , the intervention groups , consisting of cognitive-behavioural therapy ( 10 sessions ) administered in individual format ( intervention group 1 ) or in group format ( intervention group 2 ) . Setting : 29 primary care health centres in the province of Zaragoza and 3 primary care health centres in the province of Mallorca , Spain . Sample : N = 204 patients , ( 68 in each of the three groups ) , aged 18–65 years , able to underst and and read Spanish , who fulfil Escobar 's criteria of Abridgged Somatization Disorder ( SSI 4,6 ) , stable with pharmacotherapy over the previous month , and who will remain stable for the next 3 months in the doctor 's opinion , having signed informed consent . Intervention : Control group : St and ardized recommended treatment for somatization disorder in primary care ( Smith 's norms ) . Intervention group : 10 weekly sessions of CBT , following a protocol design ed by Prof. Escobar 's group at UMDNJ , USA . There are 2 different treatment conditions : individual and group format . Measurements : Survey on the use of health services , number and severity of somatic symptoms , anxiety , depression , quality of life and clinical global impression . The interviewers will not know which group the patient belongs to ( blind ) . The assessment s will be carried out at baseline , post-treatment , 6 months and 12 post-treatment . Main variables : Utilization of health services , number and severity of somatic symptoms . Analysis : The analysis will be per intent to treat . We will use the general linear models of the SPSS v.15 statistical package , to analyse the effect of treatment on the result variable ( utilization of health services , number and severity of somatic symptoms ) . Discussion It is necessary to develop more effective psychological treatments for somatoform disorders . This r and omised clinical trial will determine whether cognitive behaviour therapy , both in group or in individual format , is effective for the treatment of these patients .Trial registration Current controlled trials IS RCT OBJECTIVE Our aim was to assess cost-effectiveness of mindfulness-based cognitive therapy ( MBCT ) compared with enhanced usual care ( EUC ) in treating patients with persistent medically unexplained symptoms(MUS ) . METHODS A full economic evaluation with a one year time horizon was performed from a societal perspective . Costs were assessed by prospect i ve cost diaries . Health-related Quality of Life was measured using SF-6D . Outcomes were costs per Quality -Adjusted Life Year ( QALY ) . Bootstrap simulations were performed to obtain mean costs , QALY scores and incremental cost-effectiveness ratios ( ICERs ) . RESULTS MBCT participants ( n=55 ) had lower hospital costs and higher mental health care costs than patients who received EUC ( n=41 ) . Mean bootstrapped costs for MBCT were € 6269 , and € 5617 for EUC ( 95 % uncertainty interval for difference : -€1576 ; € 2955 ) . QALYs were 0.674 for MBCT and 0.663 for EUC . MBCT was on average more effective and more costly than EUC , result ing in an ICER of € 56,637 per QALY gained . At a willingness to pay of € 80,000 per QALY , the probability that MBCT is cost-effective is 57 % . CONCLUSION Total costs were not statistically significantly different between MBCT and EUC . However , MBCT seemed to cause a shift in the use of health care re sources as mental health care costs were higher and hospital care costs lower in the MBCT condition . Due to the higher drop-out in the EUC condition the cost-effectiveness of MBCT might have been underestimated . The shift in health care use might lead to more effective care for patients with persistent MUS . The longer-term impact of MBCT for patients with persistent MUS needs to be further studied In order to determine the health effects of an intervention that reduces the cost of care for somatization disorder ( SD ) patients , 59 primary care physicians were r and omized to receive a psychiatric consultation letter providing treatment recommendations for 73 patients either at baseline or the end of the year-long study . Seventy of these patients ( 96 % ) were followed every 4 months for 1 year by a research assistant blind to r and omization . A year following the intervention , patients of experimental physicians reported greater physical capacity than patients of control physicians ( mean difference = 17.9 , 95 % CI 1.0 - 34.9 ) with a $ 466 reduction ( 95 % CI $ 132-$699 ) in health care charges . In addition to a net 21 % reduction in health care charges for the typical SD patient , the consultation letter improved physical functioning in a group of highly impaired subjects BACKGROUND Reattribution is frequently taught to general practitioners ( GPs ) as a structured consultation that provides a psychological explanation for medically unexplained symptoms . AIMS To determine if practice -based training of GPs in reattribution changes doctor-patient communication , thereby improving outcomes in patients with medically unexplained symptoms of 3 months ' duration . METHOD Cluster r and omised controlled trial in 16 practice s , 74 GPs and 141 patients with medically unexplained symptoms of 6 hours of reattribution training v. treatment as usual . RESULTS With training , the proportion of consultations mostly consistent with reattribution increased ( 31 v. 2 % , P=0.002 ) . Training was associated with decreased quality of life ( health thermometer difference -0.9 , 95 % CI -1.6 to -0.1 ; P=0.027 ) with no other effects on patient outcome or health contacts . CONCLUSIONS Practice -based training in reattribution changed doctor-patient communication without improving outcome of patients with medically unexplained symptoms The objective of this research was to identify determinants of the magnitude of intracluster correlation coefficients ( ICCs ) in cluster r and omized trials from the field of implementation research . A survey of experts was conducted to generate a priori hypotheses of factors that might affect ICC size . Hypotheses were tested on empirical estimates of ICCs calculated from 21 implementation research data sets , mainly from the UK . Effects of setting ( primary or secondary care ) , type of variable ( process or outcome ) , type of measurement ( objective or subjective ) , prevalence of outcome and size of cluster were tested . In total , 220 ICCs were available ( range 0 to 0.415 ) . Significant differences in ICC magnitude were found . The ICCs were significantly higher for process than for outcome variables , and for secondary care outcomes compared with primary care outcomes . The effects of prevalence and size were less clear cut . There was no evidence to suggest that type of measurement affected ICC size . In conclusion , accurate estimates of ICCs are essential for sample size calculations for cluster r and omized trials of professional behaviour change interventions . This study demonstrates that ICCs are sensitive to a number of trial factors , particularly setting and outcome type . These factors must be considered when planning such cluster r and omized trials BACKGROUND Emotional disorder associated with physical illness falls into two main groups : psychological reaction to physical illness and somatic presentation of psychological disorder Psychological treatments are becoming more widespread in the general hospital setting , but there are few systematic evaluations . METHOD A manual and computer ( MEDLINE ) literature search was performed . Studies which provided insight into clinical practice were selected for discussion , and r and omised controlled trials of at least 6 weeks duration and inclusion of 30 or more subjects were selected for review . RESULTS Fourteen empirical studies were found : six involving patients with chronic organic disorder and eight involving patients with somatisation . CONCLUSIONS There is little empirical evidence that psychotherapeutic interventions are of benefit when applied indiscriminately to patients with organic disease . Further work is required to delineate subgroups of patients who may be responsive . There is mounting evidence that psychotherapy is beneficial in patients with somatisation disorders . Patients with very chronic symptoms may require intensive treatment approaches PURPOSE Patients seeking care for medically unexplained physical symptoms pose a major challenge at primary care sites , and there are very few well-accepted and properly evaluated interventions to manage such patients . METHODS We tested the effectiveness of a cognitive behavior therapy (CBT)-type intervention delivered in primary care for patients with medically unexplained physical symptoms . Patients were r and omly assigned to receive either the intervention plus a consultation letter or usual clinical care plus a consultation letter . Physical and psychiatric symptoms were assessed at baseline , at the end of treatment , and at a 6-month follow-up . All treatments and assessment s took place at the same primary care clinic where patients sought care . RESULTS A significantly greater proportion of patients in the intervention group had physical symptoms rated by clinicians as “ very much improved ” or “ much improved ” compared with those in the usual care group ( 60 % vs 25.8 % ; odds ratio = 4.1 ; 95 % confidence interval , 1.9–8.8 ; P<.001 ) . The intervention ’s effect on unexplained physical symptoms was greatest at treatment completion , led to relief of symptoms in more than one-half of the patients , and persisted months after the intervention , although its effectiveness gradually diminished . The intervention also led to significant improvements in patient-reported levels of physical symptoms , patient-rated severity of physical symptoms , and clinician-rated depression , but these effects were no longer noticeable at follow-up . CONCLUSIONS This time-limited , CBT-type intervention significantly ameliorated unexplained physical complaints of patients seen in primary care and offers an alternative for managing these common and problematic complaints in primary care setting OBJECTIVE To assess changes in health related quality of life after a cognitive behavioural program for patients diagnosed with abridged somatization disorder in primary care . METHOD A multicentre , r and omized , parallel group , controlled trial was design ed . 168 patients were recruited from 29 primary health care centres in Spain and were r and omly assigned to one of the three study arms : treatment as usual improved with Smith 's norms , individual cognitive behavioural treatment , and group cognitive behavioural treatment . Health-related quality of life was assessed using SF-36 Health Survey . RESULTS Individual cognitive behavioural treatment achieves greater changes in health related quality of life than group cognitive behavioural therapy and treatment as usual . Improvement in health related quality of life was fully observed at 12 month , and partially at 6 months . The modality of intervention interacts with time in all dimensions except for Physical functioning and Vitality . Patients who received individual cognitive behavioural therapy treatment had better scores in Physical and Mental health summary measures at 12 month follow-up . CONCLUSIONS Individual cognitive behavioural treatment is the most effective way to improve health related quality of life in abridged somatization disorder patients , and its effects are sustained over time . Also , regardless of the type of intervention , physical functioning improves compared with treatment as usual Background : Patients with medically unexplained or functional somatic symptoms ( FSS ) are prevalent in primary care . In this pragmatic cluster-r and omised controlled trial we aim ed to test the effect of a training programme ( The Extended Reattribution and Management model ) for general practitioners ( GPs ) in the treatment of FSS . Methods : 38 participating GPs were r and omised to the control group or the training group . The GPs included consecutive 18- to 65-year-old patients presenting during a 3-week period for new health complaints . We assessed a stratified sub sample with the psychiatric interview Schedules of Clinical Assessment in Neuropsychiatry . Of 701 patients interviewed , 350 fulfilled the diagnostic criteria for any ICD-10 somatoform disorder ( SD ) and 111 presented FSS without fulfilling these criteria ( sub-threshold SD ) . Patients completed question naires at baseline and after 3 , 12 and 24 months . The question naires included assessment of health status ( 36-item Medical Outcomes Study Short Form ; SF-36 ) , health anxiety ( Whiteley-7 ) and physical symptoms ( Symptom Check List-90 , somatization subscale ) . Results : Patients with SD consulting trained GPs improved more on our primary outcome of physical functioning than patients consulting control GPs at the 3-month follow-up ( p = 0.004 ) , but the improvement was not statistically significant at later follow-up . We found no significant differences in improvement between patients with SD and those with sub-threshold SD . Results for other SF-36 subscales , physical symptoms and health anxiety only showed statistically significant differences between the intervention and control groups for patients with SD ; patients consulting trained GPs had less improvement in vitality , health anxiety and physical symptoms at 24 months compared with the control group . Conclusions : GP training may accelerate improvement in physical functioning for patients with SD . However , the effect is small and may not be clinical ly significant OBJECTIVE The objective of this study was to compare the effects of psychosocial interventions based on the modified reattribution model for somatizing patients in general practice ( GP ) with those of nonspecific psychosocial primary care ( PPC ) alone . METHODS Forty-two GPs were r and omized , 23 into the intervention group ( IG ) , who were trained in reattribution techniques , and 19 into the control group ( CG ) . One hundred twenty-seven patients were included . Primary outcome measures were somatoform symptoms and quality of life . RESULTS Multilevel modeling revealed a reduction of physical symptoms ( P = .007 ) , an improvement in physical functioning ( P = .0172 ) , and a reduction of depression ( P = .0211 ) and anxiety ( P = .0388 ) in the IG compared with the CG at the 3-month follow-up . However , results no longer remained significant after controlling for baseline and covariate variables besides a reduction of physical symptoms at 6-month follow-up ( P = .029 ) . CONCLUSION Compared with nonspecific PPC , the effects of reattribution techniques were small and limited to physical symptoms CONTEXT Few depressed older adults receive effective treatment in primary care setting s. OBJECTIVE To determine the effectiveness of the Improving Mood-Promoting Access to Collaborative Treatment ( IMPACT ) collaborative care management program for late-life depression . DESIGN R and omized controlled trial with recruitment from July 1999 to August 2001 . SETTING Eighteen primary care clinics from 8 health care organizations in 5 states . PARTICIPANTS A total of 1801 patients aged 60 years or older with major depression ( 17 % ) , dysthymic disorder ( 30 % ) , or both ( 53 % ) . INTERVENTION Patients were r and omly assigned to the IMPACT intervention ( n = 906 ) or to usual care ( n = 895 ) . Intervention patients had access for up to 12 months to a depression care manager who was supervised by a psychiatrist and a primary care expert and who offered education , care management , and support of antidepressant management by the patient 's primary care physician or a brief psychotherapy for depression , Problem Solving Treatment in Primary Care . MAIN OUTCOME MEASURES Assessment s at baseline and at 3 , 6 , and 12 months for depression , depression treatments , satisfaction with care , functional impairment , and quality of life . RESULTS At 12 months , 45 % of intervention patients had a 50 % or greater reduction in depressive symptoms from baseline compared with 19 % of usual care participants ( odds ratio [ OR ] , 3.45 ; 95 % confidence interval [ CI ] , 2.71 - 4.38 ; P<.001 ) . Intervention patients also experienced greater rates of depression treatment ( OR , 2.98 ; 95 % CI , 2.34 - 3.79 ; P<.001 ) , more satisfaction with depression care ( OR , 3.38 ; 95 % CI , 2.66 - 4.30 ; P<.001 ) , lower depression severity ( range , 0 - 4 ; between-group difference , -0.4 ; 95 % CI , -0.46 to -0.33 ; P<.001 ) , less functional impairment ( range , 0 - 10 ; between-group difference , -0.91 ; 95 % CI , -1.19 to -0.64 ; P<.001 ) , and greater quality of life ( range , 0 - 10 ; between-group difference , 0.56 ; 95 % CI , 0.32 - 0.79 ; P<.001 ) than participants assigned to the usual care group . CONCLUSION The IMPACT collaborative care model appears to be feasible and significantly more effective than usual care for depression in a wide range of primary care practice OBJECTIVE The aim of this study was to examine whether bioenergetic exercises ( BE ) significantly influence the inpatient psychotherapeutic treatment results for Turkish immigrants with chronic somatoform disorders . METHOD In a 6-week r and omized , prospect i ve , controlled trial , we treated a sample of 128 Turkish patients : 64 were r and omly assigned to BE and 64 participated in gymnastic exercises in lieu of BE . The Symptom Checklist ( SCL-90-R ) and State-Trait Anger Expression Inventory ( STAXI ) were employed . RESULTS According to the intent-to-treat principle , the bioenergetic analysis group achieved significantly better treatment results on most of the SCL-90-R and STAXI scales . CONCLUSIONS BE appears to improve symptoms of somatization , social insecurity , depressiveness , anxiety , and hostility in the inpatient therapy of subjects with chronic somatoform disorders . Reduction of the anger level and reduction in directing anger inwards , with a simultaneous increase of spontaneous outward emotional expression , could be expected Abstract Objective : To test whether a disclosure intervention improves subjective health and reduces medical consumption and sick leave in somatising patients in general practice . Design : Non-blind r and omised controlled trial . Setting : 10 general practice s in the Netherl and s. Participants : 161 patients who frequently attended general practice with somatising symptoms . Intervention : Patients in the intervention group were visited two to three times and invited to disclose emotionally important events in their life . Control patients received normal care from their general practitioners . Main outcome measures : Use of medical services ( drugs and healthcare visits ) , subjective health , and sick leave assessed by self completion question naires after 6 , 12 , and 24 months . Results : Of the 161 patients , 137 completed the trial ( 85 % ) . Both groups were comparable at baseline . The intervention had no effect on the main outcome measures at any point . Intervention patients made one more visit to health care ( 95 % confidence interval −4 to 6 ) ; the use of medicines did not change in both groups ( −1 to 1 ) ; subjective health improved 3.6 points more in the control group ( −11.2 to 4.3 ) ; and disclosure patients were on sick leave one more week ( −1 to 3 ) . Patients often had a depression or anxiety disorder for which they were not receiving adequate care . Conclusion : Although the intervention was well received by patients and doctors , disclosure had no effect on the health of somatising patients in general practice . What is already known on this topic Up to 5 % of patients in general practice attend frequently with somatising symptoms Emotional expression techniques have been shown to have favourable effects on subjective health , visits to the doctor , and symptoms in healthy people What this study adds A disclosure intervention does not improve somatisation in primary care About 45 % of patients had an anxiety or depressive disorder , which was often Background Medically unexplained symptoms are an important mental health problem in primary care and generate a high cost in health services . Cognitive behavioral therapy and psychodynamic therapy have proven effective in these patients . However , there are few studies on the effectiveness of psychosocial interventions by primary health care . The project aims to determine whether a cognitive-behavioral group intervention in patients with medically unexplained symptoms , is more effective than routine clinical practice to improve the quality of life measured by the SF-12 question ary at 12 month . Methods / design This study involves a community based cluster r and omized trial in primary healthcare centres in Madrid ( Spain ) . The number of patients required is 242 ( 121 in each arm ) , all between 18 and 65 of age with medically unexplained symptoms that had seeked medical attention in primary care at least 10 times during the previous year . The main outcome variable is the quality of life measured by the SF-12 question naire on Mental Healthcare . Secondary outcome variables include number of consultations , number of drug ( prescriptions ) and number of days of sick leave together with other prognosis and descriptive variables . Main effectiveness will be analyzed by comparing the percentage of patients that improve at least 4 points on the SF-12 question naire between intervention and control groups at 12 months . All statistical tests will be performed with intention to treat . Logistic regression with r and om effects will be used to adjust for prognostic factors . Confounding factors or factors that might alter the effect recorded will be taken into account in this analysis . Discussion This study aims to provide more insight to address medically unexplained symptoms , highly prevalent in primary care , from a quantitative methodology . It involves intervention group conducted by previously trained nursing staff to diminish the progression to the chronicity of the symptoms , improve quality of life , and reduce frequency of medical consultations . Trial registration The trial was registered with Clinical Trials.gov , number NCT01484223 [ http:// Clinical Trials.gov ] CONTEXT Functional relaxation is based on concentration on body perception while moving the joints of the skeleton smoothly and simultaneously breathing out . Case reports have shown that patients with headaches can profit from functional relaxation . OBJECTIVE To examine whether patients with chronic tension headaches ( International Headache Society diagnosis ) who use functional relaxation as a complementary treatment will report less pain than before they learned this technique . DESIGN R and omized , prospect i ve , single-blind , controlled trial . St and ardized elements of functional relaxation were compared to a placebo-relaxation technique , a simple isotomic exercise of the h and . SETTING Primary care , ambulatory private practice . PARTICIPANTS Twelve matched pairs were chosen according to age , sex , and initial pain intensity . This poststratification was performed on patients , who kept a complete pain diary covering 60 days before and 60 days after the introduction to the therapy . After a 45-minute introduction in small groups , the patients were told to do the exercises as often as possible for the following 2 months . MAIN OUTCOME MEASURES Pain diary . RESULTS In the functional-relaxation group , a significant reduction was found in the sum of total pain hours and in high- and medium-intensive pain ( Wilcoxon signed rank test ) . CONCLUSIONS This study supports the concept that this psychosomatic therapy can bring relief from tension headaches . This procedure can be viewed as an easy-to-learn relaxation technique to be used either prophylactic or complementary to pharmaceutical treatment OBJECTIVE ( a ) To evaluate the effect of a cognitive-behavioural inpatient treatment and ( b ) to analyse the differential efficacy of an additional ( " soma " ) group management training of somatisation . METHODS The final sample consisted of 191 patients with somatisation syndrome ( patients with at least eight DSM-IV somatoform symptoms ) . Patients were r and omly assigned to ( I ) " st and ard treatment + soma " or ( II ) " st and ard treatment + relaxation training . " A waiting control group consisted of 34 patients . All patients were diagnosed with a structured clinical interview for DSM-IV and received an interview on medical consulting behaviour and question naires concerning somatoform symptoms , general psychopathology , subjective health status , and life satisfaction . RESULTS Results show high impairment of the sample prior to treatment . At the 1-year follow-up , all outcome criteria were significantly reduced . The differential effect of the additional soma treatment was significant only for a reduction of visits to the doctor . Greatest longitudinal effect sizes were found for the reduction of somatoform symptoms . CONCLUSION Considering the subjects ' high initial impairment , the outcome results are encouraging . The specific effect on health care use highlights the socioeconomic relevance BACKGROUND Many specialty-specific functional somatic syndrome diagnoses exist to describe people who are experiencing so-called medically unexplained symptoms . Although cognitive-behavioural therapy can be effective in the management of such syndromes , it is rarely available . A cognitive-behavioural therapy suitable for group treatment of people with different functional somatic syndromes could address this problem . AIMS To test the efficacy of a cognitive-behavioural therapy ( Specialised Treatment for Severe Bodily Distress Syndromes , STreSS ) design ed for patients with a range of severe functional somatic syndromes . METHOD A r and omised controlled trial ( clinical trials.gov , NCT00132197 ) compared STreSS ( nine 3.5 h sessions over 4 months , n = 54 ) with enhanced usual care ( management by primary care physician or medical specialist , n = 66 ) . The primary outcome was improvement in aggregate score on subscales of the 36-item Short Form Health Survey ( physical functioning , bodily pain and vitality ) at 16 months . RESULTS Participants receiving STreSS had a greater improvement on the primary outcome ( adjusted mean difference 4.0 , 95 % CI 1.4 - 6.6 , P = 0.002 ) and on most secondary outcomes . CONCLUSIONS In the management of functional somatic syndromes , a cognitive-behavioural group treatment was more effective than enhanced usual care BACKGROUND We hypothesized that somatizing patients managed by primary care physicians ( PCP ) would improve with a relationship-based intervention . METHODS We r and omized 30 adults with medically unexplained symptoms to treatment or usual care . Four PCPs were trained to intervene with cognitive-behavioral , pharmacological , and patient-centered management and deployed the intervention with seven scheduled visits over 12 months . Outcomes obtained at baseline and 12 months were : Mental component summary ( MCS ) , the primary endpoint , and measures of physical and psychological symptoms and of satisfaction with the PCP . RESULTS Patients averaged 52.5 years ; 83.3 % were female ; 79.6 % were black . Using a difference of differences approach , we found that the intervention produced a large effect size ( ES ) ( 0.82 ; CI : 0.08 to 1.57 ) for the MCS in the predicted direction , similar to the ES for physical ( −0.80 ; CI : −1.55 to −0.04 ) and psychological ( −1.06 ; CI : −1.83 to −0.28 ) improvement and for increased satisfaction with the PCP ( 0.94 ; CI : 0.15 to 1.74 ) . Using ANCOVA in a sensitivity analysis , we found that the ES fell slightly ( 0.59 ) , while other measures were unchanged . CONCLUSIONS Moderate-large effect sizes support the hypothesis that PCPs can effectively treat somatization . This points to the importance of performing a full RCT Background : Patients with medically unexplained symptoms make heavy dem and s on the health care system . An offer for psychological treatment is often declined . There is a need for acceptable and effective treatments . We assessed the acceptability and effectiveness of mindfulness-based cognitive therapy ( MBCT ) for patients with persistent medically unexplained symptoms . Method : A r and omized controlled trial comparing MBCT ( n = 64 ) to enhanced usual care ( EUC ; n = 61 ) . Participants were the 10 % most frequently attending patients in primary care . The primary outcome measure was general health status at the end of treatment . Secondary outcome measures were mental and physical functioning . Assessment s took place at the end of treatment and at the 9-month follow-up . Results : Health status and physical functioning did not significantly differ between groups . However , participants in the MBCT group reported a significantly greater improvement in mental functioning at the end of treatment ( adjusted mean difference , 3.9 ; 95 % CI , 0.24 - 7.6 ) , in particular with regard to vitality and social functioning . In addition , at 9 months of follow-up , the mindfulness skills ‘ observing ' and ‘ describing ' were significantly higher in the MBCT group . Within the MBCT group , almost half of the outcome measures had significantly improved at the end of treatment , whereas in the EUC group none had . Conclusions : MBCT was feasible for frequently attending patients with persistent medically unexplained symptoms in primary care . Although MBCT did not lead to a significant difference in general health status between the two groups , it did result in a significant improvement in mental functioning Background Anxiety , Depression and Somatoform ( ADSom ) disorders are highly prevalent in primary care . Managing these disorders is time-consuming and requires strong commitment on behalf of the General Practitioners ( GPs ) . Furthermore , the management of these patients is restricted by the high patient turnover rates in primary care practice s , especially in the German health care system . In order to address this problem , we implement a complex , low-threshold intervention by an Advanced Practice Nurse ( APN ) using a mixture of case management and counseling techniques to promote self-management in these patients . Here we present the protocol of the “ Self-Management Support for Anxiety , Depression and Somatoform Disorders in Primary Care ” (SMADS)- Study . Methods / Design The study is design ed as a cluster-r and omized controlled trial , comparing an intervention and a control group of 10 primary care practice s in each case . We will compare the effectiveness of the intervention applied by an APN with usual GP-care . A total of 340 participants will be enrolled in the study , 170 in either arm . We use the Patient Health Question naire-German version ( PHQ-D ) as a screening tool for psychiatric symptoms , including patients with a score above 5 on any of the three symptom scales . The primary outcome is self-efficacy , measured by the General Self-Efficacy Scale ( GSE ) , here used as a proxy for self-management . As secondary outcomes we include the PHQ-D symptom load and question naires regarding coping with illness and health related quality of life . Outcome assessment s will be applied 8 weeks and 12 months after the baseline assessment . Discussion The SMADS- study evaluates a complex , low threshold intervention for ambulatory patients presenting ADSom-symptoms , empowering them to better manage their condition , as well as improving their motivation to engage in self-help and health-seeking behaviour . The benefit of the intervention will be substantiated , when patients can enhance their expected self-efficacy , reduce their symptom load and engage in more self-help activities to deal with their everyday lives . After successfully evaluating this psychosocial intervention , a new health care model for the management of symptoms of anxiety , depression and somatoform disorders for ambulatory patients could emerge , supplementing the work of the GP.Trial registration Clinical trials.gov Identifier : Objectives To conduct a pilot trial of a primary care Symptoms Clinic for patients with medically unexplained symptoms and evaluate recruitment and retention , and acceptability of the intervention and to estimate potential treatment effects for a full trial . Trial design R and omised parallel group pilot trial . Setting Primary care in one locality . Participants Primary care data base and postal question naire were used to identify patients with multiple specialist referrals and multiple physical symptoms unlikely to be explained by disease . Interventions General practitioner ( GP ) with special interest ‘ Symptoms Clinic ’ + usual care versus usual care alone . The Symptoms Clinic comprised one long ( 1 h ) and three short ( 20 min ) appointments . Outcomes Number of patients identified and recruited ; acceptability of the intervention ( items from Client Satisfaction Question naire and interview ) ; Medical Outcomes Survey Short Form 12 ( SF-12 ) physical component summary . R and omisation Automated blocked r and omisation accessed by telephone . Blinding None . Numbers r and omized 16 to intervention and 16 to usual care alone . Recruitment 72 patients , from seven GP practice s , had repeated specialist referrals and a Patient Health Question naire (PHQ)-15 score of ≥10 indicating a high probability of medically unexplained symptoms . 15 were ineligible and 25 declined to participate . Numbers analysed 26 patients ; two patients r and omised to the intervention group were incorrectly included , three patients in the intervention group and one control did not complete outcome measures . Outcome Most patients r and omised to the Symptoms Clinic found the intervention acceptable : eight out of 11 reported the intervention helped them to deal with their problems . The mean difference between groups in SF-12 physical component summary , adjusted for baseline , was 3.8 points ( SD 6 ) . Harms No observed harms . Conclusions Patients with multiple medically unexplained symptoms can be systematic ally identified in primary care ; a r and omised trial comparing the Symptoms Clinic with usual care is feasible and has the potential to show clinical ly meaningful benefit . Trial registration IS RCT N63083469 Background A brief psychodynamic interpersonal therapy ( PIT ) in patients with multisomatoform disorder has been recently shown to improve health-related quality of life . Aims To assess cost-effectiveness of PIT compared to enhanced medical care in patients with multisomatoform disorder . Method An economic evaluation alongside a r and omised controlled trial ( International St and ard R and omised Controlled Trial Number IS RCT N23215121 ) conducted in 6 German academic outpatient centres was performed . Incremental cost-effectiveness ratio ( ICER ) was calculated from the statutory health insurance perspective on the basis of quality adjusted life years ( QALYs ) gained at 12 months . Uncertainty surrounding the cost-effectiveness of PIT was presented by means of a cost-effectiveness acceptability curve . Results Based on the complete-case analysis ICER was 41840 Euro per QALY . The results did not change greatly with the use of multiple imputation ( ICER = 44222 ) and last observation carried forward ( LOCF ) approach to missing data ( ICER = 46663 ) . The probability of PIT being cost-effective exceeded 50 % for thresholds of willingness to pay over 35 thous and Euros per QALY . Conclusions Cost-effectiveness of PIT is highly uncertain for thresholds of willingness to pay under 35 thous and Euros per QALY Background : All therapists direct their attention in some manner during psychotherapy . A special form of directing attention , ‘ mindfulness ’ , is recommended . This study aim ed to examine whether , and to what extent , promoting mindfulness in psychotherapists in training ( PiT ) influences the treatment results of their patients . Methods : The therapeutic course and treatment results of 124 in patients , who were treated for 9 weeks by 18 PiTs , were compared . The PiTs were r and omly assigned to 1 of 2 groups : ( i ) those practicing Zen meditation ( MED ; n = 9 or ( ii ) control group , which did not perform meditation ( noMED ; n = 9 ) . The results of treatment ( according to the intent-to-treat principle ) were examined using the Session Question naire for General and Differen-tial Individual Psychotherapy ( STEP ) , the Question naire of Changes in Experience and Behavior ( VEV ) and the Symptom Checklist ( SCL-90-R ) . Results : Compared to the noMED group ( n = 61 ) , the patients of PiTs from the MED group ( n = 63 ) had significantly higher evaluations ( according to the intent-to-treat principle ) for individual therapy on 2 STEP scales , clarification and problem-solving perspectives . Their evaluations were also significantly higher for the entire therapeutic result on the VEV . Furthermore , the MED group showed greater symptom reduction than the noMED group on the Global Severity Index and 8 SCL-90-R scales , including Somatization , Insecurity in Social Contact , Obsessiveness , Anxiety , Anger/Hostility , Phobic Anxiety , Paranoid Thinking and Psychoticism . Conclusions : This study indicates that promoting mindfulness in PiTs could positively influence the therapeutic course and treatment results in their patients The aim of this study was to determine whether grade d activity restored occupational function in industrial blue-collar workers who were sick-listed for 8 weeks because of subacute , nonspecific , mechanical low back pain ( LBP ) . Patients with LBP , who had been examined by an orthopedic surgeon and a social worker , were r and omly assigned to either an activity group ( n = 51 ) or a control group ( n = 52 ) . Patients with defined orthopedic , medical , or psychiatric diagnoses were excluded before r and omization . The grade d activity program consisted of four parts : ( 1 ) measurements of functional capacity ; ( 2 ) a work-place visit ; ( 3 ) back school education ; and ( 4 ) an individual , submaximal , gradually increased exercise program , with an operant-conditioning behavioral approach , based on the results of the tests and the dem and s of the patient 's work . Records of the amount of sick leave taken over a 3-year period ( ie , the 1-year periods before , during , and after intervention ) were obtained from each patient 's Social Insurance Office . The patients in the activity group returned to work significantly earlier than did the patients in the control group . The median number of physical therapist appointments before return to work was 5 , and the average number of appointments was 10.7 ( SD = 12.3 ) . The average duration of sick leave attributable to LBP during the second follow-up year was 12.1 weeks ( SD = 18.4 ) in the activity group and 19.6 weeks ( SD = 20.7 ) in the control group . Four patients in the control group and 1 patient in the activity group received permanent disability pensions . The grade d activity program made the patients occupationally functional again , as measured by return to work and significantly reduced long-term sick leave This r and omized , prospect i ve study investigated the effectiveness of two group behavioral medicine interventions for primary care patients experiencing physical symptoms with a psychosocial component ( eg , palpitations , gastrointestinal disturbances , headaches , malaise , sleep disorders ) . The subjects were 80 volunteers at a health maintenance organization ( HMO ) in the greater Boston area . Both interventions focused on the mind/body relationship and used didactic material , relaxation-response training , awareness training , and cognitive restructuring . The two behavioral medicine intervention groups were compared with a group that focused exclusively on information about stress management and its relation to illness . Measures of visits to the HMO and of distress from physical and psychological symptoms were obtained before the interventions and again 6 months afterward . At the 6-month follow-up , patients in the behavioral medicine groups showed significantly greater reductions in visits to the HMO and in discomfort from physical and psychological symptoms than did the patients in the information group . The results suggest that when the relationship among thoughts and behaviors and symptoms of patients with psychosomatic dysfunction is actively addressed , the patients ' discomfort level and the cost of medical care can be reduced A large proportion of patients present to primary care with chronic , stress-related symptoms having no organic cause . Biomedical treatment of these patients is usually ineffective and expensive . A 6-week behavioral medicine intervention design ed to provide adjunctive treatment to primary care was evaluated in a r and omized , controlled study . Thirty-eight individuals receiving treatment and 44 waiting for treatment completed the SCL-90-R at times corresponding to 1 week before ( time 1 ) and 1 week after the course ( time 2 ) . The treatment group was then followed up at 6 months . After correction for initial levels , the treatment group reported significantly less somatization , anxiety , and depression than did the wait-list group at time 2 . Within the treatment group , decreases in somatization , anxiety , and depression were statistically significant and were maintained 6 months later . Within the wait-list group , distress remained unchanged . A review of relevant literature reveals that a general behavioral medicine course such as the one studied here has an important adjunctive role in primary care , since 1 ) subsyndromal psychological distress is common in primary care ; 2 ) physicians are reluctant to address psychosocial issues ; 3 ) negative mood is associated with poor health ; 4 ) negative mood is associated with high , inappropriate medical utilization ; and 5 ) negative mood is associated with help-seeking behavior Abstract OBJECTIVE : There is no proven primary care treatment for patients with medically unexplained symptoms ( MUS ) . We hypothesized that a long-term , multidimensional intervention by primary care providers would improve MUS patients ’ mental health . DESIGN : Clinical trial . SETTING : HMO in Lansing , MI . PARTICIPANTS : Patients from 18 to 65 years old with 2 consecutive years of high utilization were identified as having MUS by a reliable chart rating procedure ; 206 subjects were r and omized and 200 completed the study . INTERVENTION : From May 2000 to January 2003 , 4 primary care clinicians deployed a 12-month intervention consisting of cognitive-behavioral , pharmacological , and other treatment modalities . A behaviorally defined patient-centered method was used by clinicians to facilitate this treatment and the provider-patient relationship . MAIN OUTCOME MEASURE : The primary endpoint was an improvement from baseline to 12 months of 4 or more points on the Mental Component Summary of the SF-36 . RESULTS : Two hundred patients averaged 13.6 visits for the year preceding study . The average age was 47.7 years and 79.1 % were females . Using intent to treat , 48 treatment and 34 control patients improved ( odds ratio [OR]=1.92 , 95 % confidence interval [ CI ] : 1.08 to 3.40 ; P=.02 ) . The relative benefit ( relative “ risk ” for improving ) was 1.47 ( CI : 1.05 to 2.07 ) , and the number needed to treat was 6.4 ( 95 % CI : 0.89 to 11.89 ) . The following baseline measures predicted improvement : severe mental dysfunction ( P<.001 ) , severe body pain ( P=.039 ) , nonsevere physical dysfunction ( P=.003 ) , and at least 16 years of education ( P=.022 ) ; c-statistic=0.75 . CONCLUSION : The first multidimensional intervention by primary care clinicians led to clinical ly significant improvement in MUS patients ABSTRACT BACKGROUND Somatization and hypochondriacal health anxiety are common sources of distress , impairment , and costly medical utilization in primary care practice . A range of interventions is needed to improve the care of these patients . OBJECTIVE To determine the effectiveness of two cognitive behavioral interventions for high-utilizing , somatizing patients , using the re sources found in a routine care setting . DESIGN Patients were r and omly assigned to a two-step cognitive behavioral treatment program accompanied by a training seminar for their primary care physicians , or to relaxation training . Providers routinely working in these patients ’ primary care practice s delivered the cognitive behavior therapy and relaxation training . A follow-up assessment was completed immediately prior to treatment and 6 and 12 months later . SUBJECTSEighty-nine medical out patients with elevated levels of somatization , hypochondriacal health anxiety , and medical care utilization . MEASUREMENTS Somatization and hypochondriasis , overall psychiatric distress , and role impairment were assessed with well-vali date d , self-report question naires . Outpatient visits and medical care costs before and after the intervention were obtained from the encounter cl aims data base . RESULTS At 6 month and 12 month follow-up , both intervention groups showed significant improvements in somatization ( p < 0.01 ) , hypochondriacal symptoms ( p < 0.01 ) , overall psychiatric distress ( p < 0.01 ) , and role impairment ( p < 0.01 ) . Outcomes did not differ significantly between the two groups . When both groups were combined , ambulatory visits declined from 10.3 to 8.8 ( p = 0.036 ) , and mean ambulatory costs decreased from $ 3,574 to $ 2,991 ( p = 0.028 ) in the year preceding versus the year following the interventions . Psychiatric visits and costs were unchanged . CONCLUSIONS Two similar cognitive behavioral interventions , delivered with the re sources available in routine primary care , improved somatization , hypochondriacal symptoms , overall psychiatric distress , and role function . They also reduced the ambulatory visits and costs of these high utilizing out patients BACKGROUND The evidence for the effectiveness of reattribution training are limited , and optimal service delivery is not yet established . OBJECTIVES The objectives of this study were to establish the feasibility and to optimize the service delivery and design of a definitive r and omized controlled trial ( RCT ) of reattribution training for patients with medically unexplained symptoms ( MUSs ) in routine primary care . METHODOLOGY The study was of a cluster RCT design with the practice as the unit of r and omization . Health facilitator (HF)-delivered reattribution training was compared with no reattribution training . The primary outcome measure used is doctor-patient communication in the consultation . Quantitative and qualitative methods identify barriers to effectiveness . The acceptability and feasibility of the intervention were established by attendance rates and postal survey after completion of training . RESULTS Sixteen practice s and 70 family practitioners ( FPs ) were recruited with representative practice and FP characteristics . Six hours of HF reattribution training to FPs in the workplace proved feasible and acceptable with all 35 FPs completing the training . Feedback from 27 ( 77 % ) FPs who received training indicated that 25 ( 93 % ) FPs believed that specific and relevant learning achievements were made , 22 ( 82 % ) felt more confident and 21 ( 77 % ) thought the training was useful . CONCLUSION HF-delivered reattribution training to whole practice s is feasible and acceptable , and its effectiveness is measurable in routine primary care We sought to determine the cost-efficiency of a brief family intervention program for patients with somatoform disorder . Two hundred fifty-six somatoform patients from 7 centers of primary care in Chile were r and omly assigned to either brief family intervention ( BFI ) or treatment as usual . The experimental group presented a significant cost reduction ( p = .001 ) 6 months and 12 months after the intervention , with lower costs than the control group on all measured variables and no decrease in patient satisfaction . Our results suggest that BFI might be a cost-efficient way of meeting the needs of somatoform patients . Replications in other cultural context s and dismantling studies to identify the effective ingredients of BFI are recommended BACKGROUND Multisomatoform disorder is characterised by severe and disabling bodily symptoms , and pain is one of the most common and impairing of these . Furthermore , these bodily symptoms can not be explained by an underlying organic disorder . Patients with multisomatoform disorder are commonly found at all levels of healthcare and are typically difficult to treat for physicians as well as for mental health specialists . AIMS To test whether brief psychodynamic interpersonal therapy ( PIT ) effectively improves the physical quality of life in patients who have had multisomatoform disorder for at least 2 years . METHOD We recruited 211 patients ( from six German academic outpatient centres ) who met the criteria for multisomatoform disorder for a r and omised , controlled , 12-week , parallelgroup trial from 1 July 2006 to 1 January 2009 ( International St and ard R and omised Controlled Trial Number IS RCT N23215121 ) . We r and omly assigned the patients to receive either 12 weekly sessions of PIT ( n = 107 ) or three sessions of enhanced medical care ( EMC , n = 104 ) . The physical component summary of the Short Form Health Survey ( SF-36 ) was the pre-specified primary outcome at a 9-month follow-up . RESULTS Psychodynamic interpersonal therapy improved patients ' physical quality of life at follow-up better than EMC ( mean improvement in SF-36 score : PIT 5.3 , EMC 2.2 ) , with a small to medium between-group effect size ( d = 0.42 , 95 % CI 0.15 - 0.69 , P = 0.001 ) . We also observed a significant improvement in somatisation but not in depression , health anxiety or healthcare utilisation . CONCLUSIONS This trial documents the long-term efficacy of brief PIT for improving the physical quality of life in patients with multiple , difficult-to-treat , medically unexplained symptoms OBJECTIVE The effectiveness of use of migrant health educators in the general practitioners ' care for female migrants with psychosomatic problems was evaluated to contribute to the improvement of the care for these patients . METHODS A r and omised controlled trial ( RCT ) design was used . A total of 104 patients ( 75 % ) agreed to take part in the intervention study . The patients were from Turkish and Moroccan immigrant groups living in The Netherl and s. The intervention group received counselling and education from the migrant health educators as adjuncts to the GPs ' care . Special attention was given to the patient 's cultural background , supporting the communication between GP and patient . The control group received regular treatment from their GPs . RESULTS A significant improvement of perceived general health , psychological health and reported ability to cope with pain was observed among the intervention group . No effects were found for social support and the perceived burden of stressful life-events . CONCLUSION The patients ' perceived health and coping abilities improved through the intervention as a whole . Not all outcome measures had been affected due to among others the diversity of physical and psychological complaints the patients suffered from , non-compliance and a perceived decrease of disability over time . PRACTICE IMPLICATION S The intervention methods should be integrated in the patient care delivery for migrants in general practice . Further development of intervention methods to address the patients ' social support is recommended OBJECTIVE The objective of the present study is to estimate the economic consequences of somatization disorder and functional somatic syndromes such as fibromyalgia and chronic fatigue syndrome , defined as bodily distress syndrome ( BDS ) , when mindfulness therapy is compared with enhanced treatment as usual . METHODS A total of 119 BDS patients were r and omized to mindfulness therapy or enhanced treatment as usual and compared with 5950 matched controls . Register data were analyzed from 10years before their inclusion to 15-month follow-up . The main outcome measures were disability pension at the 15-month follow-up and a reduction in total health care costs . Unemployment and sickness benefit prior to inclusion were tested as possible risk factors . RESULTS At 15-month follow-up , 25 % from the mindfulness therapy group received disability pension compared with 45 % from the specialized treatment group ( p=.025 ) . The total health care utilization was reduced over time in both groups from the year before inclusion ( mean $ 5325 , median $ 2971 ) to the year after inclusion ( mean $ 3644 , median $ 1593 ) ( p=.0001 ) . This overall decline was seen in spite of elevated costs due to assessment and mindfulness therapy or enhanced treatment as usual . The BDS patients accumulated significantly more weeks of unemployment and sickness benefit 5 and 10years before inclusion ( p<.0001 ) than the population controls . CONCLUSIONS Mindfulness therapy may prevent disability pension and it may have a potential to significantly reduce societal costs and increase the effectiveness of care . Accumulated weeks of unemployment and sickness benefit are possible risk factors for BDS OBJECTIVE The purpose of this prospect i ve study was to evaluate the effects of cognitive-behavioral treatment ( CBT ) on mental health status and healthcare utilization in patients with somatoform disorders ( SFD ) of a specialized tertiary care center . METHODS According to DSM-IV interviews , 54 patients had somatization disorder ( SD ) , 51 abridged somatization syndrome ( SSI-8 ) and 67 other defined SFD . A clinical non-SFD comparison group consisted of 123 patients . Treatment effects were controlled against the waiting list . Cost calculations for the 2-year periods before and after treatment were based on medical and billing records from health insurance companies . RESULTS The SFD patients improved significantly with respect to physical symptom distress , health anxieties , dysfunctional beliefs towards body and health , depression and psychosocial functioning . Their outpatient plus inpatient charges during the 2 years prior to treatment were about 2.2-fold higher than for average patients of the health system . At the 2-year follow-up , we found treatment-related cost offset of 382 ( -24.5 % ) for outpatient and 1098 ( -36.7 % ) for inpatient care . Indirect socioeconomic costs due to days lost from work decreased by 6702 ( -35.3 % ) . Per patient savings of 32,174 ( -63.9 % ) were found in a subgroup of somatizing high-utilizers . CONCLUSION The results encourage including treatment strategies to reduce somatoform illness behavior into clinical practice BACKGROUND The management of persistent , unexplained physical symptoms is challenging and often unsatisfactory for patients and doctors . Aerobic exercise training has benefited patients referred to secondary care with symptoms of chronic fatigue and fibromyalgia . It is not known if this approach is either possible or beneficial for patients with the broader range of persistent , unexplained symptoms found in primary care . OBJECTIVES To examine the feasibility and effects of aerobic exercise training in primary care patients with unexplained physical symptoms persisting more than 12 months . METHODS R and omized comparison ( n = 228 ) of aerobic exercise with stretching as control among patients recruited from primary care . Training comprised 20 , one-hour , sessions led by NHS physiotherapists . Adherence to training was recorded along with two groups of outcome measures : ( i ) documented symptoms and health care use , monitored from six months before to six months after training ; and ( ii ) self-reported measures including emotional state and perceived disability , assessed before , during and six months after training . RESULTS Exercise training proved feasible : more than 70 % of referred patients attended for assessment and were r and omized to aerobic or control exercise ; 78 % of eligible patients attended the first session ; and median attendance was 11 sessions for both programmes . Primary care consultations and prescriptions were significantly reduced in the 6 months after training ; extent of reduction was related to attendance at training sessions , irrespective of type . Whilst self-reported measures improved similarly during both training programmes , improvements were unrelated to level of attendance . CONCLUSION For primary care patients with persistent , unexplained physical symptoms willing to be involved in exercise training , aerobic exercise offers no benefits over non-aerobic exercise . Whilst the observed reduction in primary health care use following exercise training is potentially of practical importance in a group of patients characterized by high consultation rates , improvement in patients ' subjective state was not clearly attributable to exercise training Background : Treatment acceptance and motivation for psychotherapy of somatizing patients in the general hospital is low . Methods : Patients ( n = 91 ) fulfilling the criteria for somatization were r and omized into an intervention group ( n = 49 ) and a control group ( n = 42 ) . The patients in the intervention group attended 5 psychotherapeutic sessions based on the modified reattribution model . The patients in the control group received psychoeducational reading material . The primary outcomes were motivation for psychotherapy and contacting a psychotherapist after discharge . The secondary outcomes consisted of changes regarding somatoform symptoms , emotional distress and quality of life . Results : Patients from the intervention group were significantly more motivated for psychotherapy ( p = 0.001 ) than patients from the control group . At the 3-month follow-up , 42 % of the patients from the intervention group had contacted a psychotherapist , compared to 20 % of the patients from the control group ( p = 0.045 ) . At the 6-month follow-up , however , the ratio of patients having contacted a psychotherapist had changed to 44 and 29 % , respectively , and was no longer significant . The intensity of somatoform symptoms and the anxiety symptoms decreased and mental functioning improved significantly over time for patients from both groups . Conclusions : Short-term psychotherapeutic interventions for somatizing patients in general hospitals have a moderately better effect on motivation for psychotherapy and contacting a psychotherapist than psychoeducational reading material alone . Future studies should attempt to prove the effectiveness of short-term psychoeducational interventions for somatizing patients in the general hospital Purpose The objective of this study is to investigate the effect of a Self-Management Program for workers with a chronic disease . This program is based on the Chronic Disease Self-Management Program of Stanford University , modified for workers with a chronic somatic disease . Methods In a r and omized controlled trial , the effectiveness of a Self-Management Program was evaluated . Participants were r and omly assigned to the experimental group ( n = 57 ) and the control group ( n = 47 ) . The experimental group received an intervention , the control group received care as usual . Primary outcome measures were self-efficacy at work and the attitude towards self-management at work . Secondary outcomes were the SF-12 health survey question naire , job satisfaction and intention to change job . The results were measured at baseline , after the intervention and 8 months after the intervention . Results The attitude towards self-management at work ( enjoyment ) improved after 8 months for the intervention group ( p = 0.030 ) . No other outcome variable differed significantly . As an interaction effect , it was found that low educated workers developed a better physical health quality ( SF-12 ) in the intervention group compared with the control group . The attitude towards self-management at work ( importance ) improved in the intervention group for older and female workers and the attitude toward enjoying self-management at work improved for female workers only . Conclusion The results show that low educated workers , older workers and women benefit significantly more from the training than higher educated workers , younger workers and men Somatic symptoms , in the absence of clear disease progression or a psychiatric cause , are prevalent in older primary care patients ( 1 - 4 ) , and several studies ( 1 - 5 ) have identified psychological and psychosocial distress as prominent contributors to symptom manifestation in older and younger patients . Psychological interventions may be useful for reducing distress-driven symptoms in older primary care patients . The benefits of psychotherapy are numerous ( 6 ) , but psychotherapy can be re source intensive and costly and may be unnecessary for patients with distress-driven symptoms in the absence of a psychiatric disorder . For these patients , the use of written self-disclosure may reduce somatic symptoms , distress , and health care utilization . Written self-disclosure involves describing the thoughts and emotions associated with a distressing life experience . In experimental protocol s , people are asked to write about distressing experiences ( self-disclosure ) or trivial experiences ( control ) in a laboratory setting for 20 to 30 minutes on 3 consecutive days . Persons in the self-disclosure group are encouraged and to think about experiences involving relationships with others ( including parents , spouses , children , friends , or relatives ) and to think about how those experiences may have affected their past and may affect their present or future . To minimize experimental bias , detailed topics for writing are purpose ly not presented . The mechanism of action in written self-disclosure is largely theoretical and is believed to focus on the negative effect of inhibiting thoughts and emotions . People often inhibit negative thoughts and emotions associated with distressing events to keep them out of immediate awareness ( 7 ) . This process of inhibition can increase autonomic activity ( 8) , produce somatic symptoms , and diminish well-being ( 9 ) . The presence of somatic symptoms and decreased well-being often results in visits to a physician or other health care provider . Written self-disclosure may help a person to translate distressing thoughts and emotions into the written word and organize them within the context of a narrative . To the extent that the narrative is coherent and underst and able to the person doing the writing , that person gains a sense of control over the distressing thoughts and emotions . Consequently , the need to actively inhibit is diminished , and autonomic activity , somatic symptoms , and distress may be reduced . Written narratives need not be shared with or understood by other people for the benefits to occur . However , written narratives may help a person to share his or her experiences with others , and this may be beneficial . Research examining the content of writing sample s created during self-disclosure studies suggests that people who incorporate increasing numbers of causal words ( such as because and reason ) and insight words ( for example , underst and and realize ) into their description of the thoughts and emotions associated with a distressing experience benefit most from writing . In contrast , people who do not use causal and insight words or people whose initial written disclosure tells a coherent , resolved story are less likely to benefit from the process of writing ( 10 ) . Despite our limited empirical underst and ing of the mechanisms of written self-disclosure , the effect of this technique has been evaluated in numerous healthy population s over the past decade . Recent meta-analytic findings ( 11 ) support an overall moderate effect of written disclosure in healthy people with respect to a variety of somatic and psychological symptoms as well as health care utilization . Unfortunately , written self-disclosure has been evaluated primarily in healthy young adults in tightly controlled experimental setting s. It is not known whether this type of experimental protocol is feasible or effective as a primary carebased intervention for older patients . Therefore , we sought to develop a clinical intervention from an existing experimental protocol , evaluate the feasibility of using the intervention in primary care setting s , and describe initial outcomes . Methods Participants Patients were selected from a university-based geriatric primary care clinic and an internal medicine primary clinic in Birmingham , Alabama . Patients who met the eligibility criteria and agreed to participate in the study were r and omly assigned to the intervention group or the control group . Patients were included in the study if they were 66 years of age or older , did not have a current psychiatric diagnosis , had a Mini-Mental Status Examination ( 12 ) score of 24 or more or no diagnosis of dementia , had at least a fifth- grade education , could read the consent form without assistance , were physically able to write for 20 minutes on three occasions , and had transportation to and from the primary care clinics . A minimal distress level was not used as an inclusion criterion because of the difficulty in distinguishing between distress-driven and disease-driven somatic symptoms . The presence of a few somatic symptoms was not used as an inclusion criterion because previous studies showed the benefits of written self-disclosure in healthy population s ( 11 ) . Measurements Feasibility Outcomes Feasibility outcomes were patient recruitment and retention , total time required to deliver the intervention , personnel requirements , and patient and provider satisfaction . Satisfaction was assessed with an adaptation of the visit-specific satisfaction question naire ( 13 ) . Responses to nine items were evaluated on a Likert-type scale that ranged from 1 ( poor ) to 5 ( excellent ) . Clinical Outcomes Somatic and distress symptoms were assessed by using the Patient Health Question naire ( 14 ) . Diagnostic categories of this question naire include mood , anxiety , somatoform , and eating disorders , as well as alcohol abuse . We calculated a total distress score ( range , 0 to 74 ) by summing the frequency and severity of all items on the Patient Health Question naire except those in the Somatization Scale . The Somatization Scale was used to calculate a total somatic symptom score ( range , 0 to 26 ) . The Somatization Scale comprises 13 symptoms common in the primary care setting ( pain in the stomach , back , joints , head , or chest ; menstrual cramps ; pain during sexual intercourse ; dizziness ; fainting ; pounding heart ; shortness of breath ; and two categories of gastrointestinal problems [ nausea , gas , and indigestion ; constipation , loose bowels , and diarrhea ] ) . For both the somatic and distress scores , higher scores indicate more frequent and severe symptoms . Somatic and distress symptoms were assessed at baseline and 1 month after the intervention . Changes in scores from baseline to 1 month after the intervention were examined . We assessed health care utilization by using encounter data from a local managed care provider . Data were abstract ed 3 months before the intervention , during the intervention , and 3 months after the intervention . Total outpatient service use was defined as the number of Physicians ' Current Procedural Terminology codes for outpatient services for each time period . Total charges paid ( associated costs ) were defined as the total dollar amount paid by the insurance carrier . Changes in total outpatient service use and total charges paid from baseline to after the intervention were examined . Procedures To recruit patients , a checklist containing exclusion criteria ( psychiatric diagnosis , Mini-Mental Status Examination score < 24 , or dementia ) was placed on the outside of each chart and completed by the primary care provider . Patients suitable for the study were greeted by the project manager at the completion of the office visit . They were given a brief overview of the study , and the inclusion criteria were review ed . Before beginning the protocol , patients were escorted to a private office , where informed consent was obtained , and were r and omly assigned to a study group . In both groups , the first session included completion of baseline measures and the first writing sample . Writing instructions were read aloud to minimize the possibility of misunderst and ing . Briefly , patients in the treatment group were asked to write about the thoughts and feelings associated with the most distressing event of their lives . Patients in the control group were asked to write about what they did to stay healthy ( see Appendix ) . Appendix Figure . Patient recruitment and exclusion . To promote confidentiality and increase patients ' comfort with the disclosure of personal information , we informed patients that all writing sample s would be anonymous . Specifically , their names would not appear on the writing sample s and the sample s would not be shared with the patients ' physicians . Patients were asked not to share the content of their writing sample s with anyone during the intervention . Patients were told that each writing sample would be review ed briefly by the principal investigator solely for the purpose of checking that instructions had been followed in each group . It was emphasized to patients that the details of the content of the writing sample s would not be evaluated or analyzed . To avoid bias , anonymity and confidentiality were emphasized to patients in both groups . Patients were then left alone to complete their writing . Each patient wrote for 20 minutes . After the first writing session , patients scheduled two times in the next 2 weeks at which to complete the second and third writing sample s. Patients in both groups were given take-home instructions , paper for writing , and stamped envelopes in which to return their writing sample s. Patients were telephoned 5 minutes before their scheduled times to write . They were instructed to write alone in a quiet place for 20 minutes and , when finished , to mail the writing sample to the project manager . Both groups completed follow-up question naires approximately 1 month after their final writing sessions . Upon receipt of completed follow-up packets , patients OBJECTIVES To test the effect of psychological intervention on multiple medically unexplained physical symptoms , psychological symptoms , and health care utilization in addition to medical care as usual . To identify patient-related predictors of change in symptoms and care utilization . METHODS In a r and omized controlled trial , subjects were assigned to one of two conditions : psychological intervention by a qualified therapist plus care as usual by a general practitioner ( GP ) or care as usual only . Participants ( N=98 ) were administered a st and ardized interview and several outcome measures at intake and after 6 months and 12 months after intake . GPs rated medically unexplained and explained symptoms and consultations over a period of 1 1/2 years . RESULTS ANOVAs for repeated measures showed that self-reported and GP-registered unexplained physical symptoms decreased from pretest to posttest to follow-up . Psychological symptoms and consultations decreased from pretest to posttest . GP-registered explained symptoms did not decrease . However , intervention and control groups did not differ in symptom reduction . Path analysis revealed two paths to a decrease in self-reported unexplained physical symptoms : from more negative affectivity via more psychological attribution and more pretreatment anxiety , and from more somatic attribution via more psychological attribution and more pretreatment anxiety . CONCLUSION Intervention and control groups did not differ in symptom reduction . Reduction of self-reported medically unexplained symptoms was well predicted by patient-related symptom perception variables , whereas the prediction of change in registered symptoms and consultations requires a different model BACKGROUND Patients diagnosed as having somatization disorder ( SD ) who present with a lifetime history of multiple , medically unexplained physical symptoms represent a significant challenge to health care providers . To date , no psychotherapeutic or pharmacologic intervention has been found to produce clinical ly meaningful improvement in symptoms or functioning of patients with SD . We examined the efficacy of cognitive-behavioral therapy ( CBT ) for SD . METHODS Eighty-four participants meeting criteria for SD were r and omly assigned to 1 of 2 conditions : ( 1 ) st and ard medical care augmented by a psychiatric consultation intervention or ( 2 ) a 10-session , manualized , individually administered CBT regimen added to the psychiatric consultation intervention . Assessment s were conducted at baseline and 3 , 9 , and 15 months after baseline . The primary outcome measure was the severity scale of the Clinical Global Impression Scale for Somatization Disorder ( CGI-SD ) . Secondary outcome measures were responder status as determined by clinical ratings , self-reported measures of physical functioning and somatic symptoms , and health care utilization assessed via medical records . RESULTS Fifteen months after baseline , somatization symptoms were significantly less severe in the group treated with CBT ( 0.84 points on the CGI-SD 7-point scale ) ( P<.001 ) . Patients treated with CBT also were significantly more likely to be rated as either very much improved or much improved than patients treated with only augmented st and ard medical care ( 40 % [ n = 17 ] vs 5 % [ n = 2 ] ) . Cognitive-behavioral therapy was associated with greater improvements in self-reported functioning and somatic symptoms and a greater decrease in health care costs . CONCLUSION For patients diagnosed as having SD , CBT may produce clinical benefits beyond those that result from the current state-of-the-art treatment This pilot study was conducted to determine the effect of an innovative reflecting interview on the health care utilization , physical health , mental function , and health care satisfaction of high-utilizing primary care patients with medically unexplained physical symptoms . Twenty-four high-utilizing patients met study selection criteria and were r and omly assigned to a no-intervention control group or a reflecting interview intervention group . Outcomes were measured at 4 weeks , 6 months , and 1 year after the date of study enrollment . Results indicated that high-utilizing patients with medically unexplained physical symptoms who participated in a reflecting interview had reduced total health care costs , primarily through the reduction of hospitalization or inpatient expenses , despite a modest increase in outpatient primary care clinic visits . These data suggest that participation in a reflecting interview and regular visits with a primary care clinician can decrease health care utilization without adversely affecting patient satisfaction Background A pilot trial in Sri Lanka among patients with medically unexplained symptoms revealed that cognitive – behavioural therapy ( CBT ) administered by a psychiatrist was efficacious . Aims To evaluate CBT provided by primary care physicians in a comparison with structured care . Method A r and omised control trial ( n=75 in each arm ) offered six 30 min sessions of structured care or therapy . The outcomes of the two interventions were compared at 3 months , 6 months , 9 months and 12 months . Results In each arm , 64 patients ( 85 % ) completed the three m and atory sessions . No difference was observed between groups in mean scores on the General Health Question naire or the Bradford Somatic Inventory , or in number of complaints or patient-initiated consultations at 3 months . For both groups , all outcome measures improved at 3 months , and remained constant in the follow-up assessment s. Conclusions Cognitive – behavioural therapy given by primary care physicians after a short course of training is no more efficacious than structured care . Natural remission is an unlikely explanation for improvements in people with chronic medically unexplained symptoms , but lack of a ‘ treatment as usual ’ arm limits further conclusions . Further research on enhanced structured care , medical assessment and structured care incorporating simple elements of CBT principles is worthy of consideration We sought to determine whether an intervention labeled “ biofeedback ” could be implemented with patients who were diagnosed with “ functional ” disorders ( Irritable Bowel Syndrome , Fibromyagia/Chronic Fatigue Syndrome , Myofascial Pain , Anxiety with somatic features , or Noncardiac Chest Pain ) , in a primary care setting , and whether cost savings through lowered utilization of medical services would be realized . Seventy patients were initially r and omized into a treatment group or comparison group based on willingness to participate . Ultimately , 19 patients completed treatment and 30 were followed through usual treatment as a comparison . Treatment patients completed symptom diaries while working with a biofeedback therapist in the primary care facility . Both group 's medical expenses were tracked for 6 months prior to and 6 months after the treatment time interval . Patients in the treatment group lowered symptom frequency and severity significantly . Medical costs were differentially reduced in this group such that all costs were $ 72 less in the treatment group and $ 9 in the comparison for the 6 months following the treatment time period . ( p < .001 ) . Unfortunately , a large group of assigned treatment patients did not start or complete treatment . These patients had high initial costs and went up even higher post . No comparable group could be found among the controls , limiting any inference regarding cost/benefit . Biofeedback based interventions for “ functional ” disorders can be easily integrated into primary care setting s , can reduce symptoms , and may be able to reduce overall medical costs in this group of patients known as heavy utilizers BACKGROUND Research on the management and the outcome of treatment of medically unexplained symptoms is very limited . Development of simple but effective techniques for treatment and demonstration of their effectiveness when applied in primary health care are needed . METHODS A r and omized controlled trial was carried out with follow-up assessment s at 3 months after baseline assessment s using the Short Explanatory Model Interview ( SEMI ) , General Health Question naire ( GHQ-30 ) , Bradford Somatic Inventory ( BSI ) and patient satisfaction on a visual analogue scale . The study was carried out in a general out-patient clinic in Sri Lanka . The intervention group received six , 30 min sessions based on the principles of cognitive behavioural therapy over a period of 3 months . The control group received st and ard clinical care . RESULTS Eighty patients out of the 110 patients referred , were eligible . Sixty-eight were r and omly allocated equally to the control and treatment groups . All 34 in the treatment group accepted the treatment offer and 22 completed between three and six sessions . At 3 months , 24 in the treatment and 21 in the control group completed follow-up assessment s. Intention-to-treat analysis revealed significant differences in mean scores of outcome measures ( adjusted for baseline scores ) between control and intervention groups respectively -- complaints 6.1 and 3.8 ( P = 0.001 ) , GHQ 10.4 and 6.3 ( P = 0.04 ) , BSI score 15.6 and 132 ( P < 0 - 01 ) , visits 7.9 and 3.1 ( P = 0.004 ) . CONCLUSIONS Intervention based on cognitive behavioural therapy is feasible and acceptable to patients with medically unexplained symptoms from a general out- patients clinic in Sri Lanka . It had a significant effective in reducing symptoms , visits and distress , and in increasing patient satisfaction OBJECTIVE To evaluate the diagnosis of patients with somatisation disorders in primary care , and the effectiveness of coordinated care and evidence -based care planning on psychiatric symptoms and quality of life for these patients . DESIGN , SETTING AND PARTICIPANTS This was a project of the SA HealthPlus Coordinated Care Trial , comprising a r and omised controlled trial of 124 subjects recruited by general practitioners in southern Adelaide . Eligible patients had a GP diagnosis of somatisation , including unexplained physical symptoms as part of anxiety , chronic pain or somatoform disorders . Diagnoses were checked using the Composite International Diagnostic Interview ( CIDI ) . The study was conducted from December 1997 to December 1999 . INTERVENTION A care plan including treatment for depression and anxiety disorders , a containment strategy for somatisation , and service coordinator-assisted self-management . Control patients received st and ard treatment . MAIN OUTCOME MEASURES Psychiatric symptoms ; quality of life ; medication use ; and depression , anxiety and hostility scores . RESULTS Compared with CIDI diagnoses , mood disorders in patients were underdiagnosed by GPs ( 64 v 31 ) , particularly major depression ( 46 v 1 ) . At 12 months , the intervention group showed reductions in depression ( P = 0.002 ) , guilt ( P = 0.006 ) and anxiety ( state , P = 0.043 ; trait , P = 0.001 ) . Compared with the control group , physical role functioning improved for the intervention group ( P = 0.006 ) , and their medication use decreased by 8.9 % . CONCLUSIONS Conservative management , treatment of depression , and case management by service coordinators is effective in managing somatising patients in primary care . GPs require training in the diagnosis of depression and how to say " no " to patients with unexplained physical symptoms who request further unnecessary investigations or referrals OBJECTIVE To conduct a feasibility and efficacy trial of mindfulness therapy in somatization disorder and functional somatic syndromes such as fibromyalgia , irritable bowel syndrome , and chronic fatigue syndrome , defined as bodily distress syndrome ( BDS ) . METHODS We r and omized 119 patients to either mindfulness therapy ( mindfulness-based stress reduction and some cognitive behavioral therapy elements for BDS ) or to enhanced treatment as usual ( 2-hour specialist medical care and brief cognitive behavioral therapy for BDS ) . The primary outcome measure was change in physical health ( SF-36 Physical Component Summary ) from baseline to 15-month follow-up . RESULTS The study is negative as we could not demonstrate a different development over time for the two groups ( F(3,2674)=1.51 , P=.21 ) . However , in the mindfulness therapy group , improvement was obtained toward the end of treatment and it remained present at the 15-month follow-up , whereas the enhanced treatment as usual group achieved no significant change until 15-month follow-up . The change scores averaged half a st and ard deviation which amounts to a clinical ly significant change , 29 % changed more than 1 st and ard deviation . Significant between-group differences were observed at treatment cessation . CONCLUSION Mindfulness therapy is a feasible and acceptable treatment . The study showed that mindfulness therapy was comparable to enhanced treatment as usual in improving quality of life and symptoms . Nevertheless , considering the more rapid improvement following mindfulness , mindfulness therapy may be a potentially useful intervention in BDS patients . Clinical ly important changes that seem to be comparable to a CBT treatment approach were obtained . Further research is needed to replicate or even exp and these findings Background : Patients with medically unexplained symptoms ( MUS ) are frequent in primary care and substantially impaired in their quality of life ( QoL ) . Specific training of general practitioners ( GPs ) alone did not demonstrate sustained improvement at later follow-up in current review s. We evaluated a collaborative group intervention . Methods : We conducted a cluster r and omized controlled trial . Thirty-five GPs recruited 304 MUS patients ( intervention group : 170 ; control group : 134 ) . All GPs were trained in diagnosis and management of MUS ( control condition ) . Eighteen r and omly selected intervention GPs participated in training for a specific collaborative group intervention . They conducted 10 weekly group sessions and 2 booster meetings in their practice s , together with a psychosomatic specialist . Six and 12 months after baseline , QoL was assessed with the Short-Form 36 . The primary outcome was the physical composite score ( PCS ) , and the secondary outcome was the mental composite score ( MCS ) . Results : At 12 months , intention-to-treat analyses showed a significant between-group effect for the MCS ( p = 0.023 ) but not for the PCS ( p = 0.674 ) . This effect was preceded by a significant reduction of somatic symptom severity ( 15-item somatic symptom severity scale of the Patient Health Question naire , PHQ-15 ) at 6 months ( p = 0.008 ) that lacked significance at 12 months ( p = 0.078 ) . As additional between-group effects at 12 months , per- protocol analyses showed less health anxiety ( Whiteley-7 ; p = 0.038 ) and less psychosocial distress ( PHQ ; p = 0.024 ) ; GP visits were significantly ( p = 0.042 ) reduced in the intervention group . Conclusions : Compared to pure GP training , collaborative group intervention achieved a progressive , clinical ly meaningful improvement in mental but not physical QoL. It could bridge gaps between general practice and mental health care Objectives : Functional ( psychogenic or somatoform ) symptoms are common in neurology clinics . Cognitive-behavioral therapy ( CBT ) can be an effective treatment , but there are major obstacles to its provision in practice . We tested the hypothesis that adding CBT-based guided self-help ( GSH ) to the usual care ( UC ) received by patients improves outcomes . Methods : We conducted a r and omized trial in 2 neurology services in the United Kingdom . Out patients with functional symptoms ( rated by the neurologist as “ not at all ” or only “ somewhat ” explained by organic disease ) were r and omly allocated to UC or UC plus GSH . GSH comprised a self-help manual and 4 half-hour guidance sessions . The primary outcome was self-rated health on a 5-point clinical global improvement scale ( CGI ) at 3 months . Secondary outcomes were measured at 3 and 6 months . Results : In this trial , 127 participants were enrolled , and primary outcome data were collected for 125 . Participants allocated to GSH reported greater improvement on the primary outcome ( adjusted common odds ratio on the CGI 2.36 [ 95 % confidence interval 1.17–4.74 ; p = 0.016 ] ) . The absolute difference in proportion “ better ” or “ much better ” was 13 % ( number needed to treat was 8) . At 6 months the treatment effect was no longer statistically significant on the CGI but was apparent in symptom improvement and in physical functioning . Conclusions : CBT-based GSH is feasible to implement and efficacious . Further evaluation is indicated . Classification of evidence : This study provides Class III evidence that CBT-based GSH therapy improves self-reported general health , as measured by the CGI , in patients with functional neurologic symptoms OBJECTIVE Our aim was to evaluate the effect of an educational program design ed to improve care for somatizing patients in primary care . METHOD Evaluation was performed during routine clinical care in a cluster r and omized controlled trial . Patients were included consecutively , and those with a high score on rating scales for somatization were selected for follow-up ( n=911 ) . Follow-up was conducted 3 months ( response rate=0.74 ) and 12 months ( response rate=0.69 ) after inclusion using question naires measuring quality of life ( Medical Outcomes Study 36-Item Short Form ) , disability days ( WHO 's Disability Assessment Schedule ) , somatization ( Whiteley-7 and Symptom Checklist Somatic Symptom Scale ) and patient satisfaction ( European Project on Patient Evaluation of General Practice Care ) . We analyzed differences from baseline to follow-up and compared these for intervention and control groups . RESULTS Self-reported health improved in both intervention and control groups during follow-up for patients with a high score for somatization , but changes were small . We could not demonstrate any difference between the control group and the intervention group with regard to our primary outcome ' physical functioning . ' Patients in the intervention group tended to be more satisfied at 12-month follow-up than those in the control group , but this difference fell short of statistical significance . CONCLUSION Training of primary care physicians showed no statistically significant effect on clinical outcome and showed nonsignificant improvement in patient satisfaction with care for patients with a high score for somatization BACKGROUND AND AIM The aim of the controlled therapy study was to evaluate the effect of a 6 session biofeedback intervention program on cognitive aspects of patients with somatoform disorders . The treatment consisted of psycho-physiological demonstrations how mental processes can influence biological functions . We expected this treatment to be of high credibility , to change maladaptive cognitions , to enhance acceptance of psychosocial causal attribution and to improve coping . METHODS Patients were assessed using a structured interview to diagnose somatization syndrome ( SSI-8 ) and comorbidity according to DSM-IV criteria . Fifty patients were recruited and r and omly assigned to biofeedback treatment or control relaxation group . Participants completed a question naire battery assessing cognitive characteristics , causal attributions and controllability before and after intervention as well as evaluation protocol s for each session . RESULTS The results suggest that biofeedback modified the patients ' cognitive schemata : Patients with somatization syndrome of the biofeedback group showed a greater reduction of catastrophizing of somatic sensations and higher acceptance of psychosocial causal attributions than the control group . Both groups improved significantly in the conviction of self-efficacy BACKGROUND Patients presenting with medically unexplained physical symptoms ( MUPS ) typically present with significant distress and marked impairment in functioning and pose a unique challenge to health care providers . The purpose of this study was to examine the efficacy of a psychophysiological treatment ( PT ) for MUPS . METHODS Thirty-eight participants meeting criteria for subthreshold somatization disorder ( abridged somatization ) were r and omly assigned to one of two conditions : ( 1 ) st and ard medical care augmented by a psychiatric consultation intervention ( wait-list ) or ( 2 ) a 10-session , manualized , individually-administered PT added to the psychiatric consultation intervention . Assessment s were conducted at baseline , at midpoint ( after four sessions ) , and after completing the last session . The primary outcome measure was the severity scale of the Clinical Global Impression Scale anchored for Somatic Symptoms ( CGI-SD ) . Secondary outcome measures were responder status as determined by clinical ratings , self-report measures of mental and physical functioning . RESULTS At the end of the trial , the severity ( and frequency ) of physical symptoms improved significantly more ( p<0.05 ) in the intervention group . The average improvement in the CGI-SD was 0.80 points greater in the intervention group than in the wait-list group . PT was also associated with greater improvements in self-reported functioning and depressive symptomatology . The effect sizes at the final assessment point indicate that this intervention had a robust effect on complex somatic symptom presentations . CONCLUSION For patients with high levels of MUPS ( abridged somatization ) , PT produces significant improvements in symptoms and functional status Objective To evaluate the effectiveness and feasibility of a cognitive-behavioral program for patients in primary care units who were diagnosed as having abridged somatization disorder . Method A multicenter , r and omized controlled trial was design ed . One hundred sixty-eight patients were recruited from 29 primary care units and r and omly assigned to one of three arms : treatment as usual ( TAU ) , individual cognitive-behavioral therapy ( CBT ) , and group CBT . Somatic symptoms were measured using the Screening for Somatoform Disorders and the Severity of Somatic Symptoms scale . The Hamilton Anxiety Rating Scale and the Hamilton Depression Rating Scale were used to assess the severity of anxiety and depression . Results Individual CBT achieves greater changes in the Screening for Somatoform Disorders posttreatment compared with group CBT ( mean [ 95 % confidence interval ] , 14.17 [ 11.9–16.3 ] versus 11.63 [ 9.4–13.7 ] , p < .001 ) . These improvements were observed at 6 and 12 months ( p < .001 and p < .001 , respectively ) . For individual CBT versus TAU , the number-needed-to-treat was 8 , whereas for group CBT versus TAU , the number-needed-to-treat was 9 . Individual CBT treatment result ed in lower anxiety scores compared with group CBT and TAU ( 7.33 [ 5.4–9.2 ] versus 11.47 [ 9.4–13.9 ] versus 13.07 [ 10.9–15.2 ] , p < .001 ) posttreatment . Individual CBT and group CBT were associated with sustained benefits at 12-month follow-up compared with TAU ( 8.6 [ 6.6–10.6 ] versus 9.28 [ 7.2–11.2 ] versus 16.2 [ 13.9–18.5 ] , p < .001 ) . Depressive symptoms were lower for individual CBT posttreatment than for TAU ( 6.96 [ 5.3–8.6 ] versus 10.87–12.7 ] , p < .01 ) . Conclusions CBT in individual and group setting s results in significant improvements in somatic symptoms among patients with somatoform abridged disorder compared with TAU . Individual CBT results in greater posttreatment improvements at 6-month and 12-month follow-ups . Trial Registration : current controlled trials identifier IS RCT N69944771 BACKGROUND Somatizing patients are a challenge to general practitioners ( GPs ) . A cluster r and omized controlled trial was conducted to asses the effect of specific communication techniques delivered by GPs on somatizing patients ' self-perceived health . METHOD Thirty-nine GPs were assigned r and omly to two parallel groups . GPs in the intervention group treated somatic patients according to specific communication techniques focused on offering a physical explanation - release of hormones - and approaching sensitive topics in the patient 's experience indirectly . Control GPs used the st and ard Goldberg reattribution technique . A total of 156 patients , aged 18 - 65 years , were selected r and omly from a list of 468 patients with six or more active symptoms for women and four or more for men . All patients had six programmed 30-min consultations . Health-related quality of life ( assessed with the 36-item Short-Form Health Survey , SF-36 ) and a summary utility index were used as outcome measures . Patients were interviewed at home at baseline and at 3 , 8 and 12 months after the beginning of the intervention . RESULTS Patients in both groups improved in all dimensions of the SF-36 . The time course of the quality of life was significantly better for the intervention group in five of the eight scales of the SF-36 ( bodily pain , mental health , physical functioning , vitality , and social functioning ) and in the utility index ( p<0.039 ) . CONCLUSIONS Communication techniques were found to have a clinical ly relevant impact on body pain . This finding , together with a trend towards better scores in the remaining scales , justifies the use of these techniques in psychosocial interventions delivered to patients with medically unexplained symptoms The objective of this study was to evaluate the effect of a short cognitive behavioural group therapy programme for somatization disorder in primary care . The treatment model was focused on patient education and stress relaxation . A controlled and prospect i ve study design was used with repeated assessment s of the patients ’ perception of their psychosocial problems , psychological distress and medication usage . The results were analysed up to 6 months after treatment and showed the treated patients to be moderately but significantly improved with respect to physical illness and somatic preoccupation , hypochondriasis , and medication usage . In a control group of untreated patients no such improvements were observed . In summary , the short group treatment programme used in this study may be beneficial for patients with somatization disorders . With some modifications it might be useful to practitioners in primary care for the management of psychosomatic disorders To identify an effective method of treating patients with somatization disorder ( SD ) , the authors conducted a r and omized controlled clinical trial of group therapy with 70 SD patients . Primary care physicians treating all patients in the study received a consultation letter offering treatment recommendations for SD . The experimental patients were invited to attend eight group therapy sessions in addition to the consultation provided to their physicians ; 45 % attended one or more sessions . The experimental patients reported significantly better physical ( P < 0.05 ) and mental ( P < 0.01 ) health in a 1-year period during and after group therapy . The more group sessions SD patients attended , the greater the improvement in general and mental health . The 52 % net savings in health care charges associated with group therapy plus the consultation indicate that it is economically feasible to improve outcomes without escalating the cost of care in this group of high users of medical re sources Background : Patients with persistent medically unexplained symptoms often exhibit general dysfunction and psychiatric comorbidity and frequently resist psychiatric referral . The aim of this study was to evaluate the efficacy of a collaborative care model including training for general practitioners ( GPs ) and a psychiatric consultation model for patients with persistent medically unexplained symptoms in general practice . Method : R and omised controlled trial . Cluster r and omisation at GP practice s and multilevel analysis were performed . A total of 81 patients from 36 general practice s completed the study . A collaborative care model of training and psychiatric consultation in general practice in the presence of the GP was compared with training plus care as usual by the GP . Outcome assessment on the patients ’ well-being , functioning and utilisation of health care services was performed 6 weeks and 6 months later . Results : All the patients had somatoform disorders ( Whitely Index 7.46 ) , and 86 % had comorbid psychiatric disorders . In the intervention group , the severity of the main medically unexplained symptoms decreased by 58 % . The patients ’ social functioning improved . The utilization of health care was lower than in the care as usual group . Conclusions : A collaborative care model combining training with psychiatric consultation in the general practice setting is an effective intervention in the treatment of persistent medically unexplained symptoms . Anxiety and depressive disorders are highly comorbid in this group . The findings warrant a larger study |
728 | 24,021,427 | Studies have indicated that EMFs produced at cell-phone frequencies cause no-effect on the heart .
At greater EMF strengths or shorter exposures , the ability of the body to develop compensation mechanisms is reduced and the potential for heart-related effects increases .
It is noteworthy that diseases of heart tissues such as myocardial ischemia can also be successfully treated using EMF . | The use of electrical devices has gradually increased throughout the last century , and scientists have suggested that electromagnetic fields ( EMF ) generated by such devices may have harmful effects on living creatures .
This work represents a systematic review of collective scholarly literature examining the effects of EMFs on the heart .
Although most works describing effects of EMF exposure have been carried out using city electric frequencies ( 50–60 Hz ) , a consensus has not been reached about whether long- or short-term exposure to 50–60 Hz EMF negatively affects the heart . | Abstract Braune , S. , Riedel , A. , Schulte-Mönting , J. and Raczek , J. Influence of a Radiofrequency Electromagnetic Field on Cardiovascular and Hormonal Parameters of the Autonomic Nervous System in Healthy Individuals . Radiat . Res . 158 , 352–356 ( 2002 ) . The potential health risks of radiofrequency electromagnetic fields ( EMFs ) emitted by mobile phones are of considerable public interest . The present study investigated the hypothesis , based on the results of our previous study , that exposure to EMFs can increase sympathetic vasoconstrictor activity . Forty healthy young males and females underwent a single-blind , placebo-controlled protocol once on each of two different days . Each investigation included successive periods of placebo and EMF exposure , given in a r and omized order . The exposure was implemented by a GSM-like signal ( 900 MHz , pulsed with 217 Hz , 2 W ) using a mobile phone mounted on the right-h and side of the head in a typical telephoning position . Each period of placebo exposure and of EMF exposure consisted of 20 min of supine rest , 10 min of 70 ° upright tilt on a tilt table , and another 20 min of supine rest . Blood pressure , heart rate and cutaneous capillary perfusion were measured continuously . In addition , serum levels of norepinephrine , epinephrine , cortisol and endothelin were analyzed in venous blood sample s taken every 10 min . Similar to the previous study , systolic and diastolic blood pressure each showed slow , continuous , statistically significant increases of about 5 mmHg during the course of the protocol . All other parameters either decreased in parallel or remained constant . However , analysis of variance showed that the changes in blood pressure and in all other parameters were independent of the EMF exposure . These findings do not support the assumption of a nonthermal influence of EMFs emitted by mobile phones on the cardiovascular autonomic nervous system in healthy humans The present study used exercise testing to examine the effects of 60-Hz electric and magnetic field exposure . Eleven males , 21 - 29 years , were tested during four experimental sessions ( counterbalanced order and double-blind design ) . These included either 45-min exercise ( 50 % of VO2 max ) or no-exercise periods followed by either real field ( 9-kV/m , 16-A/m ) or sham exposure for 2 h in a 60-Hz human exposure facility . Exercise produced a decrease in plasma volume and increases ( p less than 0.05 ) in lactic acid , cortisol , growth hormone and testosterone levels , but these were not different under real and sham field conditions during the 2-h recovery periods . During no-exercise sessions , cardiac interbeat interval was increased ( p less than 0.05 ) , i.e. , heart rate was slower , when subjects were exposed to real fields . Our results suggest that future studies should focus on evaluation of the effects of 60-Hz fields on the entire process of exercise-induced activation and recovery This human exposure study examined the relationship between field strength and biological response and tested whether the exposure levels at which the greatest effects occur differ for different endpoints . Three matched groups of 18 men each participated in two 6 h exposure test sessions . All subjects were sham exposed in one session . In the other session , each group of subjects was exposed at a different level of combined electric and magnetic field strength ( low group:6 kV/m , 10 microT ; medium group:9 kV/m , 20 microT ; and high group : 12 kV/m , 30 microT ) . The study was performed double blind , with exposure order counterbalanced . Significant slowing of heart rate , as well as alternations in the latency and amplitude of event-related brain potential measures derived from the electro encephalogram ( EEG ) , occurred in the group exposed to the 9 kV/m , 20 microT combined field ( medium group ) . Exposure at the other field strength levels had no influence on cardiac measures and differential effects on EEG activity . Significant decrements in reaction time and in performance accuracy on a time estimation task were observed only in the low group . These results provide support for the hypothesis that humans may be more responsive to some combinations or levels of field strength than to others and that such differences in responsivity may depend , in part , on the endpoint of interest This study investigated the problem of the influence of 50 Hz magnetic field ( MF ) on human heart rate variability ( HRV ) . The exposure system was a commercial device for magnetotherapy , generating field of the strength of 500 microT at the center of the coil , 150 - 200 microT at the position of human subjects ' heart and 20 - 30 microT at the position of subjects ' head . The exposure protocol s , applied r and omly , were either " half hour MF-off/half hour MF-on " or " half hour MF-off/half hour MF-off . " The phonocardiographic ( PhCG ) signal of 15 volunteers were obtained during exposure and used for calculation of time-domain HRV parameters ( mean time between heart beats ( N-N ) , st and ard deviation of time between heart beats ( SDNN ) , and the number of differences of successive beat-to-beat intervals greater than 50 ms , divided by the total number of beat-to-beat intervals ( pNN50 ) ) and nonlinear HRV measures ( approximate entropy ( ApEn ) , detrended fluctuation scaling exponents ) . The protocol MF-off/MF-on was applied in nine subjects . Repeated measures ANOVA ( RMANOVA ) performed for Mf-off/MF-off protocol indicated no statistical difference among four 15 min intervals of HRV data ( P value > 20 % for all parameters except for N-N , where P = 3.7 % ) . RMANOVA followed by the post hoc Tukey test performed for Mf-off/MF-on protocol indicated a statistically significant difference during MF on for N-N ( 8 % increase , P < .1 % ) , SDNN ( 40 % increase , P = 1.1 % ) , and pNN50 ( 110 % increase , P < .1 % ) . The results of the analysis indicate that the changes of these parameters could be associated with the influence of MF Recent studies indicate that exposure to extremely low frequency magnetic fields ( ELF MFs ) influences human electroencephalographic ( EEG ) alpha activity and pain perception . In the present study we analyse the effect on electrical EEG activity in the alpha b and ( 8 - 13 Hz ) and on nociception in 40 healthy male volunteers after 90-min exposure of the head to 50 Hz ELF MFs at a flux density of 40 or 80 microT in a double-blind r and omized sham-controlled study . Since cardiovascular regulation is functionally related to pain modulation , we also measured blood pressure ( BP ) and heart rate ( HR ) during treatment . Alpha activity after 80 microT magnetic treatment almost doubled compared to sham treatment . Pain threshold after 40 microT magnetic treatment was significantly lower than after sham treatment . No effects were found for BP and HR . We suggest that these results may be explained by a modulation of sensory gating processes through the opioidergic system , that in turn is influenced by magnetic exposure This study investigates the effect of exposure to a mobile phone-like radiofrequency ( RF ) electromagnetic field on people with atopic dermatitis ( AD ) . Fifteen subjects with AD were recruited and matched with 15 controls without AD . The subjects were exposed for 30 min to an RF field at 1 W/kg via an indoor base station antenna attached to a 900 MHz GSM mobile phone . Blood sample s for ELISA analysis of the concentration of substance P ( SP ) , tumor necrosis factor receptor 1 ( TNF R1 ) , and brain derived neurotrophic factor ( BDNF ) in serum were drawn before and after the provocation ( exposure/sham ) . Baseline heart rate and heart rate variability , local blood flow , and electrodermal activity were also recorded . No significant differences between the subject groups were found for baseline neurophysiological data . The cases displayed a serum concentration of TNF R1 significantly higher than the control subjects and a significantly lower serum concentration of BDNF in the baseline condition . For SP there was no difference between groups . However , no effects related to RF exposure condition were encountered for any of the measured substances . As to symptoms , a possible correlation with exposure could not be evaluated , due to too few symptom reports . The result of the study does not support the hypothesis of an effect of mobile phone-like RF exposure on serum levels of SP , TNF R1 , and BDNF in persons with AD University students use mobile phones frequently . We previously showed that there was no association between mobile phone use and EMF health hazards among university students . As our previous study was based only on self-reported symptoms this double-blind study was design ed to answer two basic questions . Firstly , are self-reported hypersensitive individuals capable of sensing whether there is a real/sham microwave exposure ? Secondly , do hypersensitive patients show alterations in their biological parameters such as heart rate , respiration , and blood pressure during microwave exposure ? The study consisted of a preliminary screening phase and two subsequent complementary phases . In the 1st phase , 700 students were screened for EMF hypersensitivity . Fifty two participants were hypersensitive individuals but after applying the exclusion criteria only 28 students were invited to take part in the 2nd and 3rd phase of the study , but only 20 students ( 71.4 % ) declared their informed consent . In the 2nd phase , these self reported hypersensitive participants , were exposed/sham exposed to microwave radiation emitted from a mobile phone for 10 minutes and they were asked if they could sense the existence of microwave radiation . In the 3rd phase , all students were connected to ICU monitoring devices and their basic physiological parameters were recorded precisely . Among self-reported symptoms reported in our previous study , in this study only problem in concentration ( P < 0.05 ) and low back pain ( P < 0.05 ) were associated with mobile phone use . Furthermore , there was a significant association between the location of mobile phone during talk and the overall score of the severity of the symptoms ( P < 0.001 ) . When the participants were asked to report their perception about the real and sham exposures , only 5 students ( 25 % ) could discriminate the real exposure/sham exposure phases . This relative frequency can be only due to chance . In the 3rd phase all of the 20 participants were connected to intensive care unit monitors and the changes in their heart rate , respiration , and blood pressure during real/sham exposure were recorded . No statistically significant changes between the means of these parameters in real/sham exposure were observed . Our findings clearly confirm the results obtained inother provocative studies . These data also indicate the possible role of psychological factors in electromagnetic hypersensitivity The aim of the present study was to investigate the effect of exposure to a mobile phone-like radiofrequency ( RF ) electromagnetic field on persons experiencing subjective symptoms when using mobile phones ( MP ) . Twenty subjects with MP-related symptoms were recruited and matched with 20 controls without MP-related symptoms . Each subject participated in two experimental sessions , one with true exposure and one with sham exposure , in r and om order . In the true exposure condition , the test subjects were exposed for 30 min to an RF field generating a maximum SAR(1 g ) in the head of 1 W/kg through an indoor base station antenna attached to a 900 MHz GSM MP . The following physiological and cognitive parameters were measured during the experiment : heart rate and heart rate variability ( HRV ) , respiration , local blood flow , electrodermal activity , critical flicker fusion threshold ( CFFT ) , short-term memory , and reaction time . No significant differences related to RF exposure conditions were detected . Also no differences in baseline data were found between subject groups , except for the reaction time , which was significantly longer among the cases than among the controls the first time the test was performed . This difference disappeared when the test was repeated . However , the cases differed significantly from the controls with respect to HRV as measured in the frequency domain . The cases displayed a shift in low/high frequency ratio towards a sympathetic dominance in the autonomous nervous system during the CFFT and memory tests , regardless of exposure condition . This might be interpreted as a sign of differences in the autonomous nervous system regulation between persons with MP related subjective symptoms and persons with no such symptoms Terrestrial Trunked Radio ( TETRA ) technology ( " Airwave " ) has led to public concern because of its potential interference with electrical activity in the brain . The present study is the first to examine whether acute exposure to a TETRA base station signal has an impact on cognitive functioning and physiological responses . Participants were exposed to a 420 MHz TETRA signal at a power flux density of 10 mW/m(2 ) as well as sham ( no signal ) under double-blind conditions . Fifty-one people who reported a perceived sensitivity to electromagnetic fields as well as 132 controls participated in a double-blind provocation study . Forty-eight sensitive and 132 control participants completed all three sessions . Measures of short-term memory , working memory , and attention were administered while physiological responses ( blood volume pulse , heart rate , skin conductance ) were monitored . After applying exclusion criteria based on task performance for each aforementioned cognitive measure , data were analyzed for 36 , 43 , and 48 sensitive participants for these respective tasks and , likewise , 107,125 , and 129 controls . We observed no differences in cognitive performance between sham and TETRA exposure in either group ; physiological response also did not differ between the exposure conditions . These findings are similar to previous double-blind studies with other mobile phone signals ( 900 - 2100 MHz ) , which could not establish any clear evidence that mobile phone signals affect health or cognitive function |
729 | 28,885,719 | Our data suggest that , in NDMM patients treated with upfront ASCT , post-transplant consolidation may improve depth of response , but does not add to OS or PFS , compared to lenalidomide maintenance alone . | BACKGROUND In newly diagnosed multiple myeloma ( NDMM ) , autologous stem cell transplantation ( ASCT ) remains the st and ard approach for transplant-eligible patients .
To control the inevitable relapse , post-transplant consolidation/maintenance strategies are commonly used .
However , the benefit of post-transplant consolidation is still uncertain METHOD : We conducted a systematic review of phase II/III studies to compare the efficacy of post-ASCT consolidation plus lenalidomide maintenance ( CON+LEN ) vs lenalidomide maintenance alone ( LEN alone ) in NDMM . | BACKGROUND High-dose melphalan plus autologous stem-cell transplantation ( ASCT ) is the st and ard approach in transplant-eligible patients with newly diagnosed myeloma . Our aims were to compare consolidation with high-dose melphalan plus ASCT versus chemotherapy ( cyclophosphamide and dexamethasone ) plus lenalidomide , and maintenance with lenalidomide plus prednisone versus lenalidomide alone . METHODS We did an open-label , r and omised , multicentre , phase 3 study at 59 centres in Australia , Czech Republic , and Italy . We enrolled transplant-eligible patients with newly diagnosed myeloma aged 65 years or younger . Patients received a common induction with four 28-day cycles of lenalidomide ( 25 mg , days 1 - 21 ) and dexamethasone ( 40 mg , days 1 , 8 , 15 , and 22 ) and subsequent chemotherapy with cyclophosphamide ( 3 g/m(2 ) ) followed by granulocyte colony-stimulating factor for stem-cell mobilisation and collection . Using a 2 × 2 partial factorial design , we r and omised patients to consolidation with either chemotherapy plus lenalidomide ( six cycles of cyclophosphamide [ 300 mg/m(2 ) , days 1 , 8 , and 15 ] , dexamethasone [ 40 mg , days 1 , 8 , 15 , and 22 ] , and lenalidomide [ 25 mg , days 1 - 21 ] ) or two courses of high-dose melphalan ( 200 mg/m(2 ) ) and ASCT . We also r and omised patients to maintenance with lenalidomide ( 10 mg , days 1 - 21 ) plus prednisone ( 50 mg , every other day ) or lenalidomide alone . A simple r and omisation sequence was used to assign patients at enrolment into one of the four groups ( 1:1:1:1 ratio ) , but the treatment allocation was disclosed only when the patient reached the end of the induction and confirmed their eligibility for consolidation . Both the patient and the treating clinician did not know the consolidation and maintenance arm until that time . The primary endpoint was progression-free survival assessed by intention-to-treat . The trial is ongoing and some patients are still receiving maintenance . This study is registered at Clinical Trials.gov , number NCT01091831 . FINDINGS 389 patients were enrolled between July 6 , 2009 , and May 6 , 2011 , with 256 eligible for consolidation ( 127 high-dose melphalan and ASCT and 129 chemotherapy plus lenalidomide ) and 223 eligible for maintenance ( 117 lenalidomide plus prednisone and 106 lenalidomide alone ) . Median follow-up was 52·0 months ( IQR 30·4 - 57·6 ) . Progression-free survival during consolidation was significantly shorter with chemotherapy plus lenalidomide compared with high-dose melphalan and ASCT ( median 28·6 months [ 95 % CI 20·6 - 36·7 ] vs 43·3 months [ 33·2 - 52·2 ] ; hazard ratio [ HR ] for the first 24 months 2·51 , 95 % CI 1·60 - 3·94 ; p<0·0001 ) . Progression-free survival did not differ between maintenance treatments ( median 37·5 months [ 95 % CI 27·8-not evaluable ] with lenalidomide plus prednisone vs 28·5 months [ 22·5 - 46·5 ] with lenalidomide alone ; HR 0·84 , 95 % CI 0·59 - 1·20 ; p=0·34 ) . Fewer grade 3 or 4 adverse events were recorded with chemotherapy plus lenalidomide than with high-dose melphalan and ASCT ; the most frequent were haematological ( 34 [ 26 % ] of 129 patients vs 107 [ 84 % ] of 127 patients ) , gastrointestinal ( six [ 5 % ] vs 25 [ 20 % ] ) , and infection ( seven [ 5 % ] vs 24 [ 19 % ] ) . Haematological serious adverse events were reported in two ( 2 % ) patients assigned chemotherapy plus lenalidomide and no patients allocated high-dose melphalan and ASCT . Non-haematological serious adverse events were reported in 13 ( 10 % ) patients assigned chemotherapy plus lenalidomide and nine ( 7 % ) allocated high-dose melphalan and ASCT . During maintenance , adverse events did not differ between groups . The most frequent grade 3 or 4 adverse events were neutropenia ( nine [ 8 % ] of 117 patients assigned lenalidomide plus prednisone vs 14 [ 13 % ] of 106 allocated lenalidomide alone ) , infection ( eight [ 8 % ] vs five [ 5 % ] ) , and systemic toxicities ( seven [ 6 % ] vs two [ 2 % ] ) . Non-haematological serious adverse events were reported in 13 ( 11 % ) patients assigned lenalidomide plus prednisone versus ten ( 9 % ) allocated lenalidomide alone . Four patients died because of adverse events , three from infections ( two during induction and one during consolidation ) and one because of cardiac toxic effects . INTERPRETATION Consolidation with high-dose melphalan and ASCT remains the preferred option in transplant-eligible patients with multiple myeloma , despite a better toxicity profile with chemotherapy plus lenalidomide . FUNDING Celgene Background High‐dose chemotherapy plus autologous stem‐cell transplantation has been the st and ard treatment for newly diagnosed multiple myeloma in adults up to 65 years of age . However , promising data on the use of combination therapy with lenalidomide , bortezomib , and dexamethasone ( RVD ) in this population have raised questions about the role and timing of transplantation . Methods We r and omly assigned 700 patients with multiple myeloma to receive induction therapy with three cycles of RVD and then consolidation therapy with either five additional cycles of RVD ( 350 patients ) or high‐dose melphalan plus stem‐cell transplantation followed by two additional cycles of RVD ( 350 patients ) . Patients in both groups received maintenance therapy with lenalidomide for 1 year . The primary end point was progression‐free survival . Results Median progression‐free survival was significantly longer in the group that underwent transplantation than in the group that received RVD alone ( 50 months vs. 36 months ; adjusted hazard ratio for disease progression or death , 0.65 ; P<0.001 ) . This benefit was observed across all patient subgroups , including those stratified according to International Staging System stage and cytogenetic risk . The percentage of patients with a complete response was higher in the transplantation group than in the RVD‐alone group ( 59 % vs. 48 % , P=0.03 ) , as was the percentage of patients in whom minimal residual disease was not detected ( 79 % vs. 65 % , P<0.001 ) . Overall survival at 4 years did not differ significantly between the transplantation group and the RVD‐alone group ( 81 % and 82 % , respectively ) . The rate of grade 3 or 4 neutropenia was significantly higher in the transplantation group than in the RVD‐alone group ( 92 % vs. 47 % ) , as were the rates of grade 3 or 4 gastrointestinal disorders ( 28 % vs. 7 % ) and infections ( 20 % vs. 9 % ) . No significant between‐group differences were observed in the rates of treatment‐related deaths , second primary cancers , thromboembolic events , and peripheral neuropathy . Conclusions Among adults with multiple myeloma , RVD therapy plus transplantation was associated with significantly longer progression‐free survival than RVD therapy alone , but overall survival did not differ significantly between the two approaches . ( Supported by Celgene and others ; IFM 2009 Study Clinical Trials.gov number , NCT01191060 . In a r and omized , phase 3 study , superior complete/near-complete response ( CR/nCR ) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone ( VTD ) versus thalidomide-dexamethasone ( TD ) as induction therapy before , and consolidation after , double autologous stem cell transplantation for newly diagnosed myeloma patients ( intention-to-treat analysis ; VTD , n = 236 ; TD , n = 238 ) . This per- protocol analysis ( VTD , n = 160 ; TD , n = 161 ) specifically assessed the efficacy and safety of consolidation with VTD or TD . Before starting consolidation , CR/nCR rates were not significantly different in the VTD ( 63.1 % ) and TD arms ( 54.7 % ) . After consolidation , CR ( 60.6 % vs 46.6 % ) and CR/nCR ( 73.1 % vs 60.9 % ) rates were significantly higher for VTD-treated versus TD-treated patients . VTD consolidation significantly increased CR and CR/nCR rates , but TD did not ( McNemar test ) . With a median follow-up of 30.4 months from start of consolidation , 3-year progression-free survival was significantly longer for the VTD group ( 60 % vs 48 % for TD ) . Grade 2 or 3 peripheral neuropathy ( 8.1 % vs 2.4 % ) was more frequent with VTD ( grade 3 , 0.6 % ) versus TD consolidation . The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation . VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients r and omly assigned to the VTD arm of the study . The study is registered at www . clinical trials.gov as # NCT01134484 The Nordic Myeloma Study Group conducted an open r and omized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation ( ASCT ) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma . Overall , 370 patients were central ly r and omly assigned 3 months after ASCT to receive 20 doses of bortezomib given during 21 weeks or no consolidation . The hypothesis was that consolidation therapy would prolong progression-free survival ( PFS ) . The PFS after r and omization was 27 months for the bortezomib group compared with 20 months for the control group ( P = .05 ) . Fifty-one of 90 patients in the treatment group compared with 32 of 90 controls improved their response after r and omization ( P = .007 ) . No difference in overall survival was seen . Fatigue was reported more commonly by the bortezomib-treated patients in self-reported quality -of-life ( QOL ) question naires , whereas no other major differences in QOL were recorded between the groups . Consolidation therapy seemed to be beneficial for patients not achieving at least a very good partial response ( VGPR ) but not for patients in the ≥ VGPR category at r and omization . Consolidation with bortezomib after ASCT in bortezomib-naive patients improves PFS without interfering with QOL . This trial was registered at www . clinical trials.gov as # NCT00417911 BACKGROUND High-dose chemotherapy with autologous stem-cell transplantation is a st and ard treatment for young patients with multiple myeloma . Residual disease is almost always present after transplantation and is responsible for relapse . This phase 3 , placebo-controlled trial investigated the efficacy of lenalidomide maintenance therapy after transplantation . METHODS We r and omly assigned 614 patients younger than 65 years of age who had nonprogressive disease after first-line transplantation to maintenance treatment with either lenalidomide ( 10 mg per day for the first 3 months , increased to 15 mg if tolerated ) or placebo until relapse . The primary end point was progression-free survival . RESULTS Lenalidomide maintenance therapy improved median progression-free survival ( 41 months , vs. 23 months with placebo ; hazard ratio , 0.50 ; P<0.001 ) . This benefit was observed across all patient subgroups , including those based on the β(2)-microglobulin level , cytogenetic profile , and response after transplantation . With a median follow-up period of 45 months , more than 70 % of patients in both groups were alive at 4 years . The rates of grade 3 or 4 peripheral neuropathy were similar in the two groups . The incidence of second primary cancers was 3.1 per 100 patient-years in the lenalidomide group versus 1.2 per 100 patient-years in the placebo group ( P=0.002 ) . Median event-free survival ( with events that included second primary cancers ) was significantly improved with lenalidomide ( 40 months , vs. 23 months with placebo ; P<0.001 ) . CONCLUSIONS Lenalidomide maintenance after transplantation significantly prolonged progression-free and event-free survival among patients with multiple myeloma . Four years after r and omization , overall survival was similar in the two study groups . ( Funded by the Programme Hospitalier de Recherche Clinique and others ; Clinical Trials.gov number , NCT00430365 . ) PURPOSE The three-drug combination of lenalidomide , bortezomib , and dexamethasone ( RVD ) has shown significant efficacy in multiple myeloma ( MM ) . The Intergroupe Francophone du Myélome ( IFM ) decided to evaluate RVD induction and consolidation therapies in a sequential intensive strategy for previously untreated transplantation-eligible patients with MM . PATIENTS AND METHODS In this phase II study , 31 symptomatic patients age < 65 years were enrolled to receive three RVD induction cycles followed by cyclophosphamide harvest and transplantation . Patients subsequently received two RVD consolidation cycles and 1-year lenalidomide maintenance . RESULTS Very good partial response rate or better at the completion of induction , transplantation , and consolidation therapy was 58 % , 70 % , and 87 % , respectively . Maintenance up grade d responses in 27 % of patients . Overall , 58 % of patients achieved complete response , and 68 % were minimal residual disease ( MRD ) negative by flow cytometry . The most common toxicities with RVD were neurologic and hematologic , including grade 1 to 2 sensory neuropathy ( 55 % ) , grade 3 to 4 neutropenia ( 35 % ) , and thrombocytopenia ( 13 % ) . Two basal cell carcinomas in the same patient and one case of breast cancer were observed . There was no treatment-related mortality . With a median follow-up of 39 months , estimated 3-year progression-free and overall survival were 77 % and 100 % , respectively . None of the patients who achieved MRD negativity relapsed . CONCLUSION The transplantation program with RVD induction and consolidation followed by lenalidomide maintenance produced high- quality responses and showed favorable tolerability in patients with newly diagnosed MM . Overall , 68 % of patients achieved MRD negativity ; none of these patients relapsed . This program is being evaluated in the ongoing IFM/Dana-Farber Cancer Institute 2009 phase III study BACKGROUND The median survival of patients with myeloma after conventional chemotherapy is three years or less . Promising results have been reported with high-dose therapy supported by autologous bone marrow transplantation . We conducted a r and omized study comparing conventional chemotherapy and high-dose therapy . METHODS Two hundred previously untreated patients under the age of 65 years who had myeloma were r and omly assigned at the time of diagnosis to receive either conventional chemotherapy or high-dose therapy and autologous bone marrow transplantation . RESULTS The response rate among the patients who received high-dose therapy was 81 percent ( including complete responses in 22 percent and very good partial responses in 16 percent ) , whereas it was 57 percent ( complete responses in 5 percent and very good partial responses in 9 percent ) in the group treated with conventional chemotherapy ( P < 0.001 ) . The probability of event-free survival for five years was 28 percent in the high-dose group and 10 percent in the conventional-dose group ( P = 0.01 ) ; the overall estimated rate of survival for five years was 52 percent in the high-dose group and 12 percent in the conventional-dose group ( P = 0.03 ) . Treatment-related mortality was similar in the two groups . CONCLUSIONS High-dose therapy combined with transplantation improves the response rate , eventfree survival , and overall survival in patients with myeloma BACKGROUND Data are lacking on whether lenalidomide maintenance therapy prolongs the time to disease progression after autologous hematopoietic stem-cell transplantation in patients with multiple myeloma . METHODS Between April 2005 and July 2009 , we r and omly assigned 460 patients who were younger than 71 years of age and had stable disease or a marginal , partial , or complete response 100 days after undergoing stem-cell transplantation to lenalidomide or placebo , which was administered until disease progression . The starting dose of lenalidomide was 10 mg per day ( range , 5 to 15 ) . RESULTS The study -drug assignments were unblinded in 2009 , when a planned interim analysis showed a significantly longer time to disease progression in the lenalidomide group . At unblinding , 20 % of patients who received lenalidomide and 44 % of patients who received placebo had progressive disease or had died ( P<0.001 ) ; of the remaining 128 patients who received placebo and who did not have progressive disease , 86 crossed over to lenalidomide . At a median follow-up of 34 months , 86 of 231 patients who received lenalidomide ( 37 % ) and 132 of 229 patients who received placebo ( 58 % ) had disease progression or had died . The median time to progression was 46 months in the lenalidomide group and 27 months in the placebo group ( P<0.001 ) . A total of 35 patients who received lenalidomide ( 15 % ) and 53 patients who received placebo ( 23 % ) died ( P=0.03 ) . More grade 3 or 4 hematologic adverse events and grade 3 nonhematologic adverse events occurred in patients who received lenalidomide ( P<0.001 for both comparisons ) . Second primary cancers occurred in 18 patients who received lenalidomide ( 8 % ) and 6 patients who received placebo ( 3 % ) . CONCLUSIONS Lenalidomide maintenance therapy , initiated at day 100 after hematopoietic stem-cell transplantation , was associated with more toxicity and second cancers but a significantly longer time to disease progression and significantly improved overall survival among patients with myeloma . ( Funded by the National Cancer Institute ; Clinical Trials.gov number , NCT00114101 . ) PURPOSE We investigated the effect on minimal residual disease , by qualitative and real-time quantitative polymerase chain reaction ( RQ-PCR ) , of a consolidation regimen that included bortezomib , thalidomide , and dexamethasone ( VTD ) in patients with multiple myeloma ( MM ) responding to autologous stem-cell transplantation ( auto-SCT ) . PATIENTS AND METHODS Patients achieving at least very good partial response who had an available molecular marker based on the immunoglobulin heavy-chain rearrangement received four courses of treatment every month : four infusions per month of bortezomib at 1.6 mg/m(2 ) , thalidomide at 200 mg/d , and dexamethasone at 20 mg/d on days 1 to 4 , 8 to 11 , and 15 to 18 . Patients were studied with tumor-clone-specific primers by qualitative nested PCR and RQ-PCR . Results Of 39 patients enrolled , 31 received the four VTD courses . Immunofixation complete responses increased from 15 % after auto-SCT to 49 % after VTD . Molecular remissions ( MRs ) were 3 % after auto-SCT and 18 % after VTD . Median time to maximum response was 3.5 months . So far , no patient in MR has relapsed ( median follow-up , 42 months ) . VTD consolidation induced an additional depletion of 4.14 natural logarithms of tumor burden by RQ-PCR . Patients with a tumor load less than the median value after VTD had outcomes better than those who had tumor loads above the median value after VTD ( at median follow-up : progression-free survival , 100 % v 57 % ; P < .001 ) . CONCLUSION To the best of our knowledge , this study is the first to document the occurrence of persistent MRs in a proportion of MM patients treated without allogeneic transplantation . Moreover , the major reduction in tumor load recorded by RQ-PCR after VTD suggests that unprecedented levels of tumor cell reduction can be achieved in MM thanks to the new nonchemotherapeutic drugs BACKGROUND We conducted a r and omized trial of the treatment of multiple myeloma with high-dose chemotherapy followed by either one or two successive autologous stem-cell transplantations . METHODS At the time of diagnosis , 399 previously untreated patients under the age of 60 years were r and omly assigned to receive a single or double transplant . RESULTS A complete or a very good partial response was achieved by 42 percent of patients in the single-transplant group and 50 percent of patients in the double-transplant group ( P=0.10 ) . The probability of surviving event-free for seven years after the diagnosis was 10 percent in the single-transplant group and 20 percent in the double-transplant group ( P=0.03 ) . The estimated overall seven-year survival rate was 21 percent in the single-transplant group and 42 percent in the double-transplant group ( P=0.01 ) . Among patients who did not have a very good partial response within three months after one transplantation , the probability of surviving seven years was 11 percent in the single-transplant group and 43 percent in the double-transplant group ( P<0.001 ) . Four factors were significantly related to survival : base-line serum levels of beta2-microglobulin ( P<0.01 ) and lactate dehydrogenase ( P<0.01 ) , age ( P<0.05 ) , and treatment group ( P<0.01 ) . CONCLUSIONS As compared with a single autologous stem-cell transplantation after high-dose chemotherapy , double transplantation improves overall survival among patients with myeloma , especially those who do not have a very good partial response after undergoing one transplantation PURPOSE To evaluate the effect of bortezomib as induction therapy before autologous transplantation , followed by lenalidomide as consolidation-maintenance in myeloma patients . PATIENTS AND METHODS Newly diagnosed patients age 65 to 75 years were eligible . Induction ( bortezomib , doxorubicin , and dexamethasone [ PAD ] ) included four 21-day cycles of bortezomib ( 1.3 mg/m(2 ) on days 1 , 4 , 8 , and 11 ) , pegylated liposomal doxorubicin ( 30 mg/m(2 ) on day 4 ) , and dexamethasone ( 40 mg/d ; cycle 1 : days 1 to 4 , 8 to 11 , and 15 to 18 ; cycles 2 to 4 : days 1 to 4 ) . Autologous transplantation was t and em melphalan 100 mg/m(2 ) ( MEL100 ) and stem-cell support . Consolidation included four 28-day cycles of lenalidomide ( 25 mg/d on days 1 to 21 every 28 days ) plus prednisone ( 50 mg every other day ) , followed by maintenance with lenalidomide ( LP-L ; 10 mg/d on days 1 to 21 ) until relapse . Primary end points were safety ( incidence of grade 3 to 4 adverse events [ AEs ] ) and efficacy ( response rate ) . Results A total of 102 patients were enrolled . In a per- protocol analysis , after PAD , 58 % of patients had very good partial response ( VGPR ) or better , including 13 % with complete response ( CR ) ; after MEL100 , 82 % of patients had at least VGPR and 38 % had CR ; and after LP-L , 86 % of patients had at least VGPR and 66 % had CR . After median follow-up time of 21 months , the 2-year progression-free survival rate was 69 % , and the 2-year overall survival rate was 86 % . During induction , treatment-related mortality was 3 % ; grade 3 to 4 AEs included thrombocytopenia ( 17 % ) , neutropenia ( 10 % ) , peripheral neuropathy ( 16 % ) , and pneumonia ( 10 % ) . During consolidation-maintenance , grade 3 to 4 AEs were neutropenia ( 16 % ) , thrombocytopenia ( 6 % ) , pneumonia ( 5 % ) , and cutaneous rash ( 4 % ) . CONCLUSION Bortezomib as induction before autologous transplantation , followed by lenalidomide as consolidation-maintenance , is an effective regimen BACKGROUND High-dose therapy with supporting autologous stem-cell transplantation remains a controversial treatment for cancer . In multiple myeloma , first-line regimens incorporating high-dose therapy yield higher remission rates than do conventional-dose treatments , but evidence that this translates into improved survival is limited . METHODS In this multicenter study , the Medical Research Council Myeloma VII Trial , we r and omly assigned 407 patients with previously untreated multiple myeloma who were younger than 65 years of age to receive either st and ard conventional-dose combination chemotherapy or high-dose therapy and an autologous stem-cell transplant . RESULTS Among the 401 patients who could be evaluated , the rates of complete response were higher in the intensive-therapy group than in the st and ard-therapy group ( 44 percent vs. 8 percent , P<0.001 ) . The rates of partial response were similar ( 42 percent and 40 percent , respectively ; P=0.72 ) , and the rates of minimal response were lower in the intensive-therapy group than in the st and ard-therapy group ( 3 percent vs. 18 percent , P<0.001 ) . Intention-to-treat analysis showed a higher rate of overall survival ( P=0.04 by the log-rank test ) and progression-free survival ( P<0.001 ) in the intensive-therapy group than in the st and ard-therapy group . As compared with st and ard therapy , intensive treatment increased median survival by almost 1 year ( 54.1 months [ 95 percent confidence interval , 44.9 to 65.2 ] vs. 42.3 months [ 95 percent confidence interval , 33.1 to 51.6 ] ) . There was a trend toward a greater survival benefit in the group of patients with a poor prognosis , as defined by a high beta2-microglobulin level ( more than 8 mg per liter ) . CONCLUSIONS High-dose therapy with autologous stem-cell rescue is an effective first-line treatment for patients with multiple myeloma who are younger than 65 years of age BACKGROUND This open-label , r and omized , phase 3 study compared melphalan at a dose of 200 mg per square meter of body-surface area plus autologous stem-cell transplantation with melphalan-prednisone-lenalidomide ( MPR ) and compared lenalidomide maintenance therapy with no maintenance therapy in patients with newly diagnosed multiple myeloma . METHODS We r and omly assigned 273 patients 65 years of age or younger to high-dose melphalan plus stem-cell transplantation or MPR consolidation therapy after induction , and 251 patients to lenalidomide maintenance therapy or no maintenance therapy . The primary end point was progression-free survival . RESULTS The median follow-up period was 51.2 months . Both progression-free and overall survival were significantly longer with high-dose melphalan plus stem-cell transplantation than with MPR ( median progression-free survival , 43.0 months vs. 22.4 months ; hazard ratio for progression or death , 0.44 ; 95 % confidence interval [ CI ] , 0.32 to 0.61 ; P<0.001 ; and 4-year overall survival , 81.6 % vs. 65.3 % ; hazard ratio for death , 0.55 ; 95 % CI , 0.32 to 0.93 ; P=0.02 ) . Median progression-free survival was significantly longer with lenalidomide maintenance than with no maintenance ( 41.9 months vs. 21.6 months ; hazard ratio for progression or death , 0.47 ; 95 % CI , 0.33 to 0.65 ; P<0.001 ) , but 3-year overall survival was not significantly prolonged ( 88.0 % vs. 79.2 % ; hazard ratio for death , 0.64 ; 95 % CI , 0.36 to 1.15 ; P=0.14 ) . Grade 3 or 4 neutropenia was significantly more frequent with high-dose melphalan than with MPR ( 94.3 % vs. 51.5 % ) , as were gastrointestinal adverse events ( 18.4 % vs. 0 % ) and infections ( 16.3 % vs. 0.8 % ) ; neutropenia and dermatologic toxic effects were more frequent with lenalidomide maintenance than with no maintenance ( 23.3 % vs. 0 % and 4.3 % vs. 0 % , respectively ) . CONCLUSIONS Consolidation therapy with high-dose melphalan plus stem-cell transplantation , as compared with MPR , significantly prolonged progression-free and overall survival among patients with multiple myeloma who were 65 years of age or younger . Lenalidomide maintenance , as compared with no maintenance , significantly prolonged progression-free survival . ( Funded by Celgene ; Clinical Trials.gov number , NCT00551928 . ) |
730 | 19,372,440 | These results suggest no gender difference in outcome among patients treated with intravenous rtPA | BACKGROUND AND PURPOSE The natural history of stroke is worse in women than in men .
Controversial data have been published on the efficacy of thrombolysis with recombinant tissue plasminogen activator ( rtPA ) according to gender .
We evaluated gender differences in the efficacy and safety outcomes of intravenous rtPA using a clinical registry and systematic review . | BACKGROUND AND PURPOSE The feasibility , safety , and efficacy of intravenous tissue plasminogen activator ( t-PA ) for patients with acute ischemic stroke in clinical practice need to be assessed . METHODS We initiated a prospect i ve open-label study at a university hospital and two community hospitals in Houston , Tex , immediately after the publication of the National Institute of Neurological Disorders and Stroke ( NINDS ) t-PA study . A total of 30 patients , age 32 to 90 years , were treated with 0.9 mg/kg of intravenous t-PA ( maximum dose , 90 mg ) within 3 hours of acute ischemic stroke between December 1995 and December 1996 . RESULTS Six percent ( 6 % ) of all patients hospitalized with ischemic stroke received intravenous t-PA at the university hospital and 1.1 % at the community hospitals . The rates of total , symptomatic , and fatal intracerebral hemorrhage were 10 % , 7 % , and 3 % . Thirty-seven percent ( 37 % ) of patients recovered to fully independent function . The average time from stroke onset to emergency department arrival was 57 minutes ; emergency department arrival to computed tomography scan 41 minutes ; and computed tomography scan to administration of treatment 59 minutes . CONCLUSIONS When treatment guidelines are carefully followed in an urban hospital setting , intravenous t-PA for acute ischemic stroke is feasible and shows safety and efficacy comparable to the results of the NINDS study Objective : To study the short and long term differences in outcome between patients ⩾80 years of age and those ⩽79 years of age who received intravenous recombinant tissue plasminogen activator ( iv rt-PA ) for acute stroke within the first 3 hours of symptom onset . Methods : We studied consecutive patients treated with iv rt-PA for acute stroke , with prospect i ve follow up of up to 3 years . Outcome measures included National Institutes of Health Stroke Scale ( NIHSS ) score , Barthel Index ( BI ) , modified Rankin score ( MRS ) , and stroke mortality . Patients were split into two groups : younger ( ⩽79 years ) and older ( ⩾80 years ) . Results : There were 65 patients in the younger cohort and 31 patients in the older . Older patients were more likely to present with more severe baseline stroke ( p = 0.04 ; odds ratio ( OR ) 3.04 ; 95 % confidence interval ( CI ) 1.03 to 8.98 ) . Stroke mortality at 90 days was 10.8 % in the younger and 32.3 % in the older cohort ( p = 0.01 ) . At 90 days ’ follow up , patients in the older cohort with more severe stroke ( NIHSS score ⩾11 ) were nearly 10 times more likely to have poor outcome compared with their younger counterparts presenting with severe stroke ( p = 0.001 ; OR = 10.36 ; 95 % CI 2.16 to 49.20 ) . Baseline stroke severity and age were the only independent and equal predictors for stroke outcome . No threshold was found for age or baseline stroke severity predicting outcome . Conclusion : Older patients presenting with more severe baseline stroke are much less likely to benefit from iv rt-PA as compared with their younger counterparts Background —Intravenous recombinant tissue plasminogen activator ( rtPA ) is an effective therapy for acute ischemic stroke , but it is associated with risk of intracerebral hemorrhage ( ICH ) . Our aim was to identify , in a large cohort of patients , readily available baseline factors that are associated with thrombolysis-related ICH . Methods and Results —In a multicenter retrospective and prospect i ve investigation of individual data from 1205 patients treated in routine clinical practice with intravenous rtPA within 3 hours of stroke symptom onset , 72 patients ( 6 % ) developed symptomatic ICH and 86 additional patients ( 7 % ) had asymptomatic ICH identified on a routine follow-up CT . In analyses based on clinical variables alone , the main attributes associated with ICH were a history of diabetes mellitus and cardiac disease , increasing stroke severity , advancing age , use of antiplatelet agents other than aspirin before stroke onset , and elevated pretreatment mean blood pressure . In additional analyses that incorporated baseline CT and laboratory findings ( in a subset of patients ) , the main associations were early ischemic CT changes , in particular if exceeding one third of middle cerebral artery territory ; increasing stroke severity ; diabetes mellitus or elevated serum glucose ; and lower platelet counts . Final independent attributes associated with parenchymatous hematoma , defined by purely radiologically based criteria , were similar to those of symptomatic ICH . Conclusions —Readily available factors can identify acute ischemic stroke patients at high and low risk for rtPA-related ICH . These factors require confirmation in a prospect i ve cohort before clinical implementation Background and Purpose — Iron overload has been associated with greater oxidative stress and brain injury in experimental cerebral ischemia and reperfusion . This study investigates whether high serum ferritin levels , as an index of increased cellular iron stores , are associated with poor outcome , hemorrhagic transformation , and brain edema after treatment with tissue plasminogen activator in patients with acute ischemic stroke . Methods — A total of 134 consecutive patients treated with intravenous tissue plasminogen activator were prospect ively studied in four centers . Serum ferritin levels were determined at baseline , 24 and 72 hours after treatment . Cranial computed tomography was performed on admission and at 24 to 36 hours after tissue plasminogen activator infusion . Stroke severity and outcome were evaluated by using the National Institute of Health Stroke Scale and the modified Rankin Scale . Results — Computed tomography showed hemorrhagic transformation in 27 patients ( hemorrhagic infa rct ion in 15 and parenchymal hematoma in 12 ; symptomatic in four ) and brain swelling with midline shift in 15 . Poor outcome ( modified Rankin Scale > 2 ) at 90 days was observed in 54.5 % of patients . Ferritin levels at baseline were higher in patients with poor outcome at 90 days ( median [ quartiles ] , 165 [ 98,307 ] versus 17 [ 12,37 ] ng/mL ; P<0.001 ) and in those who developed parenchymal hematoma ( P=0.006 ) , symptomatic hemorrhagic transformation ( P=0.008 ) , and severe brain edema ( P<0.001 ) . Serum ferritin levels higher than 79 ng/mL before tissue plasminogen activator treatment were independently associated with poor outcome ( OR , 117 [ 95 % CI , 25 to 557 ] ) . Conclusions — Increased body iron stores are associated with poor outcome , symptomatic hemorrhagic transformation , and severe edema in patients treated with tissue plasminogen activator after ischemic stroke . These findings suggest that iron overload may offset the beneficial effect of thrombolytic therapies Background and Purpose — Patients with right hemispheric strokes ( RHSs ) present later to an emergency department , have a lower chance to receive intravenous recombinant tissue plasminogen activator ( IV rt-PA ) , and have worse clinical outcomes than do patients with left hemispheric strokes ( LHSs ) . We analyzed outcomes after IV rt-PA with respect to the side of the affected hemisphere . Methods — A prospect i ve cohort of acute stroke patients was treated with IV rt-PA at the London Health Sciences Centre ( December 1998 to March 2003 ) . Differences between patients with RHS and LHS were identified by univariate analysis . Logistic-regression analysis was used to determine a subset of variables independently associated with major neurological improvement at 24 hours and good outcome at 3 months after treatment . Results — Of 219 stroke patients who received IV rt-PA , 165 had hemispheric strokes ( 68 RHSs and 97 LHSs ) . Patients with RHSs were less hypertensive ( P=0.001 ) and had lower pretreatment National Institutes of Health Stroke Scale ( NIHSS ) scores ( P=0.005 ) . LHS ( odds ratio [ OR ] , 2.29 ; 95 % CI , 1.14 to 4.59 ; P=0.019 ) , age ( OR , 0.96 ; 95 % CI , 0.93 to 0.99 ; P=0.012 ) , and pretreatment NIHSS ( OR , 0.83 ; 95 % CI , 0.78 to 0.89 ; P<0.0001 ) were independent predictors of 3-month outcome . Female sex ( OR , 3 ; 95 % CI , 1.53 to 5.90 ; P=0.001 ) and LHS ( OR , 2.07 ; 95 % CI , 1.05 to 4.08 ; P=0.03 ) were independent predictors of major neurological improvement at 24 hours after IV rt-PA . Conclusions — Despite higher pretreatment NIHSS , patients with LHSs have a 2-fold increased chance of a good outcome 3 months after rt-PA treatment compared with patients with RHSs . This gain can be clinical ly detected at 24 hours after treatment . These results need to be coupled with neuroimaging and hemodynamic characteristics known to influence stroke outcome Background and Purpose — The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy ( SITS-MOST ) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with those seen in r and omized , controlled trials ( RCTs ) when used in routine clinical practice within 3 hours of ischemic stroke onset . We aim ed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs . Methods — The study population was SITS-MOST ( n=6483 ) and pooled RCTs ( n=464 ) patients treated with intravenous alteplase within 3 hours of stroke onset . Multivariable , backward stepwise regression analyses ( until P≤0.10 ) were performed to identify the outcome predictors for SITS-MOST . Variables appearing either in the final multivariable model or differing ( P<0.10 ) between SITS-MOST and RCTs were included in the prediction model for the adjustment of outcomes . Main outcome measures were symptomatic intracerebral hemorrhage , defined as National Institutes of Health Stroke Scale deterioration ≥1 within 7 days with any hemorrhage ( RCT definition ) , mortality , and independency as defined by modified Rankin Score of 0 to 2 at 3 months . Results — The adjusted proportion of symptomatic intracerebral hemorrhage for SITS-MOST was 8.5 % ( 95 % CI , 7.9 to 9.0 ) versus 8.6 % ( 6.3 to 11.6 ) for pooled RCTs ; mortality was 15.5 % ( 14.7 to 16.2 ) versus 17.3 % ( 14.1 to 21.1 ) ; and independency was 50.4 % ( 49.6 to 51.2 ) versus 50.1 % ( 44.5 to 54.7 ) , respectively . In the multivariable analysis , older age , high blood glucose , high National Institutes of Health Stroke Scale score , and current infa rct ion on imaging scans were related to poor outcome in all parameters . Systolic blood pressure , atrial fibrillation , and weight were additional predictors of symptomatic intracerebral hemorrhage . Current smokers had a lower rate of symptomatic intracerebral hemorrhage . Disability before current stroke ( modified Rankin Score 2 to 5 ) , diastolic blood pressure , antiplatelet other than aspirin , congestive heart failure , patients treated in new centers , and male sex were related to high mortality at 3 months . Conclusions — The adjusted outcomes from SITS-MOST were almost identical to those in relevant RCTs and reinforce the conclusion drawn previously in the unadjusted analysis . We identified several important outcome predictors to better identify patients suitable for thrombolysis Background : Predictors of outcome and safety in intravenous thrombolysis within 3 h in clinical routine is a matter of ongoing debate . Available reports contain small patient numbers or summarize heterogeneous multicenter data . Methods : Four hundred and fifty patients received intravenous thrombolysis within 3 h after stroke . Pretreatment NIHSS score and detailed medical history were analyzed . Noncontrast CT was performed before thrombolysis , 24–36 h later and in case of clinical deterioration . Symptomatic intracranial hemorrhage ( SICH ; any bleeding with an NIHSS increase of ≧4 points ) and clinical outcome ( modified Rankin Scale , mRS ) after 3 months were recorded . Logistic regression identified parameters predictive of independence ( mRS 0–2 ) and SICH . Results : Median onset to admission , door to needle and onset to treatment time was 75 , 50 and 135 min , respectively . Direct presentation by emergency service ( 64 % ) was the fastest way of referral . Median pretreatment NIHSS was 11 points . Independence ( mRS 0–2 ) was reached by 53 % . Mortality was 11 % ( 7 % intracerebral , 4 % extracerebral complications ) . Logistic regression identified low NIHSS , low age and absent diabetes as predictors of independence . Overall hemorrhagic complications and SICH were found in 18 and 4 % of the patients , respectively . Extracerebral bleeding complications and allergic reactions were found in 3 and 1 % , respectively . Conclusion : This largest single center report presents a sample in the range of the 3 h rt-PA cohort of all r and omized controlled trials . Outcome was comparable to r and omized studies with a higher rate of independence and a lower rate of mortality and SICH CONTEXT The focus of thrombolytic therapy in acute stroke has been on favorable outcome at 3 months . Few studies have analyzed outcome at 24 hours . An early and reliable prediction of poor outcome has implication s for clinical management and discharge planning . OBJECTIVE To evaluate predictors of lack of improvement at 24 hours after receiving alteplase and their relationship with poor outcome at 3 months . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort of consecutive patients with acute stroke who received alteplase and were admitted to a university hospital from January 1999 to March 2003 . Participants were recruited from 2 academic centers in a major city in Ontario and 33 affiliated hospitals from 7 counties . MAIN OUTCOME MEASURES Lack of improvement defined as a difference between the National Institutes of Health Stroke Scale score at baseline and at 24 hours of 3 points or less . Poor outcome at 3 months defined by a modified Rankin Scale score of 3 to 5 or death . RESULTS Among 216 patients with acute stroke who were treated with alteplase , 111 ( 51.4 % ) had a lack of improvement at 24 hours . After adjusting for age , sex , and stroke severity , baseline glucose level on admission ( odds ratio [ OR ] 2.89 ; 95 % confidence interval [ CI ] , 1.40 - 5.99 for a glucose level > 144 mg/dL [ > 8 mmol/L ] ) , cortical involvement ( OR , 2.66 ; 95 % CI , 1.36 - 5.20 ) , and time to treatment ( OR , 1.01 ; 95 % CI , 1.0 - 1.02 for each 1 minute increase in time to treatment ) were independent predictors of lack of improvement . At 3 months , 43 patients ( 20.2 % ) had died ; of the 170 survivors , 75 patients ( 44 % ) had poor outcomes . After adjusting for age , sex , and stroke severity , lack of improvement at 24 hours was an independent predictor of poor outcome ( OR , 12.9 ; 95%CI , 5.7 - 29.6 ) and death ( OR , 7.5 ; 95 % CI , 2.9 - 19.6 ) . Patients with a lack of improvement had longer lengths of hospitalization ( 14.5 vs 9.6 days ; P = .02 ) . CONCLUSIONS Among patients with acute stroke treated with thrombolytic therapy , lack of improvement at 24 hours is associated with poor outcome and death at 3 months . Elevated glucose level , time to thrombolytic therapy , and cortical involvement were predictors of lack of improvement This data bank-based , multicenter study compared all stroke patients with IV tissue plasminogen activator aged ≥80 years ( n = 38 ) and those < 80 years old ( n = 287 ) . Three-month mortality was higher in older patients . Favorable outcome ( modified Rankin scale ≤1 ) and intracranial hemorrhage ( asymptomatic/symptomatic/fatal ) were similarly frequent in both groups . Logistic regression showed that stroke severity , time to thrombolysis , glucose level , and history of coronary heart disease independently predicted outcome , whereas age did not BACKGROUND AND PURPOSE Although new , large , double-blind , r and omized studies are needed to establish the efficiency of intravenous thrombolysis , open trials of sufficient size may also provide novel data concerning specific outcomes after thrombolysis . METHODS An open study of intravenous rtPA in 100 patients with internal carotid artery ( ICA ) territory strokes between 20 and 81 years of age , with a baseline Sc and inavian Stroke Scale ( SSS ) score of < 48 at entry was conducted . Inclusion time was within 7 hours after stroke onset . rtPA ( 0.8 mg/kg ) was infused for 90 minutes , with an initial 10 % bolus . Heparin was given according to 3 consecutive protocol s. The SSS evaluation was done on days 0 , 1 , 7 , 30 , and 90 . CT scan was performed before treatment , on days 1 and 7 . Etiological investigations included echocardiography and carotid Doppler sonography and /or angiography . Outcome at 1 year was documented by SSS score , the modified Rankin Scale ( mRS ) score , and a 10-point invalidity scale . Multivariate logistic regression was used to identify predictors of poor versus good outcome . RESULTS At day 90 , 45 patients ( 45 % ) had a good result , defined as complete regression or slight neurological sequelae ( mRS score of 0 - 1 ) , 18 patients had a moderate outcome ( mRS 2 - 3 ) , and 31 patients had serious neurological sequelae ( mRS 4 - 5 ) . Six patients died , 2 with intracerebral hematoma after immediate heparin . Five of 11 patients ( 45.5 % ) treated between 6 and 7 hours had a good result . The overall intracerebral hematoma rate was 7 % . Higher values of fibrin degradation products at 2 hours were observed in the subgroup with intracerebral hematomas . Significant predictors of poor outcome on multivariate logistic regression analysis were baseline SSS score of < 15 ( odds ratio [ OR ] , 3.38 ; 95 % confidence interval [ CI ] , 1.07 to 10 . 74 ; P=0.04 ) , indistinction between white and gray matter on CT scan ( OR , 6.59 ; 95 % CI , 2.19 to 19.79 ; P=0.0008 ) , and proximal internal carotid thrombosis ( OR , 3.29 ; 95 % CI , 0.99 to 10.95 ; P=0.05 ) . CONCLUSIONS Our study confirms the safety of intravenous rtPA at a dose of 0.8 mg/kg and suggests efficacy for this drug even within 7 hours . Outcome and hematoma rates were at least as favorable as for trials of therapy with a 3-hour time window . Subgroups with a poor prognosis include low baseline neurological score , baseline CT changes , and proximal ICA thrombosis . However , approximately 30 % of patients with each of these characteristics show a good outcome , so their inclusion in future routine rtPA protocol s is still justified Background and Purpose — Previous reports suggest that women achieve better outcome than men after intravenous thrombolysis for ischemic stroke . Coagulation and fibrinolysis differ between sexes . These findings prompted us to investigate possible gender differences in arterial recanalization after intravenous tissue plasminogen activator ( IV tPA ) . Methods — We identified 100 consecutive patients who presented with acute ischemic stroke and received IV tPA within 6 hours of onset . Only patients with large artery anterior circulation strokes , as determined by MRI/MRA or CT/CTA before treatment , who had follow-up vascular study within 72 hour after treatment were included . We compared demographics , clinical features , admission medications , symptom-to-needle and treatment-to-repeat vascular imaging times , baseline National Institutes of Health Stroke Severity score , radiological and laboratory data , stroke mechanism , and outcome between the sexes . Results — 39 patients met all inclusion /exclusion criteria ( 22 men and 17 women ) . The recanalization rate was significantly higher in women ( 94 % versus 59 % ; P=0.02 ) . This difference remained statistically significant after excluding patients whose strokes were attributed to internal carotid artery occlusive lesions , and when the analysis was limited to those treated within 3 hours of stroke onset . All other confounding variables did not differ significantly between the sexes . Conclusions — In our cohort , vascular occlusive lesions were more likely to recanalize in women than men in response to IV tPA . These preliminary findings need to be vali date d in larger prospect i ve studies Background — We assessed the incidence of early recurrent ischemic stroke in stroke patients treated with intravenous tissue-type plasminogen activator ( tPA ) and the temporal pattern of its occurrence compared with symptomatic intracranial hemorrhage ( ICH ) . Methods and Results — Prospect ively collected , population -based data for 341 consecutive acute stroke patients ( 62 % men ; mean age , 66 years ) treated with tPA according to the National Institute of Neurological Disorders and Stroke study protocol at 8 medical centers in Switzerl and ( 3 academic and 5 community ) between January 2001 and November 2004 were retrospectively analyzed . The primary outcome measure was neurological deterioration ≥4 points on the National Institutes of Health Stroke Scale occurring within 24 hours of tPA treatment and caused either by recurrent ischemic stroke ( defined as the occurrence of new neurological symptoms suggesting involvement of initially unaffected vascular territories and evidence of corresponding ischemic lesions on cranial computed tomography scans , in the absence of ICH ) or by ICH . Early recurrent ischemic stroke was diagnosed in 2 patients ( 0.59 % ; 95 % confidence interval , 0.07 % to 2.10 % ) and symptomatic ICH in 15 patients ( 4.40 % ; 95 % confidence interval , 2.48 % to 7.15 % ) . Both recurrent ischemic strokes occurred during thrombolysis , whereas symptomatic ICHs occurred 2 to 22 hours after termination of tPA infusion . Conclusions — Recurrent ischemic stroke is a rare cause of early neurological deterioration in acute stroke patients undergoing intravenous thrombolysis , with a different temporal pattern compared with that of symptomatic ICH Objective : To determine the association between sex and functional outcomes after thrombolytic treatment for acute ischemic stroke in the context of a clinical trial . Methods : We analyzed predictors of outcome among patients treated with recombinant tissue plasminogen activator ( rtPA ) in the Glycine Antagonist in Neuroprotection for Patients with Acute Stroke Americas trial , a multicenter , r and omized , double-blind , placebo-controlled study of a putative neuroprotectant . Results : Among 1,367 trial patients , 333 ( 24 % ) were treated with rtPA within 3 hours . The proportion of patients achieving good functional outcomes at 3 months differed by sex ( 47.5 % of men vs 30.3 % of women had Barthel Index [ BI ] ≥ 95 ; 32.2 % of men vs 23.4 % of women had modified Rankin Score [ mRS ] ≤ 1 ) . NIH Stroke Score was similar by sex . Men were more likely to have good functional outcomes after adjusting for relevant covariates : for BI ≥ 95 , adjusted odds ratio ( OR ) 3.28 ( 1.74 to 6.17 ) ; for mRS ≤ 1 , adjusted OR 2.12 ( 1.11 to 4.03 ) . Survival was worse among men : adjusted OR 0.45 ( 0.20 to 1.01 ) . Other predictors of functional outcomes included age , stroke side , severity , complications , and infections . Conclusions : Among tissue plasminogen activator-treated patients in this clinical trial population , men were approximately three times as likely to have good functional outcomes , despite elevated mortality . Thrombolysis for stroke may not reverse the tendency for women to have worse functional outcomes after stroke CONTEXT Data are limited regarding the risks and benefits of thrombolytic therapy for acute ischemic stroke outside of clinical trials . OBJECTIVE To investigate predictors of in-hospital mortality in patients with ischemic stroke treated with intravenous tissue plasminogen activator ( tPA ) within a pooled analysis of large German stroke registers . DESIGN AND SETTING Prospect i ve , observational cohort study conducted at 225 community and academic hospitals throughout Germany cooperating within the German Stroke Registers Study Group . PATIENTS A total of 1658 patients with acute ischemic stroke who were admitted to study hospitals between 2000 and 2002 and were treated with tPA . MAIN OUTCOME MEASURE In-hospital mortality . RESULTS One hundred sixty-six patients ( 10 % ) who received tPA died during hospitalization , with 67.5 % of these deaths occurring within 7 days . Factors predicting in-hospital death after tPA use were older age ( for each 10-year increment in age , adjusted odds ratio [ OR ] , 1.6 ; 95 % confidence interval [ CI ] , 1.3 - 1.9 ) and altered level of consciousness ( adjusted OR , 3.4 ; 95 % CI , 2.4 - 4.7 ) . The overall rate of symptomatic intracranial hemorrhage was 7.1 % and increased with age . One or more serious complications was observed in 27.2 % of all patients and in 83.9 % of patients who died after tPA treatment . An inverse relation between the number of patients treated with tPA in the respective hospital and the risk of in-hospital death was observed ( adjusted OR , 0.97 ; 95 % CI , 0.96 - 0.99 for each additional patient treated with tPA per year ) . CONCLUSION In patients with ischemic stroke who are treated with tPA , disturbances of consciousness and increasing age are associated with increased in-hospital mortality Background : Major neurologic improvement at 24 hours after administration of recombinant tissue plasminogen activator ( rt-PA ) in acute stroke may predict good outcome at 3 months . Objective : To identify predictors of major neurologic improvement at 24 hours after IV rt-PA administration and its relationship with outcome at 3 months . Methods : The authors analyzed patients with acute stroke treated with IV rt-PA from two academic centers in London , Ontario , and 33 affiliated hospitals between 1999 and 2003 . Major neurologic improvement was defined by a ≥8-point improvement in NIH Stroke Scale ( NIHSS ) score or an NIHSS score of 0 or 1 at 24 hours . Good outcome was defined as a 3-month modified Rankin Scale of 0 to 1 . Results : Of 219 patients with acute stroke treated with rt-PA , 61 ( 28 % ) had major neurologic improvement at 24 hours . Glucose levels < 8 mmol/L ( OR 4.98 , 95 % CI 1.6 to 15.2 ) , lack of cortical involvement on 24 hour CT scan ( OR 3.97 , 95 % CI 1.87 to 8.43 ) , and female sex ( OR 2.4 , 95 % CI 1.12 to 5.13 ) were associated with major neurologic improvement after adjusting for covariates . Patients with major neurologic improvement had a shorter hospital stay ( 6.7 vs 14.3 days ; p = 0.001 ) . Major neurologic improvement was an independent predictor of good outcome at 3 months ( OR 12.8 , 95 % CI 4.72 to 34.6 ) . Conclusions : Major neurologic improvement after rt-PA was observed in 28 % of patients and independently predicted good outcome at 3 months . Female sex , glucose levels < 8 mmol/L , and absence of cortical involvement at 24 hours CT scan were associated with major neurologic improvement BACKGROUND There is some uncertainty whether prior use of antiplatelet ( AP ) drugs increases the risk of symptomatic intracerebral hemorrhage ( SICH ) and influences functional outcome in patients with ischemic stroke treated with intravenous thrombolysis . OBJECTIVE To assess whether prior use of AP drugs is related to outcome following intravenous tissue plasminogen activator therapy in patients with ischemic stroke . DESIGN , SETTING , AND PATIENTS A single-center prospect i ve observational cohort study of the relation between prior AP therapy , occurrence of SICH , and functional outcome of consecutive patients with ischemic stroke undergoing intravenous thrombolysis with tissue plasminogen activator in a university hospital between April 1 , 2002 , and November 30 , 2006 . MAIN OUTCOME MEASURES The occurrence of SICH and favorable outcome reflecting independence defined as a modified Rankin Scale score of 2 or lower at 3 months . RESULTS Of the 301 patients who received intravenous tissue plasminogen activator , 89 used AP drugs prior to thrombolysis . Symptomatic intracerebral hemorrhage occurred in 12 patients ( 13.5 % ; 95 % confidence interval , 7.8%-22.3 % ) who had received AP drugs and in 6 patients ( 2.8 % ; 95 % confidence interval , 1.2%-6.2 % ) without prior AP therapy ( P = .001 ) . Multivariate analysis revealed that prior AP therapy was an independent predictor of SICH ( odds ratio , 6.0 ; 95 % confidence interval , 2.0 - 17.1 ) . Nonetheless , prior AP therapy was independently associated with a favorable outcome ( odds ratio , 2.0 ; 95 % confidence interval , 1.0 - 4.3 ) . CONCLUSION Despite a higher incidence of SICH , the net benefit of intravenous tissue plasminogen activator therapy for acute ischemic stroke was greater in patients using AP drugs The use of rtPA in stroke patients aged > 80 years remains controversial and it is debated whether there are sex-based differences in the response to rtPA . We assessed the clinical value of thrombolytic therapy in patients aged > 80 years ( elderly group ) in comparison with a non-elderly group , and evaluated the existence of sex differences in the response to rtPA . All consecutive patients ( n = 157 ) treated with rtPA were prospect ively assessed since July 2001 , including 49 elderly patients who fulfilled the National Institute of Neurological Disorders and Stroke ( NINDS ) criteria . Changes of the National Institute of Health Stroke Scale ( NIHSS ) score at 1 h , 24 h , and 7 days after rtPA administration , favourable outcome at day 90 [ ( modified Rankin Scale ) mRS 0 - 1 , or 2 if mRS = 2 before the stroke ] , symptomatic bleedings , and death rates were compared between elderly and non-elderly patients . Using logistic regression , baseline NIHSS score [ odds ratio ( OR ) 0.59 , 95 % confidence interval ( CI ) 0.41 - 0.84 ] was an independent predictor of favourable outcome , but not sex ( OR 0.72 , 95 % CI 0.33 - 1.56 ) , or age > 80 years ( OR 0.74 , 95 % CI 0.32 - 1.70 ) . The rates of clinical improvement , mortality , or symptomatic CNS bleeding were also unrelated to age and sex . In conclusion , the response to IV rtPA is not impaired in elderly stroke patients and male and female are equally responsive Aim : We sought to determine whether there were differences between men and women with acute stroke in their baseline characteristics and outcome in a large cohort of patients r and omized in the International Stroke Trial ( IST ) . Methods : Of the 19,435 patients r and omized in the IST , 17,370 had an ischemic stroke confirmed by CT scan or autopsy ( 8,003 female and 9,367 male ) . In males and females , we compared baseline characteristics ( age , frequency of atrial fibrillation , pre-stroke administration of aspirin and systolic blood pressure , conscious level , stroke syndrome ) and outcome at 14 days and 6 months ( death , complications , dependency , recovery , place of residence ) . We developed a specific logistic regression model to adjust for case-mix in order to evaluate the separate influence of gender on outcome . Results : Female patients were older , suffered more frequently from atrial fibrillation , had higher systolic blood pressure at r and omization and generally had more severe strokes ( a higher proportion were unconscious or drowsy or had a total anterior circulation syndrome ) . Females had higher 14-day and 6-month case fatality and were more likely to be dead or dependent at six months ( and consequently more likely to require institutional or residential care ) . Gender was an independent predictor of death or dependency at 6 months . Conclusions : The adverse effect of female gender on outcome indicates that further research to explore the underlying biological mechanism is justified , and that more intensive acute and long-term treatment may be needed to improve outcome among female patients with stroke Background : Large studies of patients with acute stroke not receiving thrombolytic therapy have repeatedly demonstrated poorer outcomes for women compared to men . An analysis of five pooled r and omized controlled trials testing IV recombinant tissue plasminogen activator ( rtPA ) demonstrated that rtPA benefits women more than men ; the usual gender difference , apparent among controls , was totally nullified in the rtPA group . This nullification of the usual gender effect among rtPA-treated patients has not been confirmed . Methods : We analyzed baseline characteristics and functional outcomes in men vs women in the Canadian Alteplase for Stroke Effectiveness Study ( CASES ) , a multicenter study that collected outcomes data for patients treated with rtPA in Canada to assess the safety and effectiveness of alteplase for stroke in the context of routine care . Results : Among 1,110 patients , including 615 men and 505 women , a normal or near normal outcome at 90 days was found in 37.1 % of men vs 36.0 % of women ( p = 0.71 ) . This was essentially unchanged after adjusting for differences in baseline characteristics , including age > 70 , glucose , hypertension , atrial fibrillation , hypercholesterolemia , baseline National Institute of Health Stroke Severity , and baseline Alberta Stroke Program Early CT score ( 35.2 % in men vs 38.2 % in women , p = 0.332 ) . Ninety-day mortality was similar between the sexes in both the adjusted and unadjusted analysis . Conclusions : There was no difference in 90-day outcomes in recombinant tissue plasminogen activator (rtPA)-treated men and rtPA-treated women . This is consistent with the pooled analysis of r and omized controlled trials , showing greater benefit for thrombolysis in women and nullification of the usual gender difference in outcome . GLOSSARY : ASPECT = Alberta Stroke Program Early CT ; CASES = Canadian Alteplase for Stroke Effectiveness Study ; LACS = lacunar stroke ; MAP = mean arterial pressure ; mRS = modified Rankin Score ; NIHSS = National Institute of Health Stroke Severity ; OCSP = Oxfordshire Community Stroke Project ; PACS = partial anterior circulation stroke ; POCS = posterior circulation stroke ; rtPA = recombinant tissue plasminogen activator ; sICH = symptomatic intracerebral hemorrhage ; TACS = total anterior circulation stroke |
731 | 19,948,418 | Studies so far suggest a protective role for diabetes on the development of AAA . | OBJECTIVE The aim of this review is to delineate the association between abdominal aortic aneurysms ( AAAs ) and diabetes mellitus .
Mechanisms for the underlying association are then discussed . | Background —Markers of systemic inflammation ( eg , C-reactive protein [ CRP ] and interleukin-6 [ IL-6 ] ) have been proposed to be “ nontraditional ” risk factors for cardiovascular disease in patients with type 2 diabetes mellitus . Matrix metalloproteinase-9 ( MMP-9 ) has been implicated in the pathogenesis of atherosclerotic plaque rupture , which raises the possibility of the use of MMP-9 levels as a marker for future myocardial infa rct ion or unstable angina . In vitro and animal studies suggest that thiazolidinediones can reduce the expression of these markers . The purpose of this analysis was to determine whether rosiglitazone alters serum concentrations of CRP , IL-6 , MMP-9 , and white blood cell count ( WBC ) and to examine the relationship of these effects with demographic and disease variables . Methods and Results —CRP , IL-6 , MMP-9 , and WBC were analyzed from stored frozen serum sample s obtained from patients with type 2 diabetes who completed a 26-week r and omized , double-blind , placebo-controlled study . After 26 weeks of rosiglitazone treatment , the percentage reductions in mean CRP , MMP-9 , and WBC levels were statistically significant compared with baseline and placebo ( P < 0.01 ) . The percentage reduction in mean IL-6 was small and similar in the rosiglitazone and placebo groups . The change in each inflammatory marker from baseline to week 26 was significantly correlated ( P < 0.05 ) with each of the other markers , as well as with the homeostasis model assessment estimate of insulin resistance . Conclusions —Rosiglitazone reduces serum levels of MMP-9 and the proinflammatory marker CRP in patients with type 2 diabetes , which indicates potentially beneficial effects on overall cardiovascular risk Ramipril improves cardiovascular outcome in patients with peripheral arterial disease ; however , the precise mechanisms of benefit remain to be eluci date d. The effect of ramipril on large-artery stiffness in patients with peripheral arterial disease was examined . In addition , we determined the effect of ramiprilat on extracellular matrix from human aortic smooth muscle cell culture . Forty patients with peripheral arterial disease were r and omized to receive ramipril , 10 mg once daily or placebo for 24 weeks . Arterial stiffness was assessed globally via systemic arterial compliance and augmentation index ( carotid tonometry and Doppler velocimetry ) , and regionally via carotid – femoral pulse wave velocity . Angiotensin-converting enzyme inhibition increased arterial compliance by 0.10±0.02 mL/mm Hg , ( P<0.001 , all probability values relative to placebo ) and reduced pulse wave velocity by 1.7±0.2 m/s ( P<0.001 ) , augmentation index by 4.1±0.3 % ( P<0.001 ) , and systolic blood pressure by 5±1 mm Hg ( P<0.001 ) . Ramipril did not reduce mean arterial pressure significantly compared with placebo ( P=0.59 ) . In cell culture , ramiprilat decreased collagen deposition by > 50 % and increased elastin and fibrillin-1 deposition by > 3- and 4-fold respectively ( histochemistry and immunohistochemistry ) . Fibrillin-1 gene expression was increased 5-fold ( real-time reverse-transcriptase polymerase chain reaction ) . Ramiprilat also reduced gene and protein ( Western ) expression of both matrix metalloproteinase (MMP)-2 and MMP-3 . In conclusion , ramipril promoted an elastogenic matrix profile that may contribute to the observed clinical reduction in large-artery stiffness and carotid pressure augmentation , which occurred independently of mean arterial blood pressure reduction in patients with peripheral arterial disease PURPOSE Early repair of abdominal aortic aneurysms ( AAA ) is particularly appropriate for those that are most likely to exp and . Our aim was to define features on computed tomography ( CT ) scanning associated with subsequent rapid aneurysm expansion . METHODS We review ed CT scans of 80 patients with AAA ( > 3.0 cm ) who underwent CT scanning of the abdomen and pelvis two times , at least 6 months apart , between 1986 and 1992 . The aneurysms initially measured 4.4 + /- 0.6 cm , and the mean interval between obtaining scans was 22 + /- 12 months . Clinical variables assessed included age , sex , medical risk factors , underlying cardiovascular and pulmonary diseases , and administration of beta blockers and lipid-lowering agents . Computer-aided measurements on each CT scan section included the maximal and minimal diameters and area of the aneurysm . Dimensions of the luminal thrombus and the arc of aneurysm wall covered by thrombus ( TARC ) . Maximal aneurysm dimensions were related to juxtarenal aortic and second lumbar vertebral body dimensions . RESULTS Mean aneurysm expansion was 0.26 + /- 0.25 cm/yr . CT scanning variables that correlated significantly with rate of expansion included the mean TARC ( r = 0.43 , p < 0.001 ) , thrombus volume fraction ( r = 0.37 , p < 0.001 ) , TARC on the largest aneurysm cross section ( r = 0.34 , p < 0.01 ) , and thrombus area fraction ( r = 0.30 , p < 0.01 ) . Rapid expansion ( > 0.5 cm/yr ) occurred in 15 ( 19 % ) aneurysms . The two predictors for rapid expansion on logistic regression analysis were mean TARC ( p < 0.005 ) and the presence of carotid artery disease ( p < 0.05 ) . CONCLUSION An increased AAA thrombus load is associated with a higher likelihood of rapid expansion and should weigh in favor of early surgical repair BACKGROUND Angiotensin-converting enzyme ( ACE ) inhibitors prevent the expansion and rupture of aortic aneurysms in animals . We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms . METHODS We did a population -based case-control study of linked administrative data bases in Ontario , Canada . The sample included consecutive patients older than 65 ( n=15,326 ) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1 , 1992 , and April 1 , 2002 . FINDINGS Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm ( odds ratio [ OR ] 0.82 , 95 % CI 0.74 - 0.90 ) than those who did not receive ACE inhibitors . Adjustment for demographic characteristics , risk factors for rupture , comorbidities , contraindications to ACE inhibitors , measures of health-care use , and aneurysm screening yielded similar results ( 0.83 , 0.73 - 0.95 ) . Consistent findings were noted in subgroups at high risk of rupture , including patients older than 75 years and those with a history of hypertension . Conversely , such protective associations were not observed for beta blockers ( 1.02 , 0.89 - 1.17 ) , calcium channel blockers ( 1.01 , 0.89 - 1.14 ) , alpha blockers ( 1.15 , 0.86 - 1.54 ) , angiotensin receptor blockers ( 1.24 , 0.71 - 2.18 ) , or thiazide diuretics ( 0.91 , 0.78 - 1.07 ) . INTERPRETATION ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm , unlike other antihypertensive agents . R and omised trials of ACE inhibitors for prevention of aortic rupture might be warranted Aortic aneurysm is the 10th leading cause of death in older men [ 1 ] , but fundamental issues about the cause and epidemiology of this condition remain unresolved . A fourfold variation in the prevalence of abdominal aortic aneurysm ( AAA ) has been seen among participants in screening programs [ 2 ] , and the traditional view that AAA is a manifestation of atherosclerosis has been challenged by recent studies that suggest a role for specific genetic factors [ 3 ] . Most information on the epidemiology of AAA has come from screening studies [ 4 - 10 ] . However , the studies that have reported on potential risk factors have screened fewer than 5500 patients each , result ing in too few cases for multivariable analysis . Two nested casecontrol studies have reported multiple risk factor analyses for aortic aneurysms [ 11 , 12 ] , but these studies were also relatively small ( one contained 41 and one contained 165 aneurysms ) , did not attempt to identify all cases of AAA in their study population s , did not consider such important factors as family history of AAA , and disagreed about the significance of such factors as height and serum cholesterol levels . To identify factors that are independently associated with AAA and to determine the prevalence of previously unrecognized AAA in defined demographic and risk groups , we collected and analyzed self-reported information from a large cohort of veterans who participated in a multicenter ultrasonographic screening program . Methods Participants The Aneurysm Detection and Management ( ADAM ) study is an ongoing r and omized clinical trial comparing two strategies for the management of AAA ( immediate surgery and surgery reserved for aneurysms that enlarge to 5.5 cm , enlarge rapidly , or cause symptoms ) in patients 50 to 79 years of age with asymptomatic AAAs 4.0 to 5.4 cm in diameter [ 13 ] . Ultrasonography screening clinics were established at the 15 participating Department of Veterans Affairs medical centers to support recruitment into the trial . Active patients at these centers ( that is , patients treated during the current or previous fiscal year and those who had future appointments ) who met the age criteria for the study were invited by mail to attend the clinic . Throughout the screening period , the letters were mailed in batches according to patient social security number using the continuously up date d administrative patient data at each participating center . A second mailing that was done at some centers excluded persons who had previously been seen in the screening clinic . Active patients at the participating centers were also accepted for screening on a walk-in basis ; patients 50 to 79 years of age were included in the analysis because they were members of the target population and eventually would have been invited to participate . Inadvertent repeated screenings were identified by patient social security number , and results of second screenings were excluded . Patients who reported previously having been told that they had an AAA were also excluded . We include data from patients who were screened from the beginning of the program in October 1992 through March 1995 . The study was approved by the human rights committee at the Veterans Affairs Cooperative Studies Program coordinating center and by the institutional review boards at the 15 participating centers . Assessment of Associated Factors Before ultrasonographic examination , all patients completed a brief question naire that asked about demographic information and possible risk factors for AAA . Patients were asked whether they had ever been told by a physician that they had the condition in question ( for example , high blood pressure ) . The question naire was developed for the study , tested at the participating centers , and revised accordingly before the study began . The reliability of the data from the self-reported question naire was assessed by comparing this data with data collected in the subset of screened patients who had an AAA and who were later included in the clinical trial . These data were recorded by a study nurse after discussion with the patient and review of the patient 's medical records . Ascertainment of Abdominal Aortic Aneurysm The abdominal aorta was measured above and below the renal arteries using a 3.5-MHz real-time sector scanner . The ultrasonographers were instructed to 1 ) scan the aorta in the anteroposterior and lateral planes and 2 ) report the maximum external diameter at the widest point of any dilatation for the suprarenal and infrarenal segments . The ultrasonographers met twice during the study period to review techniques and compare measurement distributions . Patients found to have an AAA or another suspected abnormality were referred for evaluation , and discrepancies between the results of subsequent testing and the results of the initial screening were reported back to the study ultrasonographer . Screening appointments for patients whose examinations were inadequate because of insufficient fasting were rescheduled . An infrarenal aortic diameter of 4.0 cm or larger is generally agreed to constitute AAA , but no method for defining a smaller AAA has gained wide acceptance [ 14 ] . Most investigators have used unadjusted aortic diameter ( with such cutoff points as 3.0 cm , which is known to be associated with risk for rupture [ 15 ] ) but this practice may exaggerate the prevalence of AAA in larger people . To avoid this problem , use of a ratio of infrarenal aortic diameter to suprarenal aortic diameter of 1.5 or greater has been proposed [ 14 ] . However , this method labels some small aortas as having an AAA and fails to account for aneurysmal dilatation of the suprarenal aorta . The latter problem has , in turn , been addressed by a proposal to define AAA as an aortic diameter more than 1.5 times the diameter that would be expected on the basis of age , sex , body size , and other factors . However , values for the expected diameter have not been well defined [ 14 ] . Therefore , we considered several definitions of AAA , including an infrarenal aortic diameter of at least 3.0 cm , a diameter of at least 4.0 cm , and a ratio of infrarenal to suprarenal aortic diameter of 1.5 or greater . Statistical Analysis Analyses to determine the association between the items on the question naire and the presence of AAA were done using univariable and multivariable logistic regression . Because the purpose of the analysis was descriptive , the multivariable models included all variables that were considered in the question naire . Composite variables were formed from several questions that were used to identify coronary artery disease ; hypertension ; hypercholesterolemia ; and , in a separate analysis , any atherosclerosis . Responses of do n't know were treated as responses of no for specific diseases under the assumption that if a person had a disease , he or she would be aware of it . This assumption was not made for hypercholesterolemia or hypertension , which are often asymptomatic ; responses of do n't know for these conditions were considered to be missing . Because of the result ing large number of missing responses for hypercholesterolemia , an indicator variable was included for this item to prevent deletion of these patients from the logistic models ( as was otherwise done for missing responses ) [ 16 ] . Extreme values for height ( < 152 cm and > 198 cm ) , weight ( < 45 kg and > 182 kg ) , waist circumference ( < 56 cm and > 152 cm ) , and cholesterol levels ( < 2.59 mmol/L and > 12.93 mmol/L ) and smoking history incompatible with age were also excluded . To compare the many cases of smaller , borderline AAA with cases of larger , definite AAA , separate regression models were developed 1 ) for comparing patients who had AAAs of 3.0 to 3.9 cm with those who had infrarenal aortic diameters less than 3.0 cm and 2 ) for comparing those who had AAAs of 4.0 cm or larger with those who had infrarenal aortic diameters less than 3.0 cm . A third model was developed for comparing patients whose ratio of infrarenal to suprarenal aortic diameter was 1.5 or greater with those whose ratio was less than 1.5 . Comparison of question naire data with data collected for the clinical trial was made for categorical variables by using percent-pair agreement and the statistic and for continuous variables by using the mean difference ( question naire value minus clinical trial value ) and limits of agreement ( the range within which 95 % of the differences would be expected to occur , calculated as the mean difference 1.96 times the SD of the differences [ 17 ] ) . Results During the study period , 320 000 letters were mailed ; 5.3 % of these were returned because of an invalid address or death . Of the remaining letters , 30 % ( 91 000 letters ) were returned by persons willing to be screened . A total of 73 943 persons who were 50 to 79 years of age and did not have a history of AAA were screened ; 492 were excluded because the aorta could not be visualized . The remaining 73 451 patients constitute the study group , of whom 3.5 % were walk-ins . As Table 1 shows , the study group consisted primarily of men who had a history of smoking ( 97.2 % were male ; 75.5 % had a history of smoking ) . This closely reflects the population of U.S. veterans ( 96 % are male ; 74 % have a history of smoking [ 18 ] ) ; however , the study group also included 2078 women and 17 981 persons who had never smoked . Table 1 . Characteristics of 73 451 U.S. Veterans 50 to 79 Years of Age Screened for Abdominal Aortic Aneurysm * Abdominal aortic aneurysm , defined as an infrarenal aortic diameter of 3.0 cm or more , was detected in 3366 patients ( 4.6 % ) ; the infrarenal aortic diameter was at least 4.0 cm in 1031 patients ( 1.4 % ) . The frequencies of larger AAAs were as follows : Three hundred sixty-eight ( 0.50 % ) patients had an AAA of 5.0 cm or larger , 224 ( 0.30 % ) patients had an AAA of 5.5 cm or larger , 137 ( 0.19 % ) patients had an AAA of 6.0 cm or larger , 48 ( 0.07 % ) patients had an AAA of 7.0 cm or larger , and 22 ( 0.03 % ) patients had an AAA of 8.0 cm or larger . It can OBJECTIVES To test the acceptability of screening and to identify modifiable risk factors for abdominal aortic aneurysm ( AAA ) in men . DESIGN A trial of ultrasound screening for AAA in a population -based r and om sample of men aged 65 - 83 years , and a cross-sectional case-control comparison of men in the same sample . PARTICIPANTS 12,203 men who had an ultrasound examination of their abdominal aorta , and completed a question naire covering demographic , behavioural and medical factors . MAIN OUTCOME MEASURES Prevalence of AAA , and independent associations of AAA with demographic , medical and lifestyle factors . RESULTS Invitations to screening produced a corrected response of 70.5 % . The prevalence of AAAs ( > 30 mm ) rose from 4.8 % in men aged 65 - 69 years to 10.8 % in those aged 80 - 83 years . The overall prevalence of large ( > 50 mm ) aneurysms was 0.69 % . In a multivariate logistic model Mediterranean-born men had a 40 % lower risk of AAA ( > 30 mm ) compared with men born in Australia ( odds ratio [ OR ] , 0.6 ; 95 % CI , 0.4 - 0.8 ) , while ex-smokers had a significantly increased risk of AAA ( OR , 2.3 ; 95 % CI , 1.9 - 2.8 ) , and current smokers had even higher risks . AAA was significantly associated with established coronary and peripheral arterial disease and a waist : hip ratio greater than 0.9 ; men who regularly undertook vigorous exercise had a lower risk ( OR , 0.8 ; 95 % CI , 0.7 - 1.0 ) . CONCLUSION Ultrasound screening for AAA is acceptable to men in the likely target population . AAA shares some but not all of the risk factors for occlusive vascular disease , but the scope for primary prevention of AAA in later life is limited Background : To present actual data to estimate prevalence , incidence and mortality of known type 2 diabetes mellitus in all age categories in The Netherl and s. Methods : Prospect i ve population -based study between 1998 and 2000 in The Netherl and s. Baseline population of 155,774 patients , registered with 61 general practitioners participating in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC)- study . Results : Age- and sex-adjusted prevalence of type 2 diabetes was 2.2 % at baseline and 2.9 % after 2 years of follow-up ; for women and men it was 3.1 and 2.7 % at follow-up , respectively . Patients aged > 70 years account for almost 50 % of all type 2 diabetes patients . Age- and sex-adjusted mean annual incidence per 10,000 over 3 years was 22.7 overall ; for women 23.1 and for men 22.2 . Incidence - even though high - decreases after the age of 70 years . The mortality rate was 47.9/1000 and st and ardised mortality ratio 1.40 . Based on these results , the estimated total number of subjects known with type 2 diabetes was 466,000 for The Netherl and s in 2000 ; the number of patients with newly diagnosed diabetes 36,000 . Conclusions : Prevalence and incidence rates exceed all estimates regarding known type 2 diabetes for The Netherl and s. Elderly patients , aged 70 years and over , account for 50 % of the type 2 diabetic population . These results are important for health-care planning OBJECTIVE Abdominal aortic aneurysms ( AAAs ) share common risk factors with atherosclerosis , except for diabetes which appears protective . The reason for this is unknown . Although increased circulating concentrations of advanced glycation endproducts ( AGEs ) such as carboxymethyllysine ( CML ) are associated with occlusive vascular disease , it is possible that their effects on the aortic wall explain the paradoxically low incidence of AAAs in diabetes . METHODS We studied 234 community-dwelling men aged 65 to 79 years . The cases comprised all identifiable diabetic men with AAA ( aortic diameter > or = 30 mm on ultrasound ; n = 27 ) and r and omly-selected non-diabetic men with AAA ( n = 67 ) . Controls were age-matched r and omly-selected diabetic men ( n = 69 ) and age-matched r and omly-selected non-diabetic men ( n = 71 ) without AAA ( aortic diameter 18 to 22 mm ) . Serum CML concentrations were measured by vali date d indirect enzyme-linked immunosorbent assay ( ELISA ) . RESULTS Serum CML concentrations were significantly lower in men with AAAs than those without ( 6627 + /- 1544 vs 7309 + /- 1490 nmol/mol lysine ; P = .001 ) . Variables positively associated with AAA were height , diastolic blood pressure , smoking , a history of coronary heart disease , and serum creatinine ( P < or = .040 ) , while serum CML ( odds ratio [ 95 % confidence interval ] per 1000 nmol/mol lysine ; 0.80 [ 0.64 - 0.98 ] ) and a history of diabetes were inversely associated ( P < or = .040 ) . After adjusting , the interaction between diabetes status and serum CML was negatively associated with AAA ( P = .016 ) . CONCLUSION These cross-sectional data show that circulating concentrations of CML are reduced in diabetic men with AAAs . This is in contrast to studies of the relationship between AGEs and occlusive manifestations of cardiovascular disease and could explain the inverse association between diabetes and AAA BACKGROUND We previously reported the prevalence and associations of abdominal aortic aneurysm ( AAA ) in 73451 veterans aged 50 to 79 years who underwent ultrasound screening . OBJECTIVE To underst and the prevalence of and principal positive and negative risk factors for AAA , and to assess reproducibility of our previous findings . METHODS In the new cohort of veterans undergoing screening , 52 745 subjects aged 50 to 79 without history of AAA underwent successful ultrasound screening for AAA , after completing a question naire on demographics and potential risk factors . RESULTS We detected AAA of 4.0 cm or larger in 613 participants ( 1.2 % ; compared with 1.4 % in the earlier cohort ) . The direction and magnitude of the important associations reported in the first cohort were confirmed . Respective odds ratios for the major associations with AAA for the second and for the combined cohorts were as follows : 1.81 and 1.71 for age ( per 7 years ) , 0.12 and 0 . 18 for female sex , 0.59 and 0.53 for black race , 1.94 and 1.94 for family history of AAA , 4.45 and 5.07 for smoking , 0.50 and 0.52 for diabetes , and 1.60 and 1.66 for atherosclerotic diseases . The excess prevalence associated with smoking accounted for 75 % of all AAAs of 4.0 cm or larger in the total population of 126 196 . Associations for AAA of 3.0 to 3.9 cm were similar but tended to be somewhat weaker . CONCLUSIONS Our findings confirm our previous cohort findings . Age , smoking , family history of AAA , and atherosclerotic diseases remained the principal positive associations with AAA , and female sex , diabetes , and black race remained the principal negative associations OBJECTIVE to compare patients with abdominal aortic aneurysm ( AAA ) and aortic occlusive disease ( AOD ) with regard to risk factors for atherosclerosis , co-morbid conditions and inflammatory activity . PATIENTS AND METHODS a total of 155 patients undergoing abdominal aortic surgery between January 1993 and October 1997 : 82 ( 53 % ) had aneurysmal disease and 73 ( 47 % ) had occlusive disease . Principal risk factors were compared : age ; gender ; smoking ; hypertension ; hyperlipidaemia ; diabetes mellitus ; severe peripheral vascular disease ( PVD ) and ischaemic heart disease . Aortic wall tissue sample s were obtained during surgery . A prospect i ve blind analysis was performed for the presence of inflammatory cytokines TNF-alpha , IL-1 beta , IL-6 and TGF-beta . RESULTS the average age of AAA patients was 74 years ( 50 - 88 ) , while that of AOD patients was 61 years ( 43 - 82 ) ( p<0.0001 ) . Diabetes mellitus was found to be much more prevalent in the AOD group ( p<0.001 ) , while hypertension and severe PVD were more prevalent in the AAA group ( p<0.001 ) . No differences were found concerning any of the risk factors . Inflammatory cytokine activity : AAA tissue sample s contained significantly higher mean TNF-alpha and IL-6 levels compared to the AOD sample s ( 5.6+/-2.7 x 10 E-4 vs. 4.4+/-2.7 x 10 E-5 atmoles/microl ( p=0 . 01 ) , and 0.6+/-0.4 vs. 0.01+/-0.006 atmoles/microl ( p=0.02 ) respectively ) . No differences were found related to IL-1 beta and TGF-beta . CONCLUSIONS ( 1 ) Patients with AAA have fewer atherosclerotic risk factors than do patients with AOD . ( 2 ) Patients with AAA and AOD have significantly different inflammatory activity . ( 3 ) The data supports the hypothesis that AAA and AOD are probably two different pathological entities |
732 | 27,154,175 | After pooling all the eligible studies , we identified significant associations of GSTP1 Ile105Val polymorphism with chemotherapy-related tumor response ( G vs. A : OR 1.697 , 95 % CI 1.191–2.418 ; GG vs. AA : OR 2.804 , 95 % CI 1.414–5.560 ; AG vs. AA : OR 1.540 , 95 % CI 1.011–2.347 ; GG vs. AAAG : OR 2.139 , 95 % CI 1.256–3.641 ) , PFS ( GG vs. AA , HR 0.640 , 95 % CI 0.455–0.900 ; AGGG vs. AA : HR 0.718 , 95 % CI 0.562–0.919 ) , and OS ( AG vs. AA : HR 0.857 , 95 % CI 0.746–0.986 ; GG vs. AA : HR 0.679 , 95 % CI 0.523–0.882 ; AGGG vs. AA : HR 0.663 , 95 % CI 0.542–0.812 ) in gastric and colorectal cancers and no significant association was found between the polymorphism with toxicity .
Conclusions GSTP1 Ile105Val polymorphism was associated with tumor response , PFS , and OS in gastric and colorectal cancers after chemotherapy | Purpose Gastric and colorectal cancers remain the major causes of cancer-related death with a bad prognosis .
Up to now , platinum combined with fluoropyrimidines has been most commonly used in chemotherapy regimens of gastric and colorectal cancers .
Recently , a series of studies have been conducted to investigate the associations of biomarkers , such as GSTP1 Ile105Val polymorphism , with the chemotherapy efficacy in gastric and colorectal cancers ; however , the results were not consistent and inconclusive .
Here , we performed a systematic review and meta- analysis to summarize the associations of GSTP1 Ile105Val polymorphism with the chemotherapy efficacy in gastric and colorectal cancers . | Purpose : Oxaliplatin displays a frequent dose-limiting neurotoxicity due to its interference with neuron voltage-gated sodium channels through one of its metabolites , oxalate , a calcium chelator . Different clinical approaches failed in neurotoxicity prevention , except calcium-magnesium infusions . We characterized oxalate outcome following oxaliplatin administration and its interference with cations and amino acids . We then looked for genetic predictive factors of oxaliplatin-induced neurotoxicity . Experimental Design : We first tested patients for cations and oxalate levels and did amino acid chromatograms in urine following oxaliplatin infusion . In the second stage , before treatment with FOLFOX regimen , we prospect ively looked for variants in genes coding for the enzymes involved ( a ) in the oxalate metabolism , especially glyoxylate aminotransferase ( AGXT ) , and ( b ) in the detoxification glutathione cycle , glutathione S-transferase π , and for genes coding for membrane efflux proteins ( ABCC2 ) . Results : In the first 10 patients , urinary excretions of oxalate and cations increased significantly within hours following oxaliplatin infusion , accompanied by increased excretions of four amino acids ( glycine , alanine , serine , and taurine ) linked to oxalate metabolism . In a further 135 patients , a minor haplotype of AGXT was found significantly predictive of both acute and chronic neurotoxicity . Neither glutathione S-transferase π nor ABCC2 single nucleotide polymorphisms we looked for were linked to neurotoxicity . Conclusion : These data confirm the involvement of oxalate in oxaliplatin neurotoxicity and support the future use of AGXT genotyping as a pretherapeutic screening test to predict individual susceptibility to neurotoxicity Background The objective of this study was to evaluate the efficacy and toxicity of infusional 5-fluorouracil ( 5-FU ) , folinic acid and oxaliplatin ( modified FOLFOX-6 ) in patients with advanced gastric cancer ( AGC ) , as first-line palliative combination chemotherapy . We also analyzed the predictive or prognostic value of germline polymorphisms of c and i date genes associated with 5-FU and oxaliplatin . Methods Seventy-three patients were administered a 2 hour infusion of oxaliplatin ( 100 mg/m2 ) and folinic acid ( 100 mg/m2 ) followed by a 46 hour continuous infusion of 5-FU ( 2,400 mg/m2 ) . Genomic DNA from the patients ' peripheral blood mononuclear cells was extracted . Ten polymorphisms within five genes were investigated including TS , GSTP , ERCC , XPD and XRCC . Results The overall response rate ( RR ) was 43.8 % . Median time to progression ( TTP ) and overall survival ( OS ) were 6.0 months and 12.6 months , respectively . Toxicities were generally tolerable and manageable . The RR was significantly higher in patients with a 6-bp deletion homozygote ( -6 bp/-6 bp ) in TS-3'UTR ( 55.0 % vs. 30.3 % in + 6 bp/+6 bp or + 6 bp/-6 bp , p = 0.034 ) , and C/A or A/A in XPD156 ( 52.0 % vs. 26.1 % in C/C , p = 0.038 ) . The -6 bp/-6 bp in TS-3'UTR was significantly associated with a prolonged TTP and OS . In a multivariate analysis , the 6-bp deletion in TS-3'UTR was identified as an independent prognostic marker of TTP ( hazard ratio = 0.561 , p = 0.032 ) . Conclusion Modified FOLFOX-6 chemotherapy appears to be active and well tolerated as first line chemotherapy in AGC patients . The 6-bp deletion in TS-3'UTR might be a c and i date to select patients who are likely to benefit from 5-FU based modified FOLFOX-6 in future large scale trial A Valine residue at position 105 of the GSTP1 protein results in decreased enzyme activity . As nuclear GSTP1 activity decreases irinotecan cytotoxicity , Val-allele carriers may benefit more from irinotecan chemotherapy . Our aim was to investigate the association of GSTP1 genotype with treatment outcome of irinotecan . Progression-free survival ( PFS ) and toxicity were determined in 267 metastatic colorectal cancer ( MCRC ) patients who were treated with first-line capecitabine ( CAP ) plus irinotecan ( CAPIRI ) , or CAP single agent in a prospect i ve r and omised phase III trial ( CAIRO ) . GSTP1 genotype was determined by Pyrosequencing . Patients receiving CAP showed a PFS of 6.6 ( Ile/Ile ) , 6.0 ( Ile/Val ) and 6.5 months ( Val/Val ) ; compared to 7.0 ( Ile/Ile ) , 8.8 ( Ile/Val ) and 9.2 months ( Val/Val ) with CAPIRI . Median PFS was 2.7 months longer in Val-allele carriers treated with CAPIRI compared to CAP ( P=0.005 ) . Patients with the Ile/Ile genotype showed similar PFS with CAPIRI and CAP ( 7.0 compared to 6.6 months , P=0.972 ) . Toxicity did not differ significantly among genotypes . GSTP1 codon 105 polymorphism may be predictive for the response to irinotecan-based chemotherapy in patients with MCRC , with the Val-allele being associated with a better outcome . Ile/Ile genotype patients do not appear to benefit from the addition of irinotecan to CAP Objective In Japan , there had been no prospect i ve clinical studies conducted in terms of modified FOLFOX6 + bevacizumab therapy . We performed a post-marketing Phase II multicenter clinical study to examine the efficacy and safety of this regimen as first-line therapy for Japanese patients with advanced/recurrent colorectal cancer . Methods Bevacizumab ( 5 mg/kg ) was administered intravenously , and then oxaliplatin ( 85 mg/m2 ) and levofolinate calcium ( 200 mg/m2 ) were infused intravenously over 2 h. Subsequently , a bolus dose of 5-fluorouracil ( 400 mg/m2 ) was injected , followed by infusion of 5-fluorouracil ( 2400 mg/m2 ) for 46 h. This regimen was repeated every 2 weeks until 24 cycles unless there was disease progression , unacceptable toxicity or patient refusal . The primary end point was the response rate . Results Among the 70 patients enrolled , two patients withdrew the study before treatment , and 68 patients were eligible for analysis of efficacy and safety . The response rate was 51.5 % ( 95 % confidence interval : 39.0–63.8 % ) . The median progression-free survival and median overall survival time were 12.6 months ( 95 % confidence interval : 10.4–14.5 months ) and 28.5 months [ 95 % confidence interval : 23.1 months–(not applicable ) ] , respectively . There were no treatment-related deaths observed . The most common Grade 3 and 4 adverse events included neutropenia in 35.3 % of the patients , peripheral neuropathy in 16.2 % and hypertension in 16.2 % . All adverse events were manageable and tolerable . The exploratory analysis of polymorphisms of three genes , ERCC1 , XPD and GSTP1 , did not show any trends in terms of correlation with the efficacy or safety of modified FOLFOX6 + bevacizumab therapy . Conclusions Modified FOLFOX6 + bevacizumab therapy was manageable and tolerable in Japanese patients , achieving a high response rate We investigated 17 polymorphisms in 11 genes ( TS , MTHFR , ERCC1 , XRCC1 , XRCC3 , XPD , GSTT1 , GSTP1 , GSTM1 , ABCC1 , ABCC2 ) for their association with the toxicity of fluoropyrimidines and oxaliplatin in colorectal cancer patients enrolled in a prospect i ve r and omized trial of adjuvant chemotherapy . The TOSCA Italian adjuvant trial was conducted in high-risk stage II – III colorectal cancer patients treated with 6 or 3 months of either FOLFOX-4 or XELOX adjuvant chemotherapy . In the concomitant ancillary pharmacogenetic study , the primary endpoint was the association of polymorphisms with grade 3–4 CTCAE toxicity events ( grade 2–4 for neurotoxicity ) . In 517 analyzed patients , grade ≥ 3 neutropenia and grade ≥ 2 neurotoxicity events occurred in 150 ( 29 % ) and in 132 patients ( 24.8 % ) , respectively . Diarrhea grade ≥ 3 events occurred in 34 ( 6.5 % ) patients . None of the studied polymorphisms showed clinical ly relevant association with toxicity . Hopefully , genome-wide association studies will identify new and more promising genetic variants to be tested in future studies Objectives We aim ed to evaluate the efficacy and safety of combination therapy of Endostar ( recombinant human endostatin ) and S-1 combined with oxaliplatin ( SOX ) in patients with advanced gastric cancer . Methods In this r and omized , controlled trial , 165 late-stage gastric cancer patients were assigned to the experimental arm with Endostar in combination with SOX ( 80 patients ) and the control arm with SOX alone ( 85 patients ) . The end points of this study included progression-free survival , response rate , and disease-control rate . Results There was no statistically significant difference in response rate between the experimental arm and the control arm ( 53.8 % vs 42.4 % , P=0.188 ) . The difference in disease-control rate was also statistically insignificant between the two arms ( 85.0 % vs 72.9 % , P=0.188 ) . Progression-free survival in the experimental arm was significantly higher than that in the control arm ( 15.0 months vs 12.0 months , P=0.0001 ) . Common adverse events included immunosuppression , gastrointestinal distress , and neuropathy . There was no statistical difference in the incidences of adverse events . Conclusion Combination therapy of Endostar and SOX provides therapeutic benefits to advanced gastric cancer patients , with tolerable adverse effects Oxaliplatin and irinotecan have proven effective in the treatment of gastric cancer . We attempted to determine whether single nucleotide polymorphisms in ERCC1 , GST , TS and UGT1A1 predicted overall survival in gastric cancer patients receiving FOLFOX and /or FOLFIRI chemotherapy . Total genomic DNA was extracted from the whole blood of patients . The PCR-restriction fragment length polymorphism technique was applied in order to detect the known variant sites of ERCC1 , GST , TS and UGT1A1 . The response rate of FOLFOX ( N=75 ) was 24 % . Grade 3 - 4 neutropenia and neurotoxicity were observed at frequencies of 34.7 and 16 % , respectively . TTP and OS of first-line administration of FOLFOX ( N=35 ) were 3.1 months ( 95 % CI , 0.1 - 6.1 months ) and 13.9 months ( 95 % CI , 12.2 - 15.6 months ) , respectively . Only the GSTM1 positive genotype exhibited a significantly better time to progression ( P=0.023 ) . However , significant genotypic variation of TS , GST and ERCC1 , which was assumed to affect the activity of oxaliplatin , was not observed to affect RR , toxicity and overall survival . The response rate of FOLFIRI ( N=74 ) was 23 % . Grade 3 - 4 neutropenia and diarrhea were observed in 55.4 and 9.5 % of cases , respectively . TTP and OS of first-line administration of FOLFIRI ( N=33 ) was 4.9 months ( 95 % CI , 3.5 - 6.4 months ) and 19.0 months ( 95 % CI , 8.5 - 29.5 months ) . The low expression type ( 2R/2R , 2R/3C and 3C/3C ) of TS was associated with a high incidence of grade > or=3 neutropenia . However , significant genotypic variation of UGT1A1 , which was assumed to affect irinotecan toxicity , was not observed to affect RR , toxicity or survival . In this study , the GSTM1 positive genotype evidence d a significantly better time to progression in cases of advanced gastric cancer being treated with FOLFOX . The low expression type ( 2R/2R , 2R/3C and 3C/3C ) of TS was associated with a high incidence of grade > or=3 neutropenia in cases of advanced gastric cancer treated with FOLFIRI The discovery of pharmacogenomic markers in colorectal cancer ( CRC ) could be setting -specific . FOLFOX4 is employed in the adjuvant and metastatic setting in CRC . This prospect i ve study is aim ed to vali date in the adjuvant setting the pharmacogenomic markers of toxicity reported in the metastatic setting ( that is , GSTP1-rs947894 , and -rs1138272 ; GSTM1-null genotype ; AGXT-rs4426527 , -rs34116584 and del-74 bp ) , and to discover additional markers . CRC patients ( n=144 ) treated with adjuvant FOLFOX4 were genotyped for 57 polymorphisms in 29 genes . Grade ⩾2 neurotoxicity was associated ( false discovery rate-adjusted q-value < 0.1 ) with single-nucleotide polymorphisms in ABCC1 ( rs2074087 : odds ratio=0.43(0.22–0.86 ) ) , and ABCC2 ( rs3740066 : 2.99(1.16–7.70 ) ; rs1885301 : 3.06(1.35–6.92 ) ; rs4148396 : 4.69(1.60–13.74 ) ; rs717620 : 14.39(1.63–127.02 ) ) . hMSH6-rs3136228 was associated with grade 3–4 neutropenia ( 3.23(1.38–7.57 ) , q-value=0.0937 ) . XRCC3-rs1799794 was associated with grade 3–4 non-hematological toxicity ( 8.90(2.48–31.97 ) , q-value=0.0150 ) . The markers previously identified in metastatic CRC were not vali date d. We have identified new markers of toxicity in genes of transport and DNA repair . If vali date d in other studies , they could help to identify patients at risk of toxicity Purpose The aim of this study was to assess whether genetic polymorphisms in p53 , glutathione S-transferase P1 ( GSTP1 ) , GSTM1 , excision repair cross complementing group 1 ( ERCC1 ) and X-ray repair cross-complementing group 1 ( XRCC1 ) genes are associated with clinical outcome of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy . Methods The genetic polymorphisms in p53 , GSTP1,GSTM1 ( null ) , ERCC1 and XRCC1 were determined in 102 gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy using polymerase chain reaction-ligation detection reaction method . Results Among the five studied polymorphisms , p53 codon 72 Pro/Pro , GSTP1 codon 105 Ile/Ile , and XRCC1 codon 399 Gln/Gln + Arg/Gln were associated with poor relapse-free survival and overall survival ( P < 0.05 ) ; and the prognostic effect was retained in the Cox multivariate analysis . Combination analysis with the three polymorphisms using the Kaplan – Meier method and Cox multivariate analysis revealed that the relapse-free and overall survivals significantly increase with the number of favorable genotypes ( P < 0.05 ) . No significant association was found between the GSTM1 ( null ) or the ERCC1 codon 118 genotypes and the clinical outcome ( P > 0.05 ) . Conclusion Testing for p53 Arg72Pro , GSTP1 Ile105Val , and XRCC1 Arg399Gln polymorphisms may allow identification of gastric cancer patients who will benefit from oxaliplatin-based adjuvant chemotherapy . Selecting specific adjuvant treatments according to the individual genetic background may represent an innovative strategy that warrants prospect i ve studies Background : Our study aim ed to investigate the relationship between glutathione S-transferase P1 ( GSTP1 ) , 5,10-methylenetetrahydrofolate reductase ( 5,10-MTHFR ) and X-ray repair cross complementing group 1 ( XRCC1 ) gene polymorphisms and the response to chemotherapy in advanced gastric cancer . Patients and Methods : 59 cases of advanced gastric cancer were enrolled . All patients were treated with the DCF regimen comprising docetaxel , cisplatin , and 5-fluorouracil . All patients ' genotypes regarding GSTP1 , XRCC1 , and 5,10-MTHFR were analyzed by polymerase chain reaction/ligase detection reaction ( PCR-LDR ) . Results : There were 15 ( 25.42 % ) cases of G/G genotype , 21 ( 35.59 % ) of G/A genotype , and 23 ( 38.98 % ) of A/A genotype for GSTP1 , 16 ( 27.12 % ) cases of A/A genotype , 18 ( 30.51 % ) of G/A genotype , and 25 ( 42.37 % ) of G/G genotype for XRCC1 , and 21 ( 35.59 % ) cases of C/C genotype , 22 ( 37.29 % ) of C/T genotype , and 16 ( 27.12 % ) of T/T genotype for 5,10-MTHFR . After 2 cycles of chemotherapy , there were 4 cases of complete remission , 14 of partial remission , 19 of stable disease , and 22 of advanced disease , with a total effective rate of 30.51 % . Better survival was shown for GSTP1 G/G genotype , XRCC1 A/A genotype , and 5,10-MTHFR T/T genotype ( p < 0.05 ) . Conclusion : The gene polymorphisms of GSTP1 G/G , XRCC1 A/A , and 5,10-MTHFR T/T have clinical value for predicting the response to the DCF regimen for advanced gastric cancer PURPOSE Oxaliplatin is detoxified by conjugation to glutathione via the enzyme Glutathione-S-transferase pi ( GSTP1 ) . The aim of this study is to investigate the association of GSTP1 Ile105Val genetic polymorphism with oxaliplatin efficacy and toxicity in advanced colorectal cancer ( ACC ) patients . EXPERIMENTAL DESIGN A total of 91 ACC patients received capecitabine and oxaliplatin ( CAPOX ) as a part of a multicentre phase-III study of the Dutch Colorectal Cancer Group . Tumour response was evaluated according to RECIST , toxicity was grade d using CTC , and GSTP1 Ile105Val was determined by pyrosequencing . RESULTS Overall survival after CAPOX was similar for patients with the Ile/Ile ( 11.5 mo ) , Ile/Val ( 11.6 mo ) and Val/Val ( 12.6 mo ) genotypes ( p=0.602 ) . Likewise , there were no statistically significant differences in progression-free survival ( p=0.252 ) . Overall grade s 3 - 4 toxicity was not related to genotype ( p=0.313 ) . There were no differences in any grade or grade s 3 - 4 neurotoxicity amongst the patients who received > or = 500 mg/m(2 ) of oxaliplatin ( p-values of 0.376 and 0.772 , respectively ) . CONCLUSIONS The results of this study indicate that the GSTP1 genotype is not predictive for progression-free survival or overall survival in ACC patients treated with CAPOX . Moreover , overall neurotoxicity and neurotoxicity in patients receiving 500 mg/m(2 ) of oxaliplatin was not associated with GSTP1 genotype PURPOSE Predicting efficacy and toxicity could potentially allow individualization of cancer therapy . We investigated putative pharmacogenetic markers of chemotherapy toxicity in a large r and omized trial . PATIENTS , MATERIAL S , AND METHODS Patients were r and omly assigned to different sequences of chemotherapy for advanced colorectal cancer . First-line therapy was fluorouracil ( FU ) , irinotecan/FU ( IrFU ) or oxaliplatin/FU ( OxFU ) . Patients allocated first-line FU had planned second-line irinotecan alone , IrFU , or OxFU . The primary toxicity outcome measure was toxicity-induced delay or dose reduction ; the secondary outcome was Common Terminology Criteria of Adverse Events grade > or= 3 toxicity . DNA was analyzed in 1,188 patients ; 1,036 were assessable for the primary outcome , including 688 treated with FU , 270 with IrFU ( first or second line ) , 280 with OxFU ( first or second line ) , 184 with irinotecan alone , and 454 with any irinotecan-containing regimen . Ten polymorphisms were assessed : thymidylate synthase-enhancer region ( TYMS-ER ) , thymidylate synthase 1494 ( TYMS-1494 ) , dihydropyrimidine dehydrogenase ( DPYD ) , methylenetetrahydrofolate reductase ( MTHFR ) , mutL homolog 1 ( MLH1 ) , UDP glucuronyltransferase ( UGT1A1 ) , ATP-binding cassette group B gene 1 ( ABCB1 ) , x-ray cross-complementing group 1 ( XRCC1 ) , glutathione-S-transferase P1 ( GSTP1 ) , and excision repair cross-complementing gene 2 ( ERCC2 ) . Results Using the primary outcome measure , no polymorphism was significantly associated ( P < .01 ) with the toxicity of any regimen or with the difference in toxicity of IrFU or OxFU versus FU alone . Trends ( of doubtful significance ) were seen for associations of XRCC1 , ERCC2 , and GSTP1 with toxicity during irinotecan regimens : XRCC1 , primary end point , any irinotecan-containing regimen ( P = .045 ) ; ERCC2 , secondary end point , irinotecan alone ( P = .003 ) ; GSTP1 , secondary end point ; IrFU ( P = .039 ) ; and irinotecan alone ( P = .05 ) . There was no evidence of association of UGT1A1 * 28 with irinotecan toxicity . CONCLUSION These results do not support the routine clinical use of the evaluated polymorphisms , including UGT1A1 * 28 . Further investigation of XRCC1 , ERCC2 , and GSTP1 as potential predictors of irinotecan toxicity is warranted WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Numerous clinical studies , including a few prospect i ve ones , have reported conflicting results on the impact of gene polymorphisms related to fluorouracil ( FU ) and oxaliplatin pharmacodynamics . WHAT THIS STUDY ADDS * This prospect i ve study is the first to report that clinical response to FOLFOX is significantly related to methylenetetrahydrofolate reductase ( MTHFR ) gene polymorphisms ( 677C-->T and 1298A-->C ) , with a response rate of 37 , 53 , 63 and 80 % in patients harbouring no , one , two or three favourable MTHFR alleles , respectively . * Only polymorphisms of genes related to oxaliplatin pharmacodynamics ( GSTpi 105Ile-->Val and XPD 751Ly-->Gln ) influenced progression-free survival . * These results corroborate the observation that response was related to the cumulative FU dose , whereas progression-free survival was related to the cumulative oxaliplatin dose . AIMS To test prospect ively the predictive value of germinal gene polymorphisms related to fluorouracil ( FU ) and oxaliplatin ( Oxa ) pharmacodynamics on toxicity and responsiveness of colorectal cancer ( CRC ) patients receiving FOLFOX therapy . METHODS Advanced CRC patients ( n= 117 ) receiving FOLFOX 7 therapy were enrolled . Gene polymorphisms relevant for FU [ thymidylate synthase ( TYMS , 28 bp repeats including the G-->C mutation + 6 bp deletion in 3'UTR ) , methylenetetrahydrofolate reductase ( MTHFR , 677C-->T , 1298A-->C ) , dihydropyrimidine deshydrogenase ( IVS14 + 1G-->A ) and Oxa : glutathione S-transferase ( GST ) pi ( 105Ile-->Val , 114Ala-->Val ) , excision repair cross-complementing group 1 ( ERCC1 ) ( 118AAT-->AAC ) , ERCC2 ( XPD , 751Lys-->Gln ) and XRCC1 ( 399Arg-->Gln ) ] were determined ( blood mononuclear cells ) . RESULTS None of the genotypes was predictive of toxicity . Response rate ( 54.7 % complete response + partial response ) was related to FU pharmacogenetics , with both 677C-->T ( P= 0.042 ) and 1298A-->C ( P= 0.004 ) MTHFR genotypes linked to clinical response . Importantly , the score of favourable MTHFR alleles ( 677 T and 1298C ) was positively linked to response , with response rates of 37.1 , 53.3 , 62.5 and 80.0 % in patients bearing no , one , two or three favourable alleles , respectively ( P= 0.040 ) . Polymorphisms of genes related to Oxa pharmacodynamics showed an influence on progression-free survival , with a better outcome in patients bearing GSTpi 105 Val/Val genotype or XPD 751Lys-containing genotype ( P= 0.054 ) . CONCLUSIONS These results show that response to FOLFOX therapy in CRC patients may be driven by MTHFR germinal polymorphisms PURPOSE The objective is to investigate whether polymorphisms with putative influence on fluorouracil/oxaliplatin activity are associated with clinical outcomes of patients with advanced colorectal cancer treated with first-line oxaliplatin , folinic acid , and fluorouracil palliative chemotherapy . MATERIAL S AND METHODS Consecutive patients were prospect ively enrolled onto medical oncology units in Central Italy . Patients were required to have cytologically/histologically confirmed metastatic disease with at least one measurable lesion . Peripheral blood sample s were used for genotyping 12 polymorphisms in thymidylate synthase , methylenetetrahydrofolate reductase , xeroderma pigmentosum group D ( XPD ) , excision repair cross complementing group 1 ( ERCC1 ) , x-ray cross complementing group 1 , x-ray cross complementing protein 3 , glutathione S-transferases ( GSTs ) genes . The primary end point of the study was to investigate the association between genotypes and progression-free survival ( PFS ) . RESULTS In 166 patients , ERCC1 - 118 T/T , XPD-751 A/C , and XPD-751 C/C genotypes were independently associated with adverse PFS . The presence of two risk genotypes ( ERCC1 - 118 T/T combined with either XPD-751 A/C or XPD-751 C/C ) occurred in 50 patients ( 31 % ) . This profiling showed an independent role for unfavorable PFS with a hazard ratio of 2.84 % and 95 % CI of 1.47 to 5.45 ( P = .002 ) . Neurotoxicity was significantly associated with GSTP1 - 105 A/G. Carriers of the GSTP1 - 105 G/G genotype were more prone to suffer from grade 3 neurotoxicity than carriers of GSTP1 - 105 A/G and GSTP1 - 105 A/A genotypes . CONCLUSION A pharmacogenetic approach may be an innovative strategy for optimizing palliative chemotherapy in patients with advanced colorectal cancer . These findings deserve confirmation in additional prospect i ve studies PURPOSE To investigate whether polymorphisms with putative influence on fluorouracil/cisplatin activity are associated with clinical outcomes of patients with advanced gastric cancer ( AGC ) . PATIENTS AND METHODS Peripheral blood sample s from 175 prospect ively enrolled AGC patients treated with fluorouracil/cisplatin palliative chemotherapy were used for genotyping 13 polymorphisms in nine genes ( TS , MTHFR , XPD , ERCC1 , XRCC1 , XRCC3 , GSTPI , GSTTI , GSTMI ) . Genotypes were correlated to response and survival . RESULTS The overall response rate was 41 % , the median progression-free survival ( PFS ) was 24 weeks ( range , 4 to 50 weeks ) , and the median overall survival ( OS ) was 39 weeks ( range , 8 to 72 + weeks ) . Chemoresistance and poor survival were significantly associated with TS 5'-UTR 3G-genotype ( 2R/3 G , 3C/3 G , 3G/3 G ) and GSTP1 105 A/A homozygous genotype . Sixty-one patients ( 35 % ) did not show any of these risk genotypes ( group 0 ) , 57 patients ( 32.5 % ) showed one of the two risk genotypes ( group 1 ) , and 57 patients ( 32.5 % ) showed both risk genotypes ( group 2 ) . Median PFS and OS in group 0 patients were 32 weeks ( range , 8 to 50 weeks ) and 49 weeks ( range , 18 to 72 + weeks ) , respectively . Group 1 and group 2 patients showed significantly worse PFS ( median , 26 weeks [ range , 6 to 44 weeks ] and 14 weeks [ range , 4 to 38 weeks ] , respectively ) and worse OS ( median , 39 weeks [ range , 10 to 58 weeks ] and 28 weeks [ range , 8 to 56 weeks ] ) , respectively , than group 0 patients . This adverse effect was retained in multivariate analysis . CONCLUSION Specific polymorphisms may influence clinical outcomes of AGC patients . Selecting palliative chemotherapy on the basis of pretreatment genotyping may represent an innovative strategy that warrants prospect i ve studies |
733 | 23,407,298 | Comparisons between different simulation interventions ( n = 79 studies ) clarified best practice s. For example , in comparison with virtual reality , box trainers have similar effects for process skills outcomes and seem to be superior for outcomes of satisfaction and skills time .
CONCLUSIONS Simulation-based laparoscopic surgery training of health professionals has large benefits when compared with no intervention and is moderately more effective than nonsimulation instruction | OBJECTIVE Summarize the outcomes and best practice s of simulation training for laparoscopic surgery .
BACKGROUND Simulation-based training for laparoscopic surgery has become a mainstay of surgical training .
Much new evidence has accrued since previous review s were published . | OBJECTIVE " Dry lab " facilities are integral to laparoscopy training , but access is often limited due to the high costs of video-laparoscopy equipment . We assessed the effectiveness of a cheap and simple training model compared to conventional video-laparoscopy for basic training using a r and omised , blinded study . METHODS Thirty-six third-year medical students without previous surgical skills were r and omised into two groups : group A students were taught basic laparoscopy skills using a conventional video-laparoscopy pelvic trainer and group B students were taught similar techniques using a cardboard box with a cut-out top to allow light and visualisation . Participants in group B had one eye obscured to reduce their stereoscopic vision . After eight sessions of training amounting to 24h , the two groups were assessed by a blinded adjudicator on set tasks using both the video-laparoscopy pelvic trainer and the cardboard box . Accuracy , timing and depth perception were assessed and the results compared . RESULTS There was no significant difference in performance scores or times between the two groups in any of the parameters when tested on the cardboard box . However , when assessed on the video trainer , the cardboard box-trained group had significantly faster times with equivalent scores in the majority of tasks . CONCLUSION For basic laparoscopic training the cardboard box , costing nothing , is a simple and effective alternative , which can be used in conjunction with sophisticated video-laparoscopy equipment costing thous and s of dollars Background Laparoscopic suturing is one of the most difficult tasks in endoscopic surgery , requiring extensive training . The aim of this study was to determine the transfer validity of knot-tying training on a virtual-reality ( VR ) simulator to a realistic laparoscopic environment . Methods Twenty surgical trainees underwent basic eye – h and coordination training on a VR simulator ( SIMENDO , DelltaTech , Delft , the Netherl and s ) until predefined performance criteria were met . Then , they were r and omized into two groups . Group A ( the experimental group ) received additional training with the knot-tying module on the simulator , during which they had to tie a double laparoscopic knot ten times . Group B ( controls ) did not receive additional manual training . Within a week the participants tied a double knot in the abdominal cavity of an anaesthetized porcine model . Their performance was captured on digital video and coded . Objective analysis parameters were : time taken to tie the knot and number of predefined errors made . Subjective assessment s were also made by two laparoscopic surgeons using a global rating list with a five-point Likert scale . Results Trainees in group A ( n = 9 ) were significantly faster than the controls ( n = 10 ) , with a median of 262 versus 374 seconds ( p = 0.034 ) . Group A made a significantly lower number of errors than the controls ( median of 24 versus 36 errors , p = 0.030 ) . Subjective assessment s by the laparoscopic experts did not show any significant differences in economy of movement and erroneous behavior between the two groups . ConclusionS urgical trainees who received knot-tying training on the VR simulator were faster and made fewer errors than the controls . The VR module is a useful tool to train laparoscopic knot-tying . Opportunities arose to improve simulator-based instruction that might enhance future training Background : The study aim was to compare the effectiveness of virtual reality and computer-enhanced video-scopic training devices for training novice surgeons in complex laparoscopic skills . Methods : Third-year medical students received instruction on laparoscopic intracorporeal suturing and knot tying and then underwent a pretraining assessment of the task using a live porcine model . Students were then r and omized to objectives -based training on either the virtual reality ( n=8 ) or computer-enhanced ( n=8 ) training devices for 4 weeks , after which the assessment was repeated . Results : Posttraining performance had improved compared with pretraining performance in both task completion rate ( 94 % versus 18 % ; P<0.001 * ) and time [ 181±58 ( SD ) versus 292±24 * ] . Performance of the 2 groups was comparable before and after training . Of the subjects , 88 % thought that haptic cues were important in simulators . Both groups agreed that their respective training systems were effective teaching tools , but computer-enhanced device trainees were more likely to rate their training as representative of reality ( P<0.01 ) . Conclusions : Training on virtual reality and computer-enhanced devices had equivalent effects on skills improvement in novices . Despite the perception that haptic feedback is important in laparoscopic simulation training , its absence in the virtual reality device did not impede acquisition of skill Background Many laparoscopic simulation training systems exist and have been shown to transfer learning of surgical skills to the operating room . The manner in which the training is structured to maximize learning has not been examined . There are many aspects to the acquisition of laparoscopic skills during training , one of which is the availability of knowledge of results ( KR ) . Knowledge of results is information about the outcome of motor skill execution , usually provided to individuals at the end of the execution . The timing and nature of KR can affect how well people learn new motor skills . In addition , detailed instruction during learning can also affect skill acquisition . We studied the effects of KR and instruction on the learning curve of a suturing and knot-tying task . We hypothesized that KR was necessary for skill acquisition , and that detailed instruction would help trainees to learn to perform the task more correctly and reach a performance plateau earlier . In addition , the overall workload of a trainee during training would decrease as skills improved , especially when KR and coaching were provided . Methods Nine medical students with no previous laparoscopic surgical experience were r and omly and evenly divided into three groups with different KR conditions : ( 1 ) no KR , ( 2 ) KR , ( 3 ) KR + instruction . Each subject attended a training session for 1 h each day , 6 days a week for 4 consecutive weeks . Performance measures such as task time , smoothness of instrument , and path length were recorded for each trial . Workload was assessed using the NASA-TLX question naire . Results While KR was necessary for learning to suture , continual instruction had limited additional benefits . However , KR + instruction did reduce subjects ’ perceived overall workload . Conclusions Surgical training could be carried out effectively with only knowledge of results . These results have implication s for the staffing of surgical skills laboratories Background Training of skills in simulators is preferred over learning on patients so as to avoid undue injury to patients and to allow more efficient use of re sources . Most simulators are costly and require a dedicated space . The aim of this study was to evaluate a simple desktop simulator , the Mirror Trainer . Methods Thirty medical students were r and omly assigned to three groups . One group was taught laparoscopic suturing in the Mirror Trainer , the second group used a pelvic training box , while the third group served as a control group and did not receive any training . All suture attempts during training were recorded on video . A blinded , independent investigator analyzed the videos . At the completion of training , the suturing skills of each participant were evaluated in an animal model . Results Training with the Mirror Trainer required less time than with the pelvic trainer ( p < 0.001 ) . Compared with the control group , the Mirror Trainer group and the pelvic trainer group were significantly faster at creating three knots in the pig ( p = 0.001 and p = 0.004 , respectively ) . Both training groups performed equally well on the animal model ( p = 0.99 ) . Conclusion The Mirror Trainer and the pelvic trainer are equally effective in teaching laparoscopic suturing skills but training with the Mirror Trainer requires less time , can be done on any desktop , and is less costly BACKGROUND We carried out a prospect i ve , r and omized , 4-arm study including control arm , blinding of examiners to determine effectiveness of computer-based video instruction ( CBVI ) and different types of expert feedback ( concurrent and summary ) on learning of a basic technical skill . METHODS Using bench models , participants were pre-tested on a suturing and instrument knot-tying skill after viewing an instructional video . The students were subsequently assigned r and omly to 4 practice conditions : no additional intervention ( control ) , self study with CBVI , expert feedback during practice trials ( concurrent feedback ) , and expert feedback after practice trials ( summary feedback ) . All participants underwent 19 trials of practice , over 1 hour , in their assigned training condition . The effectiveness of training was assessed both at an immediate post-test and 1 month later at a retention test . Performance was evaluated using both expert-based ( Global Rating Scores ) and computer-based assessment ( H and Motion Analysis ) . Data were analyzed using repeated- measures ANOVA . RESULTS There were no differences in GRS between groups at pre-test . The CBVI , concurrent feedback and summary feedback methods were equally effective initially for the instruction of this basic technical skill to naive medical students and displayed better performance than control ( control , 12.71 [ 10.79 to 14.62 ] ; CBVI , 16.39 [ 14.38 to 18.40 ] ; concurrent , 16.97 [ 15.79 to 18.15 ] ; summary , 16.09 [ 13.57 to 18.62 ] ; P < .001 each ) . At retention . however , only CBVI and summary feedback groups retained superior suturing and knot-tying performance versus control ( control , 8.13 [ 6.94 to 9.85 ] ; CBVI , 11.92 [ 10.19 to 14.99 ] P = .037 ; concurrent , 9.80 [ 8.55 to 13.45 ] P = .635 ; summary , 111.19 [ 10.27 to 14.29 ] P = .037 ) . H and motion data displayed a similar pattern of results . There were no group differences in the rate of learning ( P > .05 ) . CONCLUSION Our study showed that CBVI can be as effective as summary expert feedback in the instruction of basic technical skills to medical students . Thoughtfully incorporated into technical curricula , CBVI can make efficient use of faculty time and serve as a useful pedagogic adjunct for basic skills training . Additionally , our study provides evidence supporting an increased role of summary feedback to effectively train novices in technical skills BACKGROUND Based on prior success of virtual-reality ( VR ) trainers in imparting surgical skills , a r and omized and controlled study was design ed to determine whether VR training improves angled-telescope operative performance . METHODS Third-year medical students received instruction on the use of an angled laparoscope and subsequently underwent performance assessment of angled telescope navigational tasks in an anesthetized porcine model . Subjects were then r and omized to objective -based training with an angled-telescope simulator ( EndoTower ; Verefi Technologies , Elizabethtown , PA ) versus no training , followed by re assessment of performance . RESULTS Initially , there were no significant differences between VR-trained ( n = 9 ) and control ( n = 10 ) groups . After training , object visualization , scope orientation , and horizon error scores were significantly better in VR-trained than control groups ; subject-matched improvement in orientation score was 50.9 % versus 10.8 % ( P < .05 ) . CONCLUSIONS VR training in angled laparoscope use improves operative performance of novices . These data support growing evidence that VR training is highly effective in improving surgical skills outside of the clinical setting TOPIC The rapid development of advanced laparoscopic techniques is a strong challenge for the skills and competence of the paediatric surgeon . It is therefore m and atory that training must offer adequate preparation . The present experimental study investigates how surgical residents perform laparoscopic bowel biopsy and defect repair after training with a pelvitrainer versus a rabbit model . METHODS New Zeal and white rabbits , 3 mm instruments , a 5 mm scope and a 6 - 0 prolene suture were used . Twelve surgical residents were r and omised into two groups . Their basic task was to take a seromuscular bowel biopsy laparoscopically and to repair the defect using an intracorporeal suture . Group I trained 8 times ( on 8 occasions ) with a pelvitrainer ( PT ) , group II trained similarly using a rabbit model ( RM ) . Each participant took a final test to demonstrate the operation in the rabbit . Operating time , suture time and perforation of the bowel were analysed . RESULTS In the PT group , mean operating times decreased from 11.18 ( + /- 5.04 ) min to 4.91 ( + /- 0.89 ) min ( p < 0.01 ) , however the final test procedure in the rabbit model lasted 9.62 ( + /- 5.11 ) min . In the RM group mean operating times also decreased from 10.04 ( + /- 3.39 ) min to 6.38 ( + /- 1.40 ) min ( p < 0.01 ) during the eight training operations . Within this group the final live operation lasted 5.45 ( + /- 0.67 ) min and was significantly faster than in the PT group 9.62 ( + /- 5.11 ) min ( p < 0.1 ) . The suture times showed a similar pattern . A significant difference with respect to the rate of perforation was not found . CONCLUSIONS Repetitive training in the rabbit provides superior skills for live operations . In paediatric surgical centres with advanced laparoscopic procedures , an animal model should be considered as an important step in training which may contribute to a beneficial outcome in patients BACKGROUND This study compares a laparoscopic skill training protocol without proficiency targets to the same protocol with explicit targets and notification of progress . METHODS Fourteen surgery interns were r and omized into 2 groups . The intervention group received task-specific proficiency criteria to guide practice . The control group did not . After training , participants were evaluated by blinded faculty during laparoscopic cholecystectomy . RESULTS The control group met significantly fewer of the 7 LapSim ( Surgical Science Sweden AB , Gotëborg ) targets ( mean = 1.14 ) than the intervention group ( mean = 7.00 ; P = .001 ) and significantly fewer of the 5 video trainer targets ( mean = .86 ) than the intervention group ( mean = 5.00 ; P = .001 ) . Ratings of depth perception , bimanual dexterity , efficiency , tissue h and ling , autonomy , and overall competence were higher for the intervention group . Effect sizes ranged from medium to large ( .394-.981 ) , indicating an impact of the proficiency-based training protocol . CONCLUSIONS Delineation of proficiency targets with reporting of progress improves interns ' practice results , and appears to have a positive effect on their early operating room ( OR ) performance of laparoscopic cholecystectomy Background Psychomotor skills for endoscopic surgery can be trained with virtual reality simulators . Distributed training is more effective than massed training , but it is unclear whether distributed training over several days is more effective than distributed training within 1 day . This study aim ed to determine which of these two options is the most effective for training endoscopic psychomotor skills . Methods Students with no endoscopic experience were r and omly assigned either to distributed training on 3 consecutive days ( group A , n = 10 ) or distributed training within 1 day ( group B , n = 10 ) . For this study the SIMENDO virtual reality simulator for endoscopic skills was used . The training involved 12 repetitions of three different exercises ( drop balls , needle manipulation , 30 ° endoscope ) in differently distributed training schedules . All the participants performed a posttraining test ( posttest ) for the trained tasks 7 days after the training . The parameters measured were time , nontarget environment collisions , and instrument path length . Results There were no significant differences between the groups in the first training session for all the parameters . In the posttest , group A ( training over several days ) performed 18.7 % faster than group B ( training on 1 day ) ( p = 0.013 ) . The collision and path length scores for group A did not differ significantly from the scores for group B. Conclusion The distributed group trained over several days was faster , with the same number of errors and the same instrument path length used . Psychomotor skill training for endoscopic surgery distributed over several days is superior to training on 1 day BACKGROUND The introduction of noninvasive laparoscopic surgery has raised concerns about appropriate teaching techniques for medical students considering surgery as a specialization . The principal aim of this study was to determine the effect , between the sexes , of cognitive imaging as a teaching method in the context of learning a surgical technique . METHODS A r and omized treatment-control sample of 42 medical student volunteers was used to test the effect of cognitive imaging on performance and on traditional instructional techniques to help medical students acquire suturing skills specific to laparoscopic surgery . RESULTS Repeated- measures analysis of variance showed no significant effect for the use of cognitive imaging ( F1,40 = 0.97 , p > 0.05 ) . Males tended to perform better than females in completing tasks that required the use of visual-spatial manipulation of the instruments within a simulated laparoscopic environment ( F1,40 = 5.08 , p < 0.05 ) . CONCLUSIONS These results , which are in concordance with other research findings , indicate that females generally have lower visual-spatial abilities than males . Enhanced performance for both sexes , however , increases rapidly with practice . Other than verbal one-on-one instruction , males on average rank instructional approaches that are applied and visual higher than do females BACKGROUND We have previously shown that reaching expert performance on an fundamentals of laparoscopic surgery (FLS)-type simulator model for laparoscopic suturing results in measurable improvement during an actual operation ; trained novices , however , demonstrate inferior operative performance compared with experts . We hypothesized that simulator training under more difficult and realistic conditions would enhance the operative performance of novices . STUDY DESIGN Medical students ( n=32 ) participated in an IRB-approved , r and omized , controlled trial . All participants were pretested in laparoscopic suturing on a previously vali date d porcine Nissen model and were r and omized into three groups : group I ( n=6 ) received no training , group II ( n=13 ) trained on the FLS videotrainer model until a previously published proficiency score ( 512 ) was achieved on 2 consecutive and 10 additional attempts , group III ( n=13 ) trained to the same goal but had to practice in a constrained space , with a shorter suture , starting with a dropped needle , and listening to operating room noise . Training workload was measured with the vali date d NASA-TLX ( Task Load Index ) question naire after each training session . All groups were posttested on the porcine model . Results were compared using ANOVA ; p < 0.05 was considered significant . RESULTS All group II and III participants reached the training goal . At posttesting , group II and group III participants performed similarly , but substantially better than group I did ( 210+/-140 versus 218+/-139 versus 0+/-0 , respectively ; p < 0.001 ) . Compared with group II , group III participants trained longer ( 329+/-71 minutes versus 239+/-69 minutes , p < 0.001 ) , performed more repetitions ( 81+/-15 versus 59+/-14 , p < 0.001 ) , and their workload improved less by the end of training ( 5 % versus 23 % , p < 0.001 ) . CONCLUSIONS Proficiency-based simulator training reliably results in improved operative performance . Although increasing the level of training difficulty increased trainees ' workload , the strategy we used in this study did not enhance their operative performance . Other methods for curriculum optimization are needed In two experiments we investigated the role of continuous concurrent visual feedback in the learning of discrete movement tasks . During practice the learner 's actions either were or were not displayed on-line during the action ; in both conditions the participant received kinematic feedback about errors afterward . Learning was evaluated in retention tests on the following day . We separated ( a ) errors in the fundamental spatial-temporal pattern controlled by the generalized motor program from ( b ) errors in scaling controlled by parameterization processes . During practice concurrent feedback improved parameterization but tended to decrease program stability . Based on retention tests , earlier practice with continuous feedback generally interfered with the learning of an accurate motor program and reduced the stability of time parameterization . Continuous feedback during acquisition de grade s the learning of not only closed-loop processes in slower movements ( as has been found in earlier studies ) but also motor programs and their parameterization in more rapid tasks . Implication s for feedback in training and simulation are discussed Background Not much is known about the exact role of force feedback in laparoscopy . This study aim ed to determine whether force feedback influences movements of instruments during training in laparoscopic tasks and whether force feedback is required for training in basic laparoscopic force application tasks . Methods A group of 19 gynecologic residents , r and omly divided into two groups , performed three laparoscopic tasks in both the box trainer and the virtual reality ( VR ) trainer . The box-VR group began with the box trainer , whereas the VR-box group began with the VR trainer . The three selected tasks included different levels of force application . The box trainer provides natural force feedback , whereas the VR trainer does not provide force feedback . The performance of the two groups was compared with regard to time , path length , and depth perception . Results For the tasks in which force plays hardly a role , no differences between box-VR group and the VR-box group were found . During a task in which force application ( pulling and pushing forces ) plays a role , the box-VR group outperformed VR-box group in the box trainer . Moreover , training with the box trainer had a positive effect on subsequent performance of the task with the VR trainer . This was not found the other way around . No differences were found between box-VR and the VR-box group in tasks not requiring force application . Conclusion Force feedback influences basic laparoscopic skills during tasks in which pulling and pushing forces are applied . For these tasks , the switch from the trainer without force feedback to the one with natural force feedback has a detrimental effect on performance . Therefore , training for tasks in which forces play an important role ( e.g. , stretching , grasping ) should be done using systems with natural force feedback , whereas eye – h and coordination can be trained without force feedback Background The content validity of currently available inanimate simulation models is question able , because some tasks seem too far from clinical reality . The aim of this study was to vali date a simulation model with six tasks commonly used in clinical practice ( 6-TSM ) for the acquisition of psychomotor skills in minimally invasive surgery ( MIS ) . Methods This was a prospect i ve r and omized trial comparing the 6-TSM to a previously described three-task training method ( 3-TTM ) . All first , second , and third postgraduate year surgical residents were eligible . The 6-TSM included clipping and dividing of a vessel , excision of lesion , appendectomy , mesh repair , suturing perforation , and h and -sewn anastomosis . The outcome measures of 6-TSM included accuracy error , tissue damage , sliding knot , leak , operating time , and dangerous movements . After completion of training , 6-TSM and 3-TTN residents were tested by the Minimally Invasive Surgical Trainer — Virtual Reality ( MIST-VR ) . Criterion-related and construct validity , responsiveness , test – retest , and interrater reliability were assessed . Results During six months , 17 residents underwent training with the 6-TSM or the 3-TTM as allocated . The mean duration of training with 6-TSM and 3-TTM was similar ( 7.8 vs 8.1 h ) . The criterion-related validity of the 6-TSM was shown by significantly increased skill improvement in the 6-TSM residents , as compared with the 3-TTM residents at MIST-VR . Construct validity the of 6-TSM was shown by the finding that the experts ’ baseline was superior to the residents ’ baseline . The responsiveness of the 6-TSM was shown by the significantly increased skill improvement of the 6-TSM residents in sliding knot , leak , and operating time . The test – retest reliability of the 6-TSM was good ( > 0.80 ) , except for accuracy error and dangerous movements ( Cronbach ’s intraclass correlation coefficient α : 0.57 , p < 0.0001 ; 0.62 , p < 0.0001 , respectively ) . The interrater reliability of the 6-TSM was good ( > 0.80 ) except for leak ( Kendall ’s concordance coefficient tau_b:0.76 , p = 0.06 for h and -sewn anastomosis ) and dangerous movements ( tau_b:0.72 , p = 0.08 for suturing perforation and tau_b:0.68 , p = 0.10 for h and -sewn anastomosis ) . The perresident cost for 6-TSM was $ 769 . Conclusions The 6-TSM is a valid and reliable learning tool for surgical residents ’ acquisition of laparoscopic motor skills Background : Laparoscopic suturing is required to develop competency in advanced laparoscopy . Methods : Manuals detailing laparoscopic suturing were give to 17 Surgery residents . One week later they performed a suture on a training model . Time ( s ) , accuracy ( mm ) , and knot strength ( lb ) were recorded . The residents were blindly r and omized to intervention ( n = 9 ) and control ( n = 8) groups . The intervention residents attended a 60-min course with lecture , video , and individual proctoring . Two weeks later they performed a stitch with st and ard laparoscopic instruments and a stitch with a suturing assist device . Statistical analysis included a Wilcoxon rank-sum test . Results : The intervention residents decreased their suturing time from the first to the second stitich ( 732.4–257.6s ) , the control and residents decreased their time from 500.2 s to 421.8 s. The time required to perform the second stitch showed no significant difference between the two groups ( p = 0.46 ) , but the difference in reduced time between the first and second stitch was significant ( p = 0.001 ) . Using the suturing assist device for the third suture , the intervention and control groups both decreased their times significantly . The control residents performed almost as quickly as the intervention residents with the suturing ; device ( p = 0.11 ) . Accuracy and knot strength were not different in any test . Conclusions : Residents can improve suturing skill with a short didactic course and individual proctoring . A suturing assist device decreases time required by inexperienced surgeons to device perform an intracorporeal tie Background Minimally invasive surgery in small children and infants requires special skills and training . This experimental study compares the efficiency of an in vitro pelvic trainer ( PT ) and an a in vivo animal model ( AM ) . Methods For this study , 12 residents were prospect ively r and omized into two groups . Initially , all had to pass a basic skill assessment ( 3 tasks ) . Then endoscopic small bowel biopsy was performed ( 8 times ) either with the in vitro PT ( group A ) or the in vivo AM ( group B ) . Finally , all had to demonstrate this procedure in the in vivo AM and repeat the basic skill assessment . A quality index ( complications , suture , biopsy ) was evaluated . Results Initially , there was no difference between the two groups . Interestingly , the mean regression gradient of the index for the in vitro PT ( group A ) was significantly better than for the in vivo AM ( group B ) . In the final in vivo operation , however , the mean index for the in vitro PT ( group A ) worsened significantly , whereas it increased for the in vivo AM ( group B ) ( p = 0.037 ) . Conclusion Adequate training for an isolated mechanical task such as gut biopsy can be supplied using a pelvic trainer or animal model with similar effects . However in vivo performance of the same task requires secondary surgical skills , which are conveyed during live training with greater success . Consequently , stepwise teaching with both modules seems reasonable before these procedures are approached in neonates or small children Abstract Background : Laparoscopic skills can be measured objective ly in a video-laparoscopic cart simulator system . These scores have been shown to be sufficiently sensitive to distinguish differences in performance between residents at different levels of training . The purpose of this study was to compare a simplified mirrored-box simulator to the video-laparoscopic cart system . Methods : A total of 22 surgical residents performed seven structured tasks in both simulators in r and om order . Scores reflected precision and speed . The tasks were transferring , cutting , clip + divide , looping , mesh placement + fixation , and suturing with intracorporeal and extracorporeal knots . Results : There were no significant differences in mean raw scores between the simulators for six of the seven tasks . Resident total scores correlated well between simulators ( r= 0.68 , p= 0.001 ) . Resident ranking also correlated well ( r= 0.69 , p < 0.001 ) . Conclusions : A mirrored-box simulator was shown to provide a reasonable reflection of relative performance of laparoscopic skills . Practical , effective laparoscopic skills training and evaluation can be accomplished without the need for cumbersome equipment Objective : To evaluate the impact of a cognitive training method on the performance of simulated laparoscopic cholecystectomy in laparoscopic training courses . Summary Background Data : Surgeons are like professional sportsmen in that they have to be able to perform complicated , fine-motor movements under stressful conditions . Mental training , systematic ally and repeatedly imagining a movement 's performance , is a well-established technique in sports science , and this study aim ed to determine its value in training surgeons . Methods : A total of 98 surgeons undergoing basic laparoscopic training participated in a r and omized controlled trial ; 31 received additional mental training , 32 additional practical training , and 35 received no additional training ( control group ) . All used a Pelvi-Trainer simulator to perform laparoscopic cholecystectomy at baseline and follow-up , after any additional intervention . We used a modified Objective Structured Assessment of Technical Skills ( OSATS ) instrument to assess performance . Principle outcome variables were the OSATS task-specific checklist ( 11 procedural steps , scored as correctly [ 1 ] or wrongly [ 0 ] performed ) and the global rating scale ( an overall performance evaluation , scored 1–5 ) . Results : Improvement in the task-specific checklist score between baseline and follow-up differed significantly between groups ( P = 0.046 on ANOVA ) . Least significant difference tests yielded differences between the mental and practical training groups ( P = 0.024 ) and between the mental training and control groups ( P = 0.040 ) , but not between the practical training and control groups ( P = 0.789 ) . Paired Student t test showed that performance at follow-up was significantly better in the mental training and control groups ( mental training group , P = 0.001 ; control group , P = 0.018 ) but not the practical training group ( P = 0.342 ) . There were no significant intergroup differences in global rating scale results . Conclusion : Additional mental training is an effective way of optimizing the outcomes of further training for laparoscopic cholecystectomy . It is associated with fewer costs and with better outcomes in some crucial assessment scales than additional practical training Background In the acquisition of new skills that are difficult to master , such as those required for laparoscopy , feedback is a crucial component of the learning experience . Optimally , feedback should accurately reflect the task performance to be improved and be proximal to the training experience . In surgery , however , feedback typically is in vivo . The development of virtual reality training systems currently offers new training options . This study investigated the effect of feedback type and quality on laparoscopic skills acquisition . Methods For this study , 32 laparoscopic novices were prospect ively r and omized into four training conditions , with 8 in each group . Group 1 ( control ) had no feedback . Group 2 ( buzzer ) had audio feedback when the edges were touched . Group 3 ( voiced error ) had an examiner voicing the word “ error ” each time the walls were touched . Group 4 ( both ) received both the audio buzzer and “ error ” voiced by the examiner All the subjects performed a maze-tracking task with a laparoscopic stylus inserted through a 5-mm port to simulate the fulcrum effect in minimally invasive surgery ( MIS ) . A computer connected to the stylus scored an error each time the edge of the maze was touched , and the subjects were made aware of the error in the aforementioned manner . Ten 2-min trials were performed by the subjects while viewing a monitor . At the conclusion of training , all the subjects completed a 2-min trial of a simple laparoscopic cutting task , with the number of correct and incorrect incisions recorded . Results Group 4 ( both ) made significantly more correct incisions than the other three groups ( F = 12.13 ; df = 3 , 28 ; p < 0.001 ) , and also made significantly fewer errors or incorrect incisions ( F = 14.4 ; p < 0.0001 ) . Group 4 also made three times more correct incisions and 7.4 times fewer incorrect incisions than group 1 ( control ) . Conclusions The type and quality of feedback during psychomotor skill acquisition for MIS have a large effect on the strength of skills generalization to a simple MIS task and should be given serious consideration in curriculum design for surgical training using simulation tasks OBJECTIVE The aim of this study was to compare a simulator with the human cadaver model for h and -assisted laparoscopic colorectal skills acquisition training . DESIGN An observational prospect i ve comparative study was conducted to compare the laparoscopic surgery training models . SETTING The study took place during the laparoscopic colectomy training course performed at the annual scientific meeting of the American Society of Colon and Rectal Surgeons . PARTICIPANTS Thirty four practicing surgeons performed h and -assisted laparoscopic sigmoid colectomy on human cadavers ( n = 7 ) and on an augmented reality simulator ( n = 27 ) . Prior laparoscopic colorectal experience was assessed . Trainers and trainees completed independently objective structured assessment forms . Training models were compared by trainees ' technical skills scores , events scores , and satisfaction . RESULTS Prior laparoscopic experience was similar in both surgeon groups . Generic and specific skills scores were similar on both training models . Generic events scores were significantly better on the cadaver model . The 2 most frequent generic events occurring on the simulator were poor h and -eye coordination and inefficient use of retraction . Specific events were scored better on the simulator and reached the significance limit ( p = 0.051 ) for trainers . The specific events occurring on the cadaver were intestinal perforation and left ureter identification difficulties . Overall satisfaction was better for the cadaver than for the simulator model ( p = 0.009 ) . CONCLUSIONS With regard to skills scores , the augmented reality simulator had adequate qualities for the h and -assisted laparoscopic colectomy training . Nevertheless , events scores highlighted weaknesses of the anatomical replication on the simulator . Although improvements likely will be required to incorporate the simulator more routinely into the colorectal training , it may be useful in its current form for more junior trainees or those early on their learning curve BACKGROUND Proficiency-based training in laparoscopic suturing and knot tying translates to the operating room , but little is known about the durability of acquired skill . The purpose of this study was to determine the effect of maintenance training on skill retention after demonstration of proficiency . STUDY DESIGN Medical students ( n=18 ) with no previous laparoscopic or simulator experience were enrolled in an IRB-approved r and omized controlled trial . All subjects trained to proficiency ( score of 512 , based on time and errors ) on a previously vali date d suturing model ( Fundamentals of Laparoscopic Surgery videotrainer ) . Subjects were then r and omized to a control group , which received no additional training , and an ongoing training group , which trained again to proficiency at 1 and 3 months ( immediately after testing ) . Simulator testing was repeated at 2 weeks , 1 month , 3 months , and 6 months after initial training . No subject had interval operative experience . RESULTS Both groups demonstrated excellent skill retention during followup ; performance scores , reported as means+/-SD , were 488+/-57 versus 482+/-55 at 2 weeks ( p = ns ) , 483+/-81 versus 491+/-64 at 1 month ( p = ns ) , 467+/-75 versus 470+/-67 at 3 months ( p = ns ) , and 462+/-62 versus 492+/-43 at 6 months ( p=0.02 ) for the control versus ongoing training groups , respectively . At 6 months , the ongoing training group showed better skill retention ( 95 % versus 90 % ; p=0.02 ) and a trend for achieving the proficiency level ( 33 % versus 18 % ; p=0.2 ) more often than the control group . CONCLUSIONS Although proficiency-based training results in excellent skill retention , ongoing training substantially enhances performance and minimizes skill loss . Curricula should incorporate training that fosters maintenance of proficiency Background A multifunctional skill trainer ( Berlin Operation Trainer , BOPT ) allows realistic training of conventional gastrointestinal ( GI ) surgical techniques . The aim of this prospect i ve r and omized study was to evaluate the training success and the potential for transfer of anastomotic techniques in GI surgery into the operating room using the BOPT . Methods Thirty-six surgical residents and surgeons in their subspecialty fellowship were classified as novices and experts according to their surgical experience and r and omized into either a group that trained on st and ard training devices ( n = 19 ) or a group that trained on the BOPT ( n = 17 ) . The participants performed an intestinal anastomosis with a single-layer running suture with BOPT ( + BOPT ) or without BOPT ( −BOPT ) at the beginning ( point in time 1 , PIT 1 ) and at the end of 4 days of surgical training ( PIT 2 ) . To simulate a real operation , the anastomosis at PIT 2 was performed in the open situs of an intubated domestic pig . The performance of the intestinal anastomoses was documented with video and photos . The time to perform the anastomosis and the quality of the anastomosis technique ( total enterorrhaphy score ) were rated independently by two surgeons using 17 defined quality criteria . Results The + BOPT group was faster than the control group ( –BOPT group ) ( operating time = 192.4 ± 53.8 vs. 221.3 ± 47.8 s ; P = 0.064 ) and had a higher score ( 12.1 ± 2.0 vs. 10.2 ± 2.6 points ; P = 0.032 ) at PIT 2 . Participants with an improved video and photo enterorrhaphy score had trained more frequently with the BOPT ( + BOPT group ) ( 14/19 , 73.7 % ; P < 0.0005 ) . The participants in the BOPT group showed a significant improvement in performance from PIT 1 to PIT 2 with respect to speed ( P = 0.049 ) , the quality of the suture ( video enterorrhaphy score ; P = 0.026 ) , the completed anastomosis ( photo enterorrhaphy score ; P = 0.021 ) , and the total enterorrhaphy score ( video and photo enterorrhaphy score ; P = 0.039 ) compared to the control group without BOPT . There were no significant differences in improvement between novices and experts . Conclusion The training using the Berlin Operation Trainer ( BOPT ) with respect to training success and the potential to transfer to GI surgery the suture and anastomosis techniques learned seems to be significantly superior to st and ard surgery modules , independent of the surgeon ’s training status . The BOPT is a useful tool for training conventional gastrointestinal surgery techniques BACKGROUND Error recognition predicts technical skill . A curriculum including error recognition may improve laparoscopic suturing performance . METHODS Thirty novices were r and omized into 2 groups . Each viewed an instruction videotape and underwent timed objective structured assessment s of technical skills . Group A practice d the task , group B viewed an error-instruction video , practice d , followed by re- assessment . Participants counted errors on a videotape . Data were analyzed with the Fisher exact text , the Wilcoxon test , and the Kendall tau test . RESULTS The improvement in task time was greater in group A than in group B ( P < .001 ) . The objective structured assessment s of technical skills scores improved for both groups , but did not reveal differences between the groups . Group B recognized significantly more errors than group A ( P < 0.001 ) . CONCLUSIONS The additional error instruction showed a negative impact on performance speed , but improved cognitive error recognition . Whether visual memory overload influenced the outcome requires further examination BACKGROUND The purpose of this study was to determine the impact of instructor feedback and video tutorials on skill acquisition during proficiency-based laparoscopic suturing training . METHODS Performance data from a prospect ively maintained data base were review ed for three groups of novices ( n = 34 medical students ) who completed the same proficiency-based laparoscopic suturing curriculum on a Fundamentals of Laparoscopic Surgery-type videotrainer model as part of two separate institutional review board-approved , r and omized controlled trials . Group I ( n = 9 ) watched the video tutorial once and received intense feedback during each training session ; Group II ( n = 13 ) watched the video tutorial once and received limited feedback ( < 10 min per session ) ; Group III ( n = 12 ) watched the video tutorial several times and also received limited feedback ( < 10 min per session ) . Feedback was given by the same instructor and was quantified on a 0 ( none ) to 4 ( extensive ) Likert scale . RESULTS Baseline characteristics were similar for all groups . All participants achieved the proficiency level ( 512 ) on two consecutive attempts . Group III required the shortest training time and number of repetitions to reach proficiency , with statistically significant differences compared with Group I ( P < 0.02 ) . This strategy led to a cost savings of $ 139 per trainee . CONCLUSIONS Limited instructor feedback appears to be superior to intense feedback during proficiency-based laparoscopic simulator training . Coupled with video tutorials , this type of feedback may accelerate learning and improve re source utilization by minimizing the need for instructor involvement BACKGROUND Laparoscopic suturing is an advanced skill that is difficult to acquire . Simulator-based skills curricula have been developed that have been shown to transfer to the operating room . Currently available skills curricula need to be optimized . We hypothesized that mastering basic laparoscopic skills first would shorten the learning curve of a more complex laparoscopic task and reduce re source requirements for the Fundamentals of Laparoscopic Surgery suturing curriculum . STUDY DESIGN Medical students ( n = 20 ) with no previous simulator experience were enrolled in an IRB-approved protocol , pretested on the Fundamentals of Laparoscopic Surgery suturing model , and r and omized into 2 groups . Group I ( n = 10 ) trained ( unsupervised ) until proficiency levels were achieved on 5 basic tasks ; Group II ( n = 10 ) received no basic training . Both groups then trained ( supervised ) on the Fundamentals of Laparoscopic Surgery suturing model until previously reported proficiency levels were achieved . Two weeks later , they were retested to evaluate their retention scores , training parameters , instruction requirements , and cost between groups using t-test . RESULTS Baseline characteristics and performance were similar for both groups , and 9 of 10 subjects in each group achieved the proficiency levels . The initial performance on the simulator was better for Group I after basic skills training , and their suturing learning curve was shorter compared with Group II . In addition , Group I required less active instruction . Overall time required to finish the curriculum was similar for both groups ; but the Group I training strategy cost less , with a savings of $ 148 per trainee . CONCLUSIONS Teaching novices basic laparoscopic skills before a more complex laparoscopic task produces substantial cost savings . Additional studies are needed to assess the impact of such integrated curricula on ultimate educational benefit BACKGROUND Studies have demonstrated the beneficial effect of training novice laparoscopic surgeons using virtual reality ( VR ) simulators , although there is still no consensus regarding an optimal VR training curriculum . This study aims to establish and vali date a structured VR curriculum to provide an evidence -based approach for laparoscopic training programmes . METHODS The minimally invasive VR simulator ( MIST-VR ) has 12 abstract laparoscopic tasks , each at 3 graduated levels of difficulty ( easy , medium , and hard ) . Twenty medical students completed 2 sessions of all tasks at the easy level , 10 sessions at the medium level , and finally 5 sessions of the 2 most complex tasks at the hard level . At the medium level , subjects were r and omized into 2 equal groups performing either all 12 tasks ( group A ) or the 2 most complex tasks ( group B ) . Performance was measured by time taken , path length , and errors for each h and . The results were compared between groups , and to those of 10 experienced laparoscopic surgeons . RESULTS Baseline performance of both groups was similar at the easy level . At the medium level , learning curves for all 3 parameters reached plateau at the second ( group A , P < .05 ) and sixth ( group B , P < .05 ) repetitions . Performance at the hard level was similar between the 2 groups , and all achieved the pre-set expert criteria . CONCLUSION A graduated laparoscopic training curriculum enables trainees to familiarise , train and be assessed on laparoscopic VR simulators . This study can aid the incorporation of VR simulation into established surgical training programmes To assess the effects of practice and dynamic instruction on changes in speed and accuracy during acquisition of simulated laparoscopic surgical skills . Fourteen PGY-1 general surgery residents were r and omly assigned to 1 of 2 experimental conditions ( n = 7 per group ) , either practice only or practice with instruction , and required to perform 10 trials of each of 2 laparoscopic surgical skills-cannulation and object passing . Practice only subjects were given verbal instructions for each task , and corrective feedback only after trial 1 . Practice with instruction subjects were treated the same , but also saw a videotaped demonstration and received dynamic feedback during and between each trial . Performance speed was recorded for each trial and number of errors was recorded for trials 8 to 10 by videotape review .Mean speed for subjects in both groups increased significantly for both tasks ( p < 0.01 ) . Practice with instruction subjects committed significantly fewer errors on object passing ( p < 0.04 ) and were less variable in the number of errors committed during the cannulation task ( p < 0.01 ) . Practice , with or without dynamic instruction , results in significant improvement in the speed of performance of simulated laparoscopic surgical skills . The addition of dynamic instruction to simulator-based practice improves the quality and consistency of resident acquisition of laparoscopic surgical skills To improve instruction efficiency during advanced laparoscopic surgery , a h and s-free , head-controlled , multimonitor pointer was developed . One instructor guided 20 trainees to locate critical points on a simulated laparoscopic cholecystectomy model . Twenty points , visible to the instructor only , were selected on a photo of a partially dissected gallbladder placed within a laparoscopic trainer box . For each trainee , the points were r and omized to 2 groups of 10 points with the instructor providing verbal guidance only or guidance assisted by the head-controlled pointer that appeared on both the instructor 's and trainees ' monitors . The primary outcome was the time to locate 10 points . Total time was shorter with the pointer than with verbal guidance alone ( 65 ± 14 vs 119 ± 34 seconds , P < .001 ) . The average of mean individual times to locate each point was shorter with the pointer than without ( 5.4 ± 0.5 vs 11.9 ± 2.4 seconds , P < .001 ) . The instructor 's efficiency improved over time with both verbal guidance ( P = .007 ) and with the pointer ( P = .001 ) . The benefit of pointer instruction was greater in trainees with laparoscopic experience compared with those without experience ( P = .006 ) . Use of a h and s-free pointer improved instruction efficiency in simulated laparoscopy . Experienced surgeons benefited the most PURPOSE To create and evaluate the effectiveness of an in vitro training model for laparoscopic urethrovesical anastomosis . MATERIAL S AND METHODS Chicken posterior trunks and porcine colons were used to construct the training model , which was later compared with the chicken skin model . The posterior trunk of a chicken was used to simulate a human pelvis , and a 3-mm cloacal stump was used to simulate a human urethral stump . A 15-cm segment of porcine colon with a 1-cm orifice was used to simulate a human bladder or neobladder . An imitation urethrovesical anastomosis was performed with laparoscopic instruments in a laparoscopic training box . The simulated urethral stump and bladder neck were anastomosed with six interrupted stitches . Forty urologic residents were r and omized into two groups . The residents in group A ( n = 20 ) practice d using this model for 8 hours , while those in group B ( n = 20 ) practice d using the chicken skin model for 8 hours . The residents ' skills were assessed using the porcine model before and after training . RESULTS All residents accomplished the training course and both assessment s. There was no significant difference between the groups in anastomosis time ( 122.65 + /- 19.98 minutes v 120.70 + /- 17.30 minutes , P > 0.05 ) and quality ( 3.80 + /- 1.24 v 3.75 + /- 1.16 , P > 0.05 ) before training . After the training sessions , both groups improved in anastomosis time and quality . Compared with residents in group B , residents in group A required less time ( 63.55 + /- 11.08 minutes v 76.55 + /- 12.46 minutes , P < 0.05 ) and achieved a higher quality score ( 8.80 + /- 1.00 v 7.65 + /- 0.88 , P < 0.05 ) . CONCLUSION This training model more accurately resembles the structure and characteristic of the human pelvis , urethral stump , and bladder ( neobladder ) . In addition , all the material s needed for this model are inexpensive and easily obtained . Therefore , it is an effective , convenient training model for laparoscopic urethrovesical anastomosis BACKGROUND Teaching of technical surgical skills to undergraduate medical students in a laboratory setting away from the patient is not common practice . Because of the large volume of students and shortage of available teaching faculty new methods of teaching must be developed for this group of trainees . In this study we examined the effectiveness of computer-based video training , different types of computer-based motion efficiency feedback ( with and without expert criteria ) , and expert feedback on learning of a basic technical skill in medical students . METHODS Forty-five junior medical students were r and omized into 3 groups and learned suturing and knot-tying skills . Group A received computer-generated feedback about the economy of their movements . Group B received the same motion economy feedback , as well as expert reference values . Group C received verbal feedback from an expert . All groups were pre-tested , allowed 18 practice trials , and post-tested , and their skill retention was retested after 1 month . Performance was assessed by expert analysis using an objective structured analysis of technical skill and by computer analysis ( Imperial College Surgical Assessment Device [ ICSAD ] ) . RESULTS All groups showed improvement from pre-test to post-test . However , only group C showed retention of skill on delayed performance testing . CONCLUSIONS Verbal feedback from an expert instructor led to lasting improvements in technical skills performance . Providing information about motion efficiency did not lead to similar improvements BACKGROUND Virtual reality ( VR ) simulators for laparoscopy and endoscopy may be valuable tools for resident education . However , the cost of such training in terms of trainee and instructor time may vary depending upon whether an independent or proctored approach is employed . METHODS We performed a r and omized controlled trial to compare independent and proctored methods of proficiency-based VR simulator training . Medical students were r and omized to independent or proctored training groups . Groups were compared with respect to the number of training hours and task repetitions required to achieve expert level proficiency on laparoscopic and endoscopic simulators . Cox regression modeling was used to compare time to proficiency between groups , with adjustment for appropriate covariates . RESULTS Thirty-six medical students ( 18 independent , 18 proctored ) were enrolled . Achievement of overall simulator proficiency required a median of 11 hours of training ( range , 6 - 21 hours ) . Laparoscopic and endoscopic proficiency were achieved after a median of 11 ( range , 6 - 32 ) and 10 ( range , 5 - 27 ) task repetitions , respectively . The number of repetitions required to achieve proficiency was similar between groups . After adjustment for covariates , trainees in the independent group achieved simulator proficiency with significantly fewer hours of training ( hazard ratio , 2.62 ; 95 % confidence interval , 1.01 - 6.85 ; p = 0.048 ) . CONCLUSIONS Our study quantifies the cost , in instructor and trainee hours , of proficiency-based laparoscopic and endoscopic VR simulator training , and suggests that proctored instruction does not offer any advantages to trainees . The independent approach may be preferable for surgical residency programs desiring to implement VR simulator training OBJECTIVE To assess the effects of mental practice on surgical performance . BACKGROUND Increasing concerns for patient safety have highlighted a need for alternative training strategies outside the operating room . Mental practice ( MP ) , " the cognitive rehearsal of a task before performance , " has been successful in sport and music to enhance skill . This study investigates whether MP enhances performance in laparoscopic surgery . METHODS After baseline skills testing , 20 novice surgeons underwent training on an evidence -based virtual reality curriculum . After r and omization using the closed envelope technique , all participants performed 5 Virtual Reality ( VR ) laparoscopic cholecystectomies ( LC ) . Mental practice participants performed 30 minutes of MP before each LC ; control participants viewed an online lecture . Technical performance was assessed using video Objective Structured Assessment of Technical Skills-based global ratings scale ( scored from 7 to 35 ) . Mental imagery was assessed using a previously vali date d Mental Imagery Question naire . RESULTS Eighteen participants completed the study . There were no intergroup differences in baseline technical ability . Learning curves were demonstrated for both MP and control groups . Mental practice was superior to control ( global ratings ) for the first LC ( median 20 vs 15 , P = 0.005 ) , second LC ( 20.5 vs 13.5 , P = 0.001 ) , third LC ( 24 vs 15.5 , P < 0.001 ) , fourth LC ( 25.5 vs 15.5 , P < 0.001 ) and the fifth LC ( 27.5 vs 19.5 , P = 0.00 ) . The imagery for the MP group was also significantly superior to the control group across all sessions ( P < 0.05 ) . Improved imagery significantly correlated with better quality of performance ( ρ 0.51–0.62 , Ps < 0.05 ) . CONCLUSIONS This is the first r and omized controlled study to show that MP enhances the quality of performance based on VR laparoscopic cholecystectomy . This may be a time- and cost-effective strategy to augment traditional training in the OR thus potentially improving patient care Background : Virtual reality ( VR ) simulators now have the potential to replace traditional methods of laparoscopic training . The aim of this study was to compare the VR simulator with the classical box trainer and determine whether one has advantages over the other . Methods : Twenty four novices were tested to determine their baseline laparoscopic skills and then r and omized into the following three group : LapSim , box trainer , and no training ( control ) . After 3 weekly training sessions lasting 30-min each , all subjects were reassessed . Assessment included motion analysis and error scores . Nonparametric tests were applied , and p < 0.05 was deemed significant . Results : Both trained groups made significant improvements in all parameters measured ( p < 0.05 ) . Compared to the controls , the box trainer group performed significantly better on most of the parameters , whereas the LapSim group performed significantly better on some parameters . There were no significant differences between the LapSim and box trainer groups . Conclusions : LapSim is effective in teaching skills that are transferable to a real laparoscopic task . However , there appear to be no substantial advantages of one system over the other Reverse alignment ( mirror image ) visualization is a disconcerting situation occasionally faced during laparoscopic operations . This occurs when the camera faces back at the surgeon in the opposite direction from which the surgeon ’s body and instruments are facing . Most surgeons will attempt to optimize trocar and camera placement to avoid this situation . The authors ’ objective was to determine whether the intentional use of reverse alignment visualization during laparoscopic training would improve performance . A st and ard box trainer was configured for reverse alignment , and 34 medical students and junior surgical residents were r and omized to train with either forward alignment ( DIRECT ) or reverse alignment ( MIRROR ) visualization . Enrollees were tested on both modalities before and after a 4-week structured training program specific to their modality . Student ’s t test was used to determine differences in task performance between the 2 groups . Twenty-one participants completed the study ( 10 DIRECT , 11 MIRROR ) . There were no significant differences in performance time between DIRECT or MIRROR participants during forward or reverse alignment initial testing . At final testing , DIRECT participants had improved times only in forward alignment performance ; they demonstrated no significant improvement in reverse alignment performance . MIRROR participants had significant time improvement in both forward and reverse alignment performance at final testing . Reverse alignment imaging for laparoscopic training improves task performance for both reverse alignment and forward alignment tasks . This may be translated into improved performance in the operating room when faced with reverse alignment situations . Minimal lab training can account for drastic adaptation to this environment |
734 | 22,258,853 | Conclusion Pemetrexed-based doublet therapy did n’t gain any benefit in survival but significantly improved PFS and better ORR compared with single-agent pemetrexed as second-line therapy for advanced non-small-cell lung cancer .
However , more incidences of grade 3 or 4 neutropenia , thrombocytopenia , and leucopenia were observed in pemetrexed-based doublet group | null | null |
735 | 20,091,562 | There was no significant difference detected in neonatal mortality or neurodevelopmental outcome at two years between infants treated with ethamsylate and controls .
There were no adverse effects of ethamsylate identified from this systematic review .
Preterm infants treated with ethamsylate showed no reductions in mortality or neurodevelopmental impairment despite the reduction in any grade of intraventricular haemorrhage seen in infants < 35 weeks gestation | BACKGROUND Ethamsylate decreases blood loss in certain clinical situations such as menorrhagia and following some surgical procedures .
This potential to reduce bleeding has led to the hypothesis that it may have a role to play in reducing intraventricular haemorrhage in preterm infants .
OBJECTIVES To determine if ethamsylate , when compared to placebo or no treatment , reduces morbidity and /or mortality in preterm infants . | AIM To assess the role of etamsylate * in reducing the risk of haemorrhagic brain damage and its consequences . DESIGN Follow up of babies recruited into a r and omised controlled trial . METHODS A total of 334 infants born before 33 weeks gestation in France and Greece were r and omly allocated within the first four hours of birth either to receive etamsylate or to act as controls . The principal outcomes in the trial were death or impairment and /or disability at the age of 2 years . RESULTS Fifty nine children were lost to follow up . A total of 115 ( 34 % ) either died or had some impairment or disability , and 88 ( 26 % ) either died or had severe impairment or disability at 2 years of age . These outcomes did not differ significantly between the two r and omised groups : relative risks and 95 % confidence intervals 1.14 ( 0.78 to 1.4 ) and 1.17 ( 0.82 to 1.68 ) respectively . The findings were similar for all the prespecified subgroup analyses stratified by key prognostic factors at trial entry : country of birth , gestational age < or ⩾ 29 weeks , inborn or outborn , age < or ⩾ 1 hour , and with or without cerebral scan abnormality . CONCLUSION These findings do not support the use of etamsylate . Other strategies need to be evaluated for the prevention of mortality and morbidity in these vulnerable infants . Key messages The findings from the only published follow up of children from a r and omised controlled trial of etamsylate do not support its use when given within the first four hours of birth to infants born before 33 weeks gestation Centres in Greece and France recruited 334 infants into the trial , and did not find that etamsylate reduced the risk of haemorrhagic brain damage or its consequences in terms of death or impairment and /or disability Other strategies need to be evaluated for the prevention of mortality and morbidity in these vulnerable Cerebral blood flow velocity and cardiac output were measured with ultrasound before and 30 minutes after the administration of ethamsylate in a double blind placebo controlled study of 19 very low birthweight infants . No differences were found before or after treatment in either group Objective : To compare neurodevelopmental outcome of survivors of the multicentre trial of etamsylate ( the iRNN for ethamsylate ) for prevention of periventricular haemorrhage in very low birthweight infants . Design : Double blind , single observer , prospect i ve follow up of placebo controlled study . Setting : Six neonatal intensive care units in the United Kingdom . Neurodevelopmental outcome was assessed in health premises or children ’s homes . Subjects : 268 of 276 survivors of the original study were seen between 3.5 and 4.2 years of age . All were inborn and weighed 1500 g or less at birth . Intervention : Etamsylate 12.5 mg/kg or placebo six hourly from within one hour of delivery for four days . Main outcome measures : McCarthy scales of children ’s abilities , st and ardised neurological examination , full physical examination , functional assessment , seven letter Stycar vision test , and audiometry . Results : There was no difference between the groups in neuromotor outcome ( cerebral palsy ) or in the general cognitive index ( GCI ) of the McCarthy scales ( mean GCI was 93.3 for the etamsylate group ( n = 133 ) and 89.7 for the placebo group ( n = 131 ) ; p = 0.10 ) . There were more children with GCI < 70 ( 9 v 19 ; p = 0.047 ) or ⩽ 50 ( 3 v 11 ; p = 0.03 ) in the placebo group . Fewer children in the etamsylate group had squints ( 17 v 30 ; p = 0.042 ) or required surgery for patent ductus arteriosus ( 1 v 8 ; p = 0.036 ) . Conclusions : Etamsylate was not associated with a reduction in cerebral palsy . Severe cognitive impairment was reduced , but more children died and the improvement may be because fewer survived with low GCI The effect of Dicynene on blood loss during and after transurethral resection for benign enlargement of the prostate was studied in 76 patients . Median loss of blood at operation was 17 ml in those given Dicynene compared with 72 ml in the placebo group ( p equals less than 0.001 ) . Median postoperative blood loss was 38 ml in the Dicynene group , and 103 ml in the placebo group ( p equals 0.05 ) . Clinical evidence of deep vein thrombosis was found in neither group . Dicynene helps to reduce blood loss in transurethral resection The effectiveness of ethamsylate in the prevention of periventricular haemorrhage ( PVH ) in very low birthweight infants was evaluated by means of a multicentre , placebo-controlled , double-blind trial . In 330 infants without evidence of PVH on initial cranial ultrasound examination there was little difference between ethamsylate and placebo groups with respect to subependymal haemorrhage , but intraventricular and parenchymal haemorrhages developed in 30/162 infants ( 18.5 % ) in the treated group , compared with 50/168 ( 29.8 % ) in the control group ( p less than 0.02 ) . The incidence of intraventricular and parenchymal haemorrhage in survivors was 20/137 ( 14.6 % ) in the ethamsylate group and 37/146 ( 25.3 % ) in the controls ( p less than 0.05 ) . In 30 infants with evidence of PVH on the initial scan , ethamsylate treatment seemed to limit parenchymal extension . Analysis of the total cohort of 360 infants showed that the proportion of infants in whom an increase of two or more grade s of severity of PVH was recorded during the trial was lower in the treated than in the placebo group ( p less than 0.01 ) . No adverse effects were attributed to ethamsylate therapy . The reported incidence of patent ductus arterious was lower in the treated than in the placebo group ( p less than 0.02 ) . Mortality was similar in the two groups 22 patients complaining of primary menorrhagia or menorrhagia associated with an intrauterine device ( I.U.C.D. ) were studied in a double blind trial with crossover of ethamsylate and placebo . Acutal menstrual blood-losses were calculated from the iron content of used sanitary material during one pre-trail menstrual period and four trial menstrual periods , during which patients received ethamsylate ( " Dicynene " ) treatment during two menstrual cycles and placebo during two cycles . During ethamsylate treatment the mean menstrual blood-loss was reduced by 50 % in patients with primary menorrhagia and by 19 % in patients with an I.U.C.D. This difference between the two groups is probably accounted for by the differing values of initial blood-loss which was significantly higher in the group with primary menorrhagia . Tampon usage and the duration of bleeding were not significantly altered by ethamsylate treatment . Reported side-effects , which were not serious , were equally common during ethamsylate and placebo treatment OBJECTIVE To determine the role of ethamsylate in prevention of PVH-IVH in premature infants < 34 weeks gestational age . DESIGN Prospect i ve , r and omized , controlled study . METHODS Infants less than 34 weeks gestational age were included in the trial . Neonates with congenital malformations , family history of bleeding disorders and with Apgar scores < 5 at 5 minutes were excluded . Subjects were r and omized into two groups -- Group A infants received intravenous ethamsylate ( 12.5 mg/kg ) six hourly for four days and Group B infants served as a control group . Regular cranial ultrasounds to detect the presence of PVH-IVH were done between days 3 - 5 , 10 - 14 and 28 - 30 of post natal age , and before hospital discharge in all infants and weekly in infants detected to have PVH-IVH on earlier scans . Various antenatal and postnatal factors known to affect the incidence of PVH-IVH were recorded . RESULTS A total of 192 infants underwent the trial , 93 in Group A and 99 in Group B. Antenatal corticosteroids ( 1 or 2 doses ) were administered to 32 ( 34.4 % ) and 36 ( 36.3 % ) women in Group A and Group B , respectively . None of the mothers received phenobarbitone , vitamin K or indomethacin antenatally and none of the infants received phenobarbitone , vitamin E or indomethacin postnatally during the study period . PVH-IVH was seen in 26 infants in Group A , of which Grade I IVH occurred in 9 , Grade II in 14 , Grade III in 2 and Grade IV in one infant . Twenty-nine infants had PVH-IVH in Group B of which 11 had Grade I , 15 Grade II and 3 Grade III . None of the differences were statistically significant . CONCLUSION Postnatal administration of ethamsylate did not decrease the incidence of PVH-IVH in the study infants Some trials in premature infants with respiratory distress syndrome have shown an increased incidence of patent ductus arteriosus after exogenous surfactant therapy . The effect of prophylactic ethamsylate on patent ductus arteriosus after intratracheal administration of a single dose of porcine surfactant preparation ( Curosurf , 2.5 ml/kg ) was studied in a group of 20 preterm infants with severe respiratory distress syndrome . Gestational age of the patients was 29.2 + /- 2.5 weeks ( mean + /- SD ) , and birth weight was 1158 + /- 319 gm . Ethamsylate ( 12.5 mg/kg ) was given prophylactically within the first 4 hours of life followed by 6-hourly doses for 4 days . Hemodynamically significant patent ductus arteriosus occurred more frequently in the untreated group ( 8 of 10 ) than in the ethamsylate group ( 2 of 10 ) ( p < 0.02 ) . No acute adverse effects were attributed to the therapy . This preliminary experience suggests that ethamsylate , an inhibitor of prostagl and in bio synthesis , could be useful in reducing the incidence of patent ductus arteriosus in very low birth weight infants treated with exogenous surfactant Abstract The effect of ethamsylate , a capillary-stabilising drug , in limiting or preventing periventricular haemorrhage ( PVH ) in 70 very low birth-weight babies was evaluated in a double-blind trial . PVH developed in 9 of the 35 infants on ethamsylate and 18 of the 35 infants who received placebo . Mortality associated with PVH was similar in both groups , but the incidence of PVH of all grade s in survivors was reduced in the ethamsylate-treated group OBJECTIVES To determine whether the current incidence of intraventricular haemorrhage ( IVH ) of grade 2 or more is high enough in preterm infants born after 29 weeks gestation to justify the cost of screening with ultrasound and to explore clinical indicators for risk of IVH in the more mature preterm infant . METHODS This cohort study examined the incidence and severity of IVH in 800 preterm infants born between January 1992 and August 1996 , of whom 436 were born after 29 weeks . Demographic and clinical details were collected from a prospect ively maintained data base . The Medicare schedule charge rate for cerebral ultrasound was used to calculate costs . RESULTS 1.1 % of preterm babies born after 29 weeks gestation who had routine ultrasound scans had an IVH of grade 2 or 3 , no infant had a grade 4 IVH . Two infants had a grade 3 IVH , both of which were symptomatic . IVH was poorly predicted by other clinical criteria . Using the Medicare schedule to estimate costs , detecting the five grade 2 or 3 IVH cost A$ 42,000 . CONCLUSIONS The incidence of grade 2 - 4 IVH is low in infants born after 29 weeks gestation . Screening of this population is expensive and probably not justified . It may be most appropriate to scan these infants only if their condition raises concern Patent ductus arteriosus ( PDA ) is common in premature infants younger than 33 weeks ' gestational age ( GA ) , and its deleterious effects are increased by the presence of respiratory distress syndrome . A significant proportion of infants younger than 33 weeks ' GA have PDA . 12 Indomethacin has been used for the treatment of hemodynamically significant ductus , causing severe side effects , but even recently , it has been considered the only pharmacological approach to PDA . 3 In the early 1980s , Morgan et al 4 reported a reduction in the incidence of intraventricular hemorrhages in preterm neonates treated with ethamsylate , an inhibitor of prostagl and in bio synthesis . 4 - 6 Recently , ethamsylate has been reported to favor the closure of the ductus in preterm neonates with respiratory distress syndrome treated with exogenous surfactant . 7 In 1987 , we started prophylaxis of cerebral hemorrhages with ethamsylate ( 50 mg/kg per day in four intramuscular injections for 4 days , from the first day |
736 | 25,686,212 | AND RELEVANCE The pooled evidence suggests that rTMS improves motor symptoms for patients with PD .
Combinations of rTMS site and frequency as well as the number of rTMS pulses are key modulators of rTMS effects . | IMPORTANCE Repetitive transcranial magnetic stimulation ( rTMS ) is a noninvasive neuromodulation technique that has been closely examined as a possible treatment for Parkinson disease ( PD ) .
However , results evaluating the effectiveness of rTMS in PD are mixed , mostly owing to low statistical power or variety in individual rTMS protocol s. OBJECTIVES To determine the rTMS effects on motor dysfunction in patients with PD and to examine potential factors that modulate the rTMS effects . | We evaluated the effect of low-frequency rTMS on motor signs in Parkinson 's disease ( PD ) , under a double-blind placebo-controlled trial design . PD patients were r and omly assigned to received either real ( n = 9 ) or sham ( n = 9 ) rTMS for 10 days . Each session comprises two trains of 50 stimuli each delivered at 1 Hz and at 90 % of daily rest motor threshold using a large circular coil over the vertex . The effect of the stimulation , delivered during the ON-period , was evaluated during both ON and OFF periods . Tests were carried out before and after the stimulation period , and again 1 week after . The effect of the stimulation was evaluated through several gait variables ( cadence , step amplitude , velocity , the CV(stride-time ) , and the turn time ) , h and dexterity , and also the total and motor sections of the UPDRS . Only the total and motor section of the UPDRS and the turn time during gait were affected by the stimulation , the effect appearing during either ON or OFF evaluation , and most importantly , equally displayed in both real and sham group . The rest of the variables were not influenced . We conclude the protocol of stimulation used , different from most protocol s that apply larger amount of stimuli , but very similar to some previously reported to have excellent results , has no therapeutic value and should be ab and oned . This contrasts with the positive reported effects using higher frequency and focal coils . Our work also reinforces the need for sham stimulation when evaluating the therapeutic effect of rTMS OBJECTIVE Several studies have shown that repetitive transcranial magnetic stimulation ( rTMS ) over the dorsolateral prefrontal cortex ( DLPFC ) is effective in the treatment of depression in patients with Parkinson disease ( PD ) . However , since research into the effect of this type of rTMS regime on motor function is limited , we studied the effect of rTMS over the DLPFC on the motor functions in PD patients . METHODS Thirteen patients were r and omly assigned into 2 groups , one receiving real-rTMS ( 90 % of resting motor threshold , 10 Hz , 450 pulses-day for 10 consecutive days ) over the DLPFC contralateral to the more affected side , and the other group receiving sham-rTMS . Assessment included a clinical motor evaluation using part III of the Unified Parkinson 's Disease Rating Scale ( UPDRS ) , and several motor tasks . The UPDRS was applied before and after 10 days of rTMS . Finger tapping , reach movement , grip movement and gait were measured in each session before and after the rTMS over the 10 day period . RESULTS Statistical analysis ( ANOVA for repeated measures ; group * day * side * rTMS ) only showed a significant effect for finger tapping , reach movement and gait for the factor day . No significant change was reported for the UPDRS in any group . CONCLUSIONS Application of rTMS over the DLPFC as a 10 day course had no significant effect on motor functions and clinical motor status , and the improvement in performance of motor tasks can be attributed to the effects of practice . SIGNIFICANCE rTMS over the DLPFC did not lead to any motor improvement in PD patients Objective . To investigate the safety and efficacy of 50-Hz repetitive transcranial magnetic stimulation ( rTMS ) in the treatment of motor symptoms in Parkinson disease ( PD ) . Background . Progression of PD is characterized by the emergence of motor deficits that gradually respond less to dopaminergic therapy . rTMS has shown promising results in improving gait , a major cause of disability , and may provide a therapeutic alternative . Prior controlled studies suggest that an increase in stimulation frequency might enhance therapeutic efficacy . Methods . In this r and omized , double blind , sham-controlled study , the authors investigated the safety and efficacy of 50-Hz rTMS of the motor cortices in 8 sessions over 2 weeks . Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia , Unified Parkinson ’s Disease Rating Scale ( UPDRS ) , and additional clinical , neurophysiological , and neuropsychological parameters . In addition , the safety of 50-Hz rTMS was tested with electromyography-electroencephalogram ( EMG-EEG ) monitoring during and after stimulation . Results . The authors investigated 26 patients with mild to moderate PD : 13 received 50-Hz rTMS and 13 sham stimulation . The 50-Hz rTMS did not improve gait , bradykinesia , and global and motor UPDRS , but there appeared a short-lived “ on”-state improvement in activities of daily living ( UPDRS II ) . The 50-Hz rTMS lengthened the cortical silent period , but other neurophysiological and neuropsychological measures remained unchanged . EMG/EEG recorded no pathological increase of cortical excitability or epileptic activity . There were no adverse effects . Conclusion . It appears that 50-Hz rTMS of the motor cortices is safe , but it fails to improve motor performance and functional status in PD . Prolonged stimulation or other techniques with rTMS might be more efficacious but need to be established in future research Based on several open-label and case studies , repetitive transcranial magnetic stimulation ( rTMS ) seems to have an antidepressive effect on patients with Parkinson 's disease ( PD ) . However , this hypothesis requires further confirmation . We conducted a r and omized , double-blind placebo-controlled study to evaluate the effect of rTMS over the left dorsolateral prefrontal cortex ( DLPFC ) on depression and various motor and nonmotor features of PD . Twenty-two PD patients with mild or moderate depressive episodes were assigned into two groups , one receiving real-rTMS ( 90 % of resting motor threshold , 5 Hz , 600 pulses-a-day for 10 days ) over the left DLPFC , and another group receiving sham-rTMS . An investigator blinded to the treatment performed three video-taped examinations on each patient : before stimulation ( baseline ) , 1 day ( short term ) , and 30 days after treatment session ended ( long-term effect ) . Mini-Mental State Examination , Unified Parkinson 's Disease Rating Scale ( UPDRS ) , Hoehn-Yahr , Epworth Sleepiness , Visual Analog and Montgomery-Asberg Depression Rating Scales ( MADRS ) , Beck Depression Inventory ( BDI ) , and Trail making and Stroop tests were applied . In the actively treated group , not only depression rating scales showed significant improvement 30 days after treatment ended ( BDI by 44.4 % and MADRS by 26.1 % ) , but also the accuracy of Stroop test ( by 16 % ) . We could also demonstrate an insignificant improvement in UPDRS-III by 7.5 points ( 31.9 % , P = 0.06 ) . In the sham-treated group none of the examined tests and scales improved significantly after sham stimulation . Our study demonstrated the beneficial effect of the left DLPFC rTMS on depression in PD lasting at least 30 days after treatment . However , this result should be confirmed in patients with severe depression by further clinical trials The aim of the present study was to investigate the effects of one session of high-frequency repetitive transcranial magnetic stimulation ( rTMS ) applied over the left dorsal premotor cortex ( PMd ) and left dorsolateral prefrontal cortex ( DLPFC ) on choice reaction time in a noise-compatibility task , and cognitive functions in patients with Parkinson ’s disease ( PD ) . Clinical motor symptoms of PD were assessed as well . Ten patients with PD entered a r and omized , placebo-controlled study with a crossover design . Each patient received 10 Hz stimulation over the left PMd and DLPFC ( active stimulation sites ) and the occipital cortex ( OCC ; a control stimulation site ) in the OFF motor state , i.e. at least after 12 h of dopaminergic drugs withdrawal . Frameless stereotaxy was used to target the optimal position of the coil . For the evaluation of reaction time , we used a noise-compatibility paradigm . A short battery of neuropsychological tests was performed to evaluate executive functions , working memory , and psychomotor speed . Clinical assessment included a clinical motor evaluation using part III of the Unified Parkinson ’s Disease Rating Scale . Statistical analysis revealed no significant effect of rTMS applied over the left PMd and /or DLPFC in patients with PD in any of the measured parameters . In this study , we did not observe any effect of one session of high frequency rTMS applied over the left PMd and /or DLPFC on choice reaction time in a noise-compatibility task , cognitive functions , or motor features in patients with PD . rTMS applied over all three stimulated areas was well tolerated and safe in terms of the cognitive and motor effects Dysfunction of the basal ganglia-thalamocortical motor circuit is a fundamental model to account for motor symptoms in Parkinson 's disease ( PD ) . Using high-frequency repetitive transcranial magnetic stimulation ( rTMS ) over the supplementary motor area ( SMA ) , we investigated whether modulation of SMA excitability engenders therapeutic effects on motor symptoms in PD . In this double-blind placebo-controlled study , 99 patients were enrolled and assigned r and omly to SMA-stimulation and sham-stimulation groups . For SMA stimulation , 20 trains of 50 transcranial magnetic stimuli at 5 Hz were delivered at an intensity of 110 % active motor threshold for leg muscles in one session . The sham stimulation was 20 trains of electric stimuli given through electrodes fixed on the head to mimic the cutaneous sensation during rTMS . Each session of intervention was carried out once a week for the first 8 weeks . The SMA stimulation , in contrast to the sham stimulation , engendered significant improvements in total scores and motor scores of the Unified Parkinson 's Disease Rating Scale . Mean improvements in motor scores were 4.5 points in the SMA-stimulation group and -0.1 points in the sham-stimulation group . Results indicate that 5 Hz rTMS over SMA modestly improves motor symptoms in PD patients ; SMA is a potential stimulation site for PD treatment QUESTIONS Does the PEDro scale measure only one construct ie , the method ological quality of clinical trials ? What is the hierarchy of items of the PEDro scale from least to most adhered to ? Is there any effect of year of publication of trials on item adherence ? Are PEDro scale ordinal scores equivalent to interval data ? DESIGN Rasch analysis of two independent sample s of 100 clinical trials from the PEDro data base scored using the PEDro scale . RESULTS Both sample s of PEDro data showed fit to the Rasch model with no item misfit . The PEDro scale item hierarchy was the same in both sample s , ranging from the most adhered to item r and om allocation , to the least adhered to item therapist blinding . There was no differential item functioning by year of publication . Original PEDro ordinal scores were highly correlated with transformed PEDro interval scores ( r = 0.99 ) . CONCLUSION The PEDro scale is a valid measure of the method ological quality of clinical trials . It is valid to sum PEDro scale item scores to obtain a total score that can be treated as interval level measurement and subjected to parametric statistical analysis OBJECTIVE To assess the effects of focal motor cortex stimulation on motor performance and cortical excitability in patients with Parkinson 's disease ( PD ) . METHODS Repetitive transcranial magnetic stimulation ( rTMS ) was performed on the left motor cortical area corresponding to the right h and in 12 ' off-drug ' patients with PD . The effects of subthreshold rTMS applied at 0.5 Hz ( 600 pulses ) or at 10 Hz ( 2000 pulses ) using a ' real ' or a ' sham ' coil were compared to those obtained by a single dose of l-dopa . The assessment included a clinical evaluation by the Unified Parkinson 's Disease Rating Scale and timed motor tasks , and a neurophysiological evaluation of cortical excitability by single- and paired-pulse TMS techniques . RESULTS ' Real ' rTMS at 10 or 0.5 Hz , but not ' sham ' stimulation , improved motor performance . High-frequency rTMS decreased rigidity and bradykinesia in the upper limb contralateral to the stimulation , while low-frequency rTMS reduced upper limb rigidity bilaterally and improved walking . Concomitantly , 10 Hz rTMS increased intracortical facilitation , while 0.5 Hz rTMS restored intracortical inhibition . CONCLUSIONS Low- and high-frequency rTMS of the primary motor cortex lead to significant but differential changes in patients with PD both on clinical and electrophysiological grounds . The effects on cortical excitability were opposite to previous observations made in healthy subjects , suggesting a reversed balance of cortical excitability in patients with PD compared to normals . However , the underlying mechanisms of these changes remain to determine , as well as the relationship with clinical presentation and response to l-dopa therapy . SIGNIFICANCE The present study gives some clues to appraise the role of the primary motor cortex in PD . Clinical improvement induced by rTMS was too short-lasting to consider therapeutic application , but these results support the perspective of the primary motor cortex as a possible target for neuromodulation in PD OBJECTIVE To determine whether low-frequency repetitive transcranial magnetic stimulation ( rTMS ) may modulate l-DOPA-induced dyskinesia ( LID ) in dyskinetic Parkinson 's disease ( PD ) patients . LID is a severe motor complication in advanced PD patients . The neural mechanisms involved in LID are not clear , and it is apparent that both an excessive decrease in internal pallidus firing and a modification and overactivation of cortical motor and premotor areas are involved in its pathogenesis . METHODS Using low frequency 1Hz repetitive rTMS we investigated whether decrease of excitability of the supplementary motor area ( SMA ) may result in modification of LID in PD patients . Furthermore we tested whether it was possible to enhance and /or prolong the beneficial effects of the treatment with repeated sessions of stimulation . RESULTS We observed that 1Hz rTMS induced a transient reduction of dyskinesias . A single session of rTMS improved LID , while repeated sessions of stimulation failed to enhance and /or prolong the beneficial effects of the procedure , without causing motor deterioration or other adverse effects . CONCLUSIONS These results suggest that LID may depend on an increased excitability of the SMA . SIGNIFICANCE SMA rTMS is effective in reducing transiently LID , although can not yet be considered clinical ly useful Objective : To explore the efficacy and stimulation frequency dependence of repetitive transcranial magnetic stimulation ( rTMS ) over the supplementary motor area ( SMA ) in Parkinson disease ( PD ) . Methods : In this r and omized , double-blind , sham-controlled , multicenter study with a parallel design , a weekly intervention was performed 8 times . The effects were monitored up to 20 weeks . By central registration , participants were assigned to 1 of 3 arms of the study : low-frequency ( 1-Hz ) rTMS , high-frequency ( 10-Hz ) rTMS , and realistic sham stimulation . The primary end point was the score change of the Unified Parkinson 's Disease Rating Scale ( UPDRS ) part III from the baseline . Several nonmotor symptom scales such as the Hamilton Rating Scale for Depression , apathy score , and nonmotor symptoms question naire were defined as secondary end points . Results : Of the 106 patients enrolled , 36 were allocated to 1-Hz rTMS , 34 to 10-Hz rTMS , and 36 to realistic sham stimulation . Results show 6.84-point improvement of the UPDRS part III in the 1-Hz group at the last visit of the 20th week . Sham stimulation and 10-Hz rTMS improved motor symptoms transiently , but their effects disappeared in the observation period . Changes in nonmotor symptoms were not clear in any group . No severe adverse event was reported . Conclusions : The 1-Hz rTMS over the SMA was effective for motor , but not nonmotor , symptoms in PD . Level of evidence : This study provides Class I evidence that 1-Hz rTMS over the SMA is effective for motor symptoms in PD Parkinson ’s disease is a movement disorder whose principal symptoms are tremor , rigidity , bradykinesia and postural instability . Initially , drugs like l-dopa or dopaminergic agonists are able to control these symptoms , but with the progress of the disease these drugs become less effective . Previous studies have reported that repetitive transcranial magnetic stimulation ( rTMS ) can improve these motor symptoms . The objective of this study was to investigate the neural mechanisms through which 25 Hz rTMS may improve motor symptoms in Parkinson ’s disease . In a double-blind placebo-controlled study , we evaluated the effects of 25 Hz . rTMS in 10 Parkinson ’s disease patients . Fifteen rTMS sessions were performed over the primary cortex on both hemispheres ( one after the other ) during a 12-week period . The patients were studied using functional magnetic resonance imaging during performance of a simple tapping and a complex tapping task , 1 week before the administration of the first rTMS session and just after the last session . rTMS improved bradykinesia , while functional magnetic resonance imaging showed different cortical patterns in prefrontal cortex when patients performed the complex tapping test . Furthermore , the improvement in bradykinesia is associated with cau date nucleus activity increases in simple tapping . Finally , we observed a relative change in functional connectivity between the prefrontal areas and the supplementary motor area after rTMS . These results show a potential beneficial effect of repetitive transcranial magnetic stimulation on bradykinesia in Parkinson ’s disease which is substantiated by neural changes observed in functional magnetic resonance imaging BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . BACKGROUND Repetitive transcranial magnetic stimulation ( rTMS ) has been reported to be clinical ly effective for treating motor symptoms in Parkinson 's disease ( PD ) . Few studies have been performed reporting the effects of rTMS on non-motor symptoms such as depression and apathy in PD . OBJECTIVE We assessed the effects of high-frequency ( HF ) rTMS over the primary motor ( M1 ) foot area on motor symptoms , depression and apathy scales , and sensory symptoms in PD . METHODS We investigated the efficacy of 3 consecutive days of HF-rTMS over the M1 foot area in 21 patients with PD using a r and omized , double-blind cross-over trial compared with sham stimulation . Motor effects were evaluated using the Unified Parkinson 's Disease Rating Scale part III ( UPDRS-III ) , the self- assessment motor score , the visual analog scale ( VAS ) , the 10-m walking test , and finger tapping . Non-motor effects were analyzed using the Montgomery Asberg Depression Rating Scale , the Apathy Scale , and quantitative sensory testing . RESULTS HF-rTMS significantly improved UPDRS-III ( P < 0.001 ) , VAS ( P < 0.001 ) , the walking test ( P = 0.014 ) , self- assessment motor score ( P = 0.010 ) , and finger tapping measurement ( P < 0.05 ) compared to sham stimulation . In contrast , no significant improvement was observed in depression and apathy scales . Consecutive days of rTMS did not significantly increase the improvement in motor symptoms . There were no adverse effects following rTMS on patients with PD . CONCLUSIONS We confirmed that HF-rTMS over the M1 foot area significantly improved motor symptoms in patients with PD . In addition , daily repeated stimulation was not significantly more effective than a single session of stimulation , but may be effective for maintaining the improvement in motor symptoms in patients with PD Abstract The therapeutic effect of repetitive transcranial magnetic stimulation ( rTMS ) on clinical performance was assessed by a double-blind study in 9 patients with Parkinson 's disease ( PD ) . Nine other patients underwent sham stimulation as controls . The modified Hoehn and Yahr ( H&Y ) staging scale , the Schwab and Engl and Activities of Daily Living ( ADL ) scale , and the Unified Parkinson 's disease rating scale ( UPDRS ) were used to assess changes of clinical performance . Patients were assessed prior to and following 2 months of rTMS . In addition , the mechanism of rTMS was investigated by dopamine and homovanillic acid ( HVA ) in the lumbar cerebrospinal fluid ( CSF ) of 17 patients before and after therapeutic rTMS for three or four months . rTMS was applied manually to the frontal areas 60 times per session , i. e. , 30 times per side using a large circular coil , a pulse intensity of 700 V , and a frequency of 0.2 Hz . Sessions were continued once a week for 2 months . The 9 control patients showed no changes of symptoms between the initial evaluation and that after 2 months of sham rTMS . In contrast , all 9 patients receiving rTMS showed a significant decrease of the modified H&Y and UPDRS scores after 2 months , while the Schwab and Engl and ADL Scale scores increased significantly . In the second CSF sample from patients receiving rTMS , HVA showed a significant decrease These results suggest that rTMS is beneficial for the symptoms of Parkinson 's disease and that it may act via inhibition of dopaminergic systems Cortical excitability of the primary motor cortex is altered in patients with Parkinson 's disease ( PD ) . Therefore , modulation of cortical excitability by high frequency repetitive transcranial magnetic stimulation ( rTMS ) of the motor cortex might result in beneficial effects on motor functions in PD . The present study aims to evaluate the effect of rTMS of the motor cortex on motor functions in patients with PD . Thirty-six unmedicated PD patients were included consecutively in this study . The patients were assigned in a r and omized pattern to one of two groups , one group receiving real-rTMS ( suprathreshold 5-Hz , 2000 pulses once a day for 10 consecutive days ) and the second group receiving sham-rTMS using closed envelopes . Total motor section of Unified Parkinson 's Disease Rating Scale ( UPDRS ) , walking speed , and self- assessment scale were performed for each patient before rTMS and after the first , fifth , 10th sessions , and then after 1 month . Evaluation of these measures was performed blindly without knowing the type of rTMS . anova for repeated measurements revealed a significant time effect for the total motor UPDRS , walking speed and self- assessment scale during the course of the study in the group of patients receiving real-rTMS ( P = 0.0001 , 0.001 , and 0.002 ) , while no significant changes were observed in the group receiving sham-rTMS except in self- assessment scale ( P = 0.019 ) . A 10-day course of real-rTMS result ed in statistically significant long-term improvement of the motor functions in comparison with the sham-rTMS . The rTMS could have a therapeutic role of for PD patients Ten unmedicated patients with Parkinson 's disease received sub-threshold 5-Hz repetitive transcranial magnetic stimulation ( rTMS ) over the primary motor h and area ( M1(H AND ) ) contralaterally to the more affected upper limb . Compared to a midfrontal sham-rTMS , real-rTMS over M1(H AND ) was associated with a significant decrease in the global motor UPDRS score 1 h after the cessation of rTMS . This was mainly due to a clinical improvement in the arm contralaterally to the stimulated M1(H AND ) . These preliminary data suggest that focal rTMS of M1(H AND ) may have a therapeutic potential in PD Repetitive transcranial magnetic stimulation ( rTMS ) can modulate cortical excitability and activation and consequently may affect clinical symptoms in neurological conditions characterized by altered motor cortex functions . There are conflicting reports whether low-frequency rTMS has any clinical effects in Parkinson 's disease ( PD ) . Ten patients with PD had rTMS ( 1800 stimuli at just below active motor threshold intensity ) at 1Hz rate delivered over the motor cortex for four consecutive days on two separate occasions . On one of these real rTMS was used and on the other sham rTMS ( placebo ) was used . Evaluations with UPDRS Part 3 ( Motor Scale ) were done in practically defined off-phase at the baseline and one day after the end of each of the treatment series . Neither total Motor Scale scores nor subscores for axial symptoms , rigidity , bradykinesia , and tremor showed any significant difference . The results do not confirm presence of residual beneficial clinical after-effects of consecutive daily applications of low-frequency rTMS on motor symptoms in PD , at least when 1800 stimuli at subthreshold intensity are applied for four days Previous studies in patients with Parkinson 's disease have reported that a single session of repetitive transcranial magnetic stimulation ( rTMS ) can improve some or all of the motor symptoms for 30 to 60 minutes . A recent study suggested that repeated sessions of rTMS lead to effects that can last for at least 1 month . Here we report data that both confirm and extend this work . Fifty-five unmedicated PD patients were classified into four groups : two groups ( early and late PD ) received 25 Hz rTMS bilaterally on the motor arm and leg areas ; other groups acted as control for frequency ( 10 Hz ) and for site of stimulation ( occipital stimulation ) . All patients received six consecutive daily sessions ( 3,000 pulses for each session ) . The first two groups then received a further three booster sessions ( 3 consecutive days of rTMS ) after 1 , 2 , and 3 months , while the third group had only one additional session after the first month . Unified Parkinson 's Disease Rating Scale ( UPDRS ) , walking time , key-tapping speed , and self- assessment scale were measured for each patient before and after each rTMS session and before and after the monthly sessions . Compared to occipital stimulation , 25 Hz rTMS over motor areas improved all measures in both early and late groups ; the group that received 10 Hz rTMS improved more than the occipital group but less than the 25 Hz groups . The effect built up gradually during the sessions and was maintained for 1 month after , with a slight reduction in efficacy . Interestingly , the effect was restored and maintained for the next month by the booster sessions . We conclude that 25 Hz rTMS can lead to cumulative and long-lasting effects on motor performance In a placebo-controlled , single-blinded , crossover study , we assessed the effect of " real " repetitive transcranial magnetic stimulation ( rTMS ) versus " sham " rTMS ( placebo ) on peak dose dyskinesias in patients with Parkinson 's disease ( PD ) . Ten patients with PD and prominent dyskinesias had rTMS ( 1,800 pulses ; 1 Hz rate ) delivered over the motor cortex for 4 consecutive days twice , once real stimuli and once sham stimulation were used ; evaluations were done at the baseline and 1 day after the end of each of the treatment series . Direct comparison between sham and real rTMS effects showed no significant difference in clinician-assessed dyskinesia severity . However , comparison with the baseline showed small but significant reduction in dyskinesia severity following real rTMS but not placebo . The major effect was on dystonia subscore . Similarly , in patient diaries , although both treatments caused reduction in subjective dyskinesia scores during the days of intervention , the effect was sustained for 3 days after the intervention for the real rTMS only . Following rTMS , no side effects and no adverse effects on motor function and PD symptoms were noted . The results suggest the existence of residual beneficial clinical aftereffects of consecutive daily applications of low-frequency rTMS on dyskinesias in PD . The effects may be further exploited for potential therapeutic uses |
737 | 26,358,158 | Given the number of MS relapses reported for the exercise condition ( N = 25 ) and non-exercise control condition ( N = 26 ) , exercise does not seem to be associated with a significant risk of a MS relapse .
However , in general , MS relapses were defined and reported poorly .
Exercise therapy can be prescribed in people with MS without harm .
Exercise therapy , and particularly endurance , mixed , or ' other ' training , may reduce self reported fatigue . | BACKGROUND Multiple sclerosis ( MS ) is an immune-mediated disease of the central nervous system affecting an estimated 1.3 million people worldwide .
It is characterised by a variety of disabling symptoms of which excessive fatigue is the most frequent .
Fatigue is often reported as the most invalidating symptom in people with MS .
Various mechanisms directly and indirectly related to the disease and physical inactivity have been proposed to contribute to the degree of fatigue .
Exercise therapy can induce physiological and psychological changes that may counter these mechanisms and reduce fatigue in MS .
OBJECTIVES To determine the effectiveness and safety of exercise therapy compared to a no-exercise control condition or another intervention on fatigue , measured with self-reported question naires , of people with MS . | OBJECTIVE To investigate the acute effects of long-term whole-body vibration on leg muscle performance and functional capacity in persons with multiple sclerosis . DESIGN A r and omized controlled trial . SUBJECTS Twenty-five patients with multiple sclerosis ( mean age 47.9 ± 1.9 years ; Exp and ed Disability Status Scale 4.3 ± 0.2 ) were assigned r and omly to whole-body vibration training ( n = 11 ) or to a control group ( n = 14 ) . METHODS The whole-body vibration group performed static and dynamic leg squats and lunges on a vibration platform ( 25 - 45 Hz , 2.5 mm amplitude ) during a 20-week training period ( 5 training sessions per 2-week cycle ) , and the control group maintained their usual lifestyle . PRE- , MID- ( 10 weeks ) and POST- ( 20 weeks ) knee-muscle maximal isometric and dynamic strength , strength endurance and speed of movement were measured using isokinetic dynamometry . Function was determined through the Berg Balance Scale , Timed Up and Go , Two-minute Walk Test and the Timed 25-Foot Walk Test . RESULTS Leg muscle performance and functional capacity were not altered following 10 or 20 weeks of whole-body vibration . CONCLUSION Under the conditions of the present study , the applied 20-week whole-body vibration exercise protocol did not improve leg muscle performance or functional capacity in mild- to moderately impaired persons with multiple sclerosis during and immediately after the training programme BACKGROUND Balance disorders are common in multiple sclerosis . AIM Aim of the study is to investigate the effectiveness of an Internet-based home training program ( e-Training ) to improve balance in patients with multiple sclerosis . DESIGN A r and omized , controlled study . SETTING Academic teaching hospital in cooperation with the therapeutic riding center Gut Üttingshof , Bad Mergentheim . POPULATION Eighteen multiple sclerosis patients ( mean EDSS 3,5 ) took part in the trial . Outcome of patients using e-Training ( N.=9 ) was compared to the outcome of patients receiving hippotherapy ( N.=9 ) , which can be considered as an advanced concept for the improvement of balance and postural control in multiple sclerosis . METHODS After simple r and om allocation patients received hippotherapy or Internet-based home training ( balance , postural control and strength training ) twice a week for 12 weeks . Assessment s were done before and after the intervention and included static and dynamic balance ( primary outcome ) . Isometric muscle strength of the knee and trunk extension/flexion ( dynamometer ) , walking capacity , fatigue and quality of life served as secondary outcome parameters . RESULTS Both intervention groups showed comparable and highly significant improvement in static and dynamic balance capacity , no difference was seen between the both intervention groups . However looking at fatigue and quality of life only the group receiving hippotherapy improved significantly . CONCLUSION Since e-Training shows even comparable effects to hippotherapy to improve balance , we believe that the established Internet-based home training program , specialized on balance and postural control training , is feasible for a balance and strength training in persons with multiple sclerosis . CLINICAL REHABILITATION IMPACT We demonstrated that Internet-based home training is possible in patients with multiple sclerosis Background Patients suffering from Multiple Sclerosis ( MS ) experience a wide array of symptoms , including balance problems , mobility impairment , fatigue and depression . Physical exercise has recently been acknowledged as a treatment option complementary to medication . However , information regarding putative effects of structured exercise programs on neurological symptoms is sparse . Tai Chi , a Chinese martial art incorporating physical exercise and mindfulness training , has been shown to yield health benefits in various neurological groups . It seems particularly suitable for patients with motoric deficits as it challenges coordination and balance . The purpose of the current study was to explore the therapeutic value of structured Tai Chi training for coordination , balance , fatigue and depression in mildly disabled MS patients . Methods A sample of 32 MS patients ( Exp and ed Disability Status Scale , EDSS < 5 ) was examined . A structured Tai Chi course was devised and a Tai Chi group participated in two weekly sessions of 90 minutes duration for six months , while a comparison group received treatment as usual ( TAU ) . Both groups were examined prior to and following the six-months interval with regards to balance and coordination performance as well as measures of fatigue , depression and life satisfaction . Results Following the intervention , the Tai Chi group showed significant , consistent improvements in balance , coordination , and depression , relative to the TAU group ( range of effect-sizes : partial η2 = 0.16 – 0.20 ) . Additionally , life satisfaction improved ( partial η2 = 0.31 ) . Fatigue deteriorated in the comparison group , whereas it remained relatively stable in the Tai Chi group ( partial η2 = 0.24 ) . Conclusions The consistent pattern of results confirms that Tai Chi holds therapeutic potential for MS patients . Further research is needed to determine underlying working mechanisms , and to verify the results in a larger sample and different MS subgroups Background Multiple Sclerosis ( MS ) is a disease of the central nervous system that results in many symptoms including mobility limitation and fatigue . Patients and Methods Thirty-one MS patients , all female with mean of age of 36.75 years and Exp and ed Disability Status Scale scores ( EDSS ) of 1.0 to 4.0 were recruited . Subjects were r and omly assigned to one of the three groups : treadmill training , yoga or control groups . Treadmill training and yoga practice consisted of 8 weeks ( 24 sessions , thrice weekly ) . The control group followed their own routine treatment program . Balance , speed and endurance of walking , fatigue , depression and anxiety were measured by Berg Balance scores , time for 10 m walk and distance for a two minute walk , Fatigue Severity Scale ( FFS ) , Beck Depression Inventory ( BDI ) and Beck Anxiety Inventory ( BAI ) , respectively . Results Comparison of results have shown that pre- and post- interventions produced significant improvements in the balance score , walking endurance , FFS score , BDI score and BAI score in the treadmill training group and yoga group . However , 10 m walk time decreased in the treadmill training group but did not show any clear change in the yoga group . Moreover , the analysis showed significant differences between the treadmill training group and yoga group for BAI score . Conclusions These results suggest that treadmill training and yoga practice improved ambulatory function , fatigue and mood status in the individuals with mild to moderate MS Objective : The primary aim was to investigate the comparative effects of massage therapy and exercise therapy on patients with multiple sclerosis . The secondary aim was to investigate whether combination of both massage and exercise has an additive effect . Design : R and omized controlled pilot trial with repeated measurements and blinded assessment s. Setting : Local Multiple Sclerosis Society . Subjects : A total of 48 patients with multiple sclerosis were r and omly assigned to four equal subgroups labelled as massage therapy , exercise therapy , combined massage – exercise therapy and control group . Interventions : The treatment group received 15 sessions of supervised intervention for five weeks . The massage therapy group received a st and ard Swedish massage . The exercise therapy group was given a combined set of strength , stretch , endurance and balance exercises . Patients in the massage – exercise therapy received a combined set of massage and exercise treatments . Patients in the control group were asked to continue their st and ard medical care . Main measures : Pain , fatigue , spasticity , balance , gait and quality of life were assessed before and after intervention . Results : Massage therapy result ed in significantly larger improvement in pain reduction ( mean change 2.75 points , P = 0.001 ) , dynamic balance ( mean change , 3.69 seconds , P = 0.009 ) and walking speed ( mean change , 7.84 seconds , P = 0.007 ) than exercise therapy . Patients involved in the combined massage – exercise therapy showed significantly larger improvement in pain reduction than those in the exercise therapy ( mean change , 1.67 points , P = 0.001 ) . Conclusions : Massage therapy could be more effective than exercise therapy . Moreover , the combination of massage and exercise therapy may be a little more effective than exercise therapy alone Background : Resistance training studies in multiple sclerosis ( MS ) often use short intervention periods . Furthermore , training efficiency could be optimized by unilateral training and /or electrical stimulation . Objective : To examine the effect(s ) of unilateral long-term ( 20 weeks ) st and ardized resistance training with and without simultaneous electro-stimulation on leg muscle strength and overall functional mobility . Methods : A r and omized controlled trial involving 36 persons with MS . At baseline ( PRE ) and after 10 ( MID ) and 20 ( POST ) weeks of st and ardized ( ACSM ) light to moderately intense unilateral leg resistance training ( RESO , n = 11 ) only or resistance training with simultaneous electro-stimulation ( RESE , n = 11 , 100 Hz , biphasic symmetrical wave , 400 µs ) , maximal isometric strength of the knee extensors and flexors ( 45 ° , 90 ° knee angle ) and dynamic ( 60–180 ° /s ) knee-extensor strength was measured and compared with a control group ( CON , n = 14 ) . Functional mobility was evaluated using the Timed Get Up and Go , Timed 25 Foot Walk , Two-Minute Walk Test , Functional Reach and Rivermead Mobility Index . Results : Maximal isometric knee extensor ( 90 ° , MID : + 10 ± 3 % , POST : + 10 ± 4 % ) in RESO and knee flexor ( 45 ° , POST : + 7 ± 4 % ; 90 ° , POST : + 9 ± 5 % ) in RESE strength increased ( p < 0.05 ) compared with CON but RESO and RESE did not differ . Also , impaired legs responded positively to resistance training ( unilateral leg strength analysis ) and functional reaching increased significantly in RESO ( + 18 % ) compared with CON . Dynamic muscle strength and the remaining functional mobility tests did not change . Conclusion : Long-term light to moderately intense resistance training improves muscle strength in persons with MS but simultaneous electro-stimulation does not further improve training outcome BACKGROUND People with Multiple Sclerosis ( PwMS ) are less physically active than the general population and pragmatic approaches design ed to equip them with the skills and confidence to participate in long-term physical activity are required . OBJECTIVE The objective of this study was to determine the feasibility of a pragmatic exercise intervention in PwMS . METHODS A voluntary sample of 30 PwMS ( male n = 4 , female n = 26 ; mean age = 40 years ; range = 24 - 49 years ) , with mild to moderate disability ( EDSS ≤ 5.5 ) , were recruited from eligible participants attending outpatient clinics . A total of 28 participants were r and omised to a 10 week pragmatic exercise intervention ( 2 × supervised and 1 × home-based session per week ) or usual care . Clinical , functional and quality of life ( MSQoL-54 ) outcomes were assessed at baseline , immediately and 3 months after the intervention . RESULTS Attrition was low ( 2 participants lost to immediate follow-up and 4 participants lost to 3 month follow-up ) , with high compliance rates ( > 75 % of all sessions ) . The intervention group achieved progression of exercise volume ( 24.3 ± 7.0 to 30.9 ± 5.5 min per session ) , intensity ( 60.4 ± 8.8 to 67.7 ± 6.9 % HR max ) and training impulse ( min × average HR = training impulse/load [ arbitrary units ; AU ] ) ( 2600 ± 1105 to 3210 ± 1269AU ) during the intervention , whilst significantly increasing(P = 0.050 ) their physical composite score ( MSQOL-54 ) at 10 weeks and readiness to exercise ( P = 0.003 ) at 3 months compared with usual care . CONCLUSION This pragmatic intervention was feasible for PwMS , but further research is needed to assess its long-term impact on physical activity behaviour Background : Extensive research on both healthy subjects and patients with central nervous damage has eluci date d a crucial role of postural adjustment reactions and central sensory integration processes in generating and “ shaping ” locomotor function , respectively . Whether robotic-assisted gait devices might improve these functions in Multiple sclerosis ( MS ) patients is not fully investigated in literature . Purpose : The aim of this study was to compare the effectiveness of end-effector robot-assisted gait training ( RAGT ) and sensory integration balance training ( SIBT ) in improving walking and balance performance in patients with MS . Methods : Twenty-two patients with MS ( EDSS : 1.5–6.5 ) were r and omly assigned to two groups . The RAGT group ( n = 12 ) underwent end-effector system training . The SIBT group ( n = 10 ) underwent specific balance exercises . Each patient received twelve 50-min treatment sessions ( 2 days/week ) . A blinded rater evaluated patients before and after treatment as well as 1 month post treatment . Primary outcomes were walking speed and Berg Balance Scale . Secondary outcomes were the Activities-specific Balance Confidence Scale , Sensory Organization Balance Test , Stabilometric Assessment , Fatigue Severity Scale , cadence , step length , single and double support time , Multiple Sclerosis Quality of Life-54 . Results : Between groups comparisons showed no significant differences on primary and secondary outcome measures over time . Within group comparisons showed significant improvements in both groups on the Berg Balance Scale ( P = 0.001 ) . Changes approaching significance were found on gait speed ( P = 0.07 ) only in the RAGT group . Significant changes in balance task-related domains during st and ing and walking conditions were found in the SIBT group . Conclusion : Balance disorders in patients with MS may be ameliorated by RAGT and by SIBT This is a r and omised control study , to determine the effect of aerobic and strength exercise on physical fitness and quality of life in patients with mild multiple sclerosis ( MS ) . Sixteen out patients with definitive MS , aged 18 - 50 , with an Exp and ed Disability Status Scale ( EDSS ) < 4 , completed the study . Every patient was evaluated according to physical fitness with peak oxygen consumption ( V'O2peak ) , workload and anaerobic threshold ; quality of life ( SF-36 ) ; and degree of disability ( EDSS ) . The patients were then r and omised to an exercise group ( EG ) ( n = 6 ) or a control group ( CG ) ( n = 10 ) . The EG exercised three times a week for five weeks , and the CG did not change their habits regarding exercise . In the EG , the mean change in workload was 0.34 W/kg ( 95 % confidence interval ( CI ) : 0.09 - 0.58 ) , the mean change in V'O2peak was 4.54 mL/kg per minute ( 95 % CI : 1.65 - 7.44 ) , and the mean change in anaerobic threshold was 0.32 L/min ( 95 % CI : 0.08 - 0.57 ) . There was a tendency towards improved quality of life , and no change was detected in the degree of disability . This study confirms that brief , moderate , aerobic exercise improves physical fitness in individuals with mild MS . No evidence was found for worsening of MS symptoms in association with exercises . Multiple Sclerosis 2007 ; 13 : 776 - 782 . Background and Purpose — Fatigue is a common , persistent consequence of stroke , and no evidence -based treatments are currently available to alleviate fatigue . A new treatment combining cognitive therapy ( CO ) with grade d activity training ( GRAT ) , called COGRAT , was developed to alleviate fatigue and fatigue-related symptoms . This study compared the effectiveness of the COGRAT intervention with a CO-only intervention after a 3-month qualification period without intervention . Methods — This r and omized , controlled , assessor-blind clinical trial was conducted in 8 rehabilitation centers . Eighty-three stroke patients ( > 4 months after stroke ) were r and omly assigned to 12 weeks of CO or COGRAT after qualification . Seventy-three patients completed treatment and 68 were available at follow-up . Primary outcomes ( Checklist Individual Strength – subscale Fatigue ( CIS-f ) ; self-observation list – fatigue ( SOL-f ) ) and secondary outcomes ( Hospital Anxiety and Depression Scale , Stroke-Adapted Sickness Impact Profile , SOL-pain , SOL-sleep-D , 6-minute walk test ) were collected at baseline ( before and after qualification period ) and after treatment ( immediate and 6-month follow-up ) . Results — The qualification period showed stable outcome measures . Both treatments showed significant beneficial effects on fatigue ( CIS-f : & eegr;p2=0.48 , P<0.001 ) and other outcomes ( except pain and anxiety ) with intention-to-treat analyses . Gains for the COGRAT group exceeded those in the CO group on number of individuals showing clinical improvement on the CIS-f ( ≥8 points : 58 % versus 24 % ) and on physical endurance ( & eegr;p2=0.20 , P<0.001 ) . Conclusions — A 12-week cognitive therapy program can alleviate persistent fatigue after stroke . The best results are obtained when cognitive therapy is augmented with grade d activity training . Clinical Trial Registration — URL : http://www.trialregister.nl . Unique identifier : NTR2704 Background Functional electrical stimulation ( FES ) , is a means of producing a contraction in a paralyzed or weak muscle to enable function through electrical excitation of the innervating nerve . Objective This two-group r and omized trial assessed the effects of single channel common peroneal nerve stimulation on objective aspects of gait relative to exercise therapy for people with secondary progressive multiple sclerosis ( SPMS ) . Methods Forty-four people with a diagnosis of SPMS and unilateral dropped foot completed the trial . Twenty patients were r and omly allocated to a group receiving FES and the remaining 24 to a group receiving a physiotherapy home exercise program for a period of 18 weeks . Results The exercise group showed a statistically significant increase in 10 m walking speed and distance walked in 3 min , relative to the FES group who showed no significant change in walking performance without stimulation . At each stage of the trial , the FES group performed to a significantly higher level with FES than without for the same outcome measures . Conclusion Exercise may provide a greater training effect on walking speed and endurance than FES for people with SPMS . FES may provide an orthotic benefit when outcome is measured using the same parameters . More research is required to investigate the combined therapeutic effects of FES and exercise for this patient group Background and Purpose : Resistance exercise via negative , eccentrically induced work ( RENEW ) has been shown to be associated with improvements in strength , mobility , and balance in multiple clinical population s. However , RENEW has not been reported for individuals with multiple sclerosis ( MS ) . Methods : Nineteen individuals with MS ( 8 men , 11 women ; age mean = 49 ± 11 years ; Exp and ed Disability Status Scale [ EDSS ] mean = 5.2 ± 0.9 ) were r and omized into either st and ard exercise ( ST AND ) or st and ard exercise and RENEW training ( RENEW ) for 3 × /week for 12 weeks . Outcome measures were lower extremity strength ( hip/knee flexion and extension , ankle plantar and dorsiflexion , and the sum of these individual values [ sum strength ] ) ; Timed Up and Go ( TUG ) , 10-m walk , self-selected pace ( TMWSS ) and maximal-pace ( TMWMP ) , stair ascent ( S-A ) and descent ( S-D ) and 6-Minute Walk Test ( 6MWT ) , Berg Balance Scale ( BBS ) , Fatigue Severity Scale ( FSS ) . Results : No significant time effects or interactions were observed for strength , TUG , TMWSS , TMWMP , or 6MWT . However , the mean difference in sum strength in the RENEW group was 38.60 ( representing a 15 % increase ) compared to the sum strength observed in the ST AND group with a mean difference of 5.58 ( a 2 % increase ) . A significant interaction was observed for S-A , S-D , and BBS as the ST AND group improved whereas the RENEW group did not improve in these measures . Discussion and Conclusions : Contrary to results in other population s , the addition of eccentric training to st and ard exercises did not result in significantly greater lower extremity strength gains in this group of individuals with MS . Further this training was not as effective as st and ard exercise alone in improving balance or the ability to ascend and descend stairs . Following data collection , re assessment of required sample size indicates we were likely underpowered to detect strength differences between groups Objective : Health-related quality of life ( HRQOL ) is often much reduced among individuals with multiple sclerosis ( MS ) , and incidences of depression , fatigue , and anxiety are high . We examined effects of a mindfulness-based intervention ( MBI ) compared to usual care ( UC ) upon HRQOL , depression , and fatigue among adults with relapsing-remitting or secondary progressive MS . Methods : A total of 150 patients were r and omly assigned to the intervention ( n = 76 ) or to UC ( n = 74 ) . MBI consisted of a structured 8-week program of mindfulness training . Assessment s were made at baseline , postintervention , and 6 months follow-up . Primary outcomes included disease-specific and disease-aspecific HRQOL , depression , and fatigue . Anxiety , personal goal attainment , and adherence to homework were secondary outcomes . Results : Attrition was low in the intervention group ( 5 % ) and attendance rate high ( 92 % ) . Employing intention-to-treat analysis , MBI , compared with UC , improved nonphysical dimensions of primary outcomes at postintervention and follow-up ( p < 0.002 ) ; effect sizes , 0.4–0.9 posttreatment and 0.3–0.5 at follow-up . When analyses were repeated among subgroups with clinical ly relevant levels of preintervention depression , fatigue , or anxiety , postintervention and follow-up effects remained significant and effect sizes were larger than for the total sample . Conclusions : In addition to evidence of improved HRQOL and well-being , these findings demonstrate broad feasibility and acceptance of , as well as satisfaction and adherence with , a program of mindfulness training for patients with MS . The results may also have treatment implication s for other chronic disorders that diminish HRQOL . Classification of evidence : This trial provides Class III evidence that MBI compared with UC improved HRQOL , fatigue , and depression up to 6 months postintervention Background : The use of interactive video games is exp and ing within rehabilitation . The evidence base is , however , limited . Objective : Our aim was to evaluate the effects of a Nintendo Wii Fit ® balance exercise programme on balance function and walking ability in people with multiple sclerosis ( MS ) . Methods : A multi-centre , r and omised , controlled single-blinded trial with r and om allocation to exercise or no exercise . The exercise group participated in a programme of 12 supervised 30-min sessions of balance exercises using Wii games , twice a week for 6–7 weeks . Primary outcome was the Timed Up and Go test ( TUG ) . In total , 84 participants were enrolled ; four were lost to follow-up . Results : After the intervention , there were no statistically significant differences between groups but effect sizes for the TUG , TUGcognitive and , the Dynamic Gait Index ( DGI ) were moderate and small for all other measures . Statistically significant improvements within the exercise group were present for all measures ( large to moderate effect sizes ) except in walking speed and balance confidence . The non-exercise group showed statistically significant improvements for the Four Square Step Test and the DGI . Conclusion : In comparison with no intervention , a programme of supervised balance exercise using Nintendo Wii Fit ® did not render statistically significant differences , but presented moderate effect sizes for several measures of balance performance Background : Exercise programmes that can demonstrate evidence of long-lasting clinical effectiveness are needed for people with multiple sclerosis ( PwMS ) . Objective : The objective of this study was to assess the effects of a practically implemented exercise programme on self-directed exercise behaviour and important health outcomes in PwMS to nine months of follow-up . Methods : We conducted a parallel-arm , r and omised controlled trial : 120 PwMS ( Exp and ed Disability Status Scale ( EDSS ) 1.0–6.5 ) r and omised to a three-month exercise intervention plus usual care , or usual care only . Two supervised plus one home-exercise session ( weeks 1–6 ) were followed by one supervised and two home-exercise sessions ( weeks 7–12 ) . Cognitive-behavioural techniques promoted long-term exercise behaviour change . Outcomes were blindly assessed at baseline and at three and nine months after r and omisation . The primary outcome was self-reported exercise behaviour ( Godin Leisure Time Exercise Question naire ( GLTEQ ) ) . Secondary outcomes included fatigue and health-related quality of life ( HRQoL ) . Results : The intervention increased self-reported exercise ( 9.6 points ; 95 % CI : 2.0 to 17.3 points ; p = 0.01 ) and improved fatigue ( p < 0.0001 ) and many HRQoL domains ( p ≤ 0.03 ) at three months . The improvements in emotional well-being ( p = 0.01 ) , social function ( p = 0.004 ) and overall quality of life ( p = 0.001 ) were sustained for nine months . Conclusion : This pragmatic approach to implementing exercise increases self-reported exercise behaviour , improves fatigue and leads to a sustained enhancement of HRQoL domains in PwMS Çakıt BD , Nacir B , Genç H , Saraçoğlu M , Karagöz A , Erdem HR , Ergün U : Cycling progressive resistance training for people with multiple sclerosis : A r and omized controlled study . Objective : To evaluate the effects of cycling progressive resistance training combined with balance exercises on walking speed , balance , fatigue , fear of falling , depression , and quality of life in patients with multiple sclerosis . Design : In this prospect i ve r and omized controlled trial , 45 patients were r and omized into two exercise training ( n = 30 ) groups and one control ( n = 15 ) group . The patients in training group 1 ( n = 15 ) underwent progressive resistance training on a bicycle ergometer and balance exercise , whereas group 2 ( n = 15 ) patients received a home-based lower-limb strengthening and balance exercise . Outcome measures , including the duration of exercise , tolerated maximum workload , timed up and go test , Dynamic Gait Index , functional reach , Falls Efficacy scale , 10-m walk test , Fatigue Severity Scale , Beck Depression Inventory , and Short Form 36 scores , were assessed initially and at 8 wks . Results : After dropouts , the whole study group consisted of 20 women and 13 men ( mean age , 37.9 ± 10.43 yrs ) . In training group 1 , duration of exercise , tolerated maximum workload , timed up and go test , Dynamic Gait Index , functional reach , falls efficacy scale , 10-m walk test , Fatigue Severity scale , and Beck Depression Inventory scores , and in group 2 , the mean duration of exercise , tolerated maximum workload , and Falls Efficacy scale scores were significantly improved after the training program ( P < 0.05 ) . There were no significant improvements in any of the outcome measurements in the control group ( P > 0.05 ) . In between-group comparisons , improvements in outcome measures of group 1 patients were significantly higher than those in other groups , except for 10-m walking test . Group 1 patients showed statistically significant improvement in physical functioning and role-physical functioning scales of the Short Form 36 ( P < 0.01 and P < 0.05 , respectively ) , and group 2 patients showed statistically significant improvement in only physical functioning scale of Short Form 36 ( P < 0.05 ) after 8 wks . Conclusions : Specific exercise programs , including cycling progressive resistance training , may improve balance , fatigue , and depression and reduce fear of falling in patients with multiple sclerosis without worsening multiple sclerosis signs and symptoms Objective : To investigate the effects of aerobic and strength exercise on motor fatigue of knee flexor and extensor muscles in subjects with multiple sclerosis ( MS ) . Design : A r and omized controlled trial . Setting : At Masku Neurological Rehabilitation Centre , Masku , and the Social Insurance Institution , Research Department , Turku , Finl and . Subjects : Ninety-five MS patients with mild to moderate disability were r and omized into exercise group ( n = 47 ) and a control group ( n = 48 ) . Intervention : Participants in the exercise group attended in a supervised exercise period of three weeks , which was followed by a home exercise programme lasting for 23 weeks . Patients in the control group continued with their normal living . Outcome measures : Motor fatigue of knee flexor and extensor muscles was measured during a static 30-s maximal sustained muscle contraction . The decline in force ( Nm ) during the 30 s was recorded , and a fatigue index ( FI ) was calculated . Subjective fatigue was measured by using the Fatigue Severity Scale ( FSS ) . The Ambulatory Fatigue Index ( AFI ) was calculated on the basis of a 500-m walking test . Assessment took place at baseline , at the third week ( not for the control group ) and at the 26th week . All outcome variables were analysed , men and women together , and some interesting contrasts were analysed by gender . Results : Associations were observed with changes in extension FI and Exp and ed Disability Status Scale ( EDSS ) score and mean extension torque ( Nm ) , but not with changes in FI and aerobic or strength exercise activity , mean AFI , mean FSS or in mean knee flexion torque . AFI was decreased in all subject groups ( p = 0.007 ) . Motor fatigue was reduced in knee flexion ( p = 0.0014 ) and extension ( ns ) among female but not in male exercisers after six months of exercise . The exercise activity of women was 25 % higher than that of the men . Conclusions : Six months of exercise reduced motor fatigue in women , but not in men OBJECTIVE To examine the effectiveness of aquatic exercise training on fatigue and health-related quality of life ( HRQOL ) in women with multiple sclerosis ( MS ) . DESIGN R and omized controlled trial , 4-week and 8-week follow-up . SETTING Referral center of a multiple sclerosis society . PARTICIPANTS Women ( N=32 ) diagnosed with relapsing-remitting MS ( mean age ± SD , 32.6±8.0y ) were recruited into this study . After undergoing baseline testing by a neurologist , participants were r and omly assigned to either an intervention ( aquatic exercise ) or a control group . INTERVENTIONS The intervention consisted of 8 weeks supervised aquatic exercise in a swimming pool ( 3 times a week , each session lasting 60min ) . MAIN OUTCOME MEASURES At baseline , 4 weeks , and 8 weeks , fatigue and HRQOL were assessed by a blind assessor using the Modified Fatigue Impact Scale and the Multiple Sclerosis Quality of Life-54 question naire , respectively . A mixed-model approach to repeated- measures analysis of variance was used to detect within- and between-subject effects . RESULTS Findings are based on 21 patients ( 10 from the exercise group and 11 from the control group ) who had data available on outcomes . There was no significant difference between the 2 groups at the baseline . Patients in the aquatic exercise group showed significant improvements in fatigue and subscores of HRQOL after 4 and 8 weeks compared with the control group . Results obtained from the intention-to-treat analysis were consistent with those of per- protocol analysis . CONCLUSIONS The findings suggest that aquatic exercise training can effectively improve fatigue and HRQOL of patients with MS and should be considered in the management of this relatively common public health problem Objective : To investigate the effect of an eight-week home-based physiotherapy programme in reducing physical impairment , disability and psychological distress for people with moderate to severe multiple sclerosis ( MS ) . Design : Pilot r and omized controlled trial . Setting : Community ; subjects ’ homes . Subjects : Thirty people moderately to severely affected by MS ( Extended Disability Status Score , EDSS , 6.5–8 ) were r and omized to an intervention or control group . Intervention : The intervention group received twice weekly , home-based physiotherapy for eight weeks and the control group received usual care . Main measures : The following outcome measures were recorded at baseline , post-intervention ( Week 8) and at follow-up ( Week 16 ) . Primary outcome measure ; Multiple Sclerosis Impact Scale ( MSIS29 ) and secondary outcome measures assessed physical impairment , MS symptoms , quality of life , mood , and disability . Results : Although the Group * Time interaction failed to reach statistical significance with MSIS29 ( p = 0.925 ) , MS – related symptom checklist ( MS-RS ) ( p = 0.627 ) and for lower limb strength , right knee extension ( p = 0.375 ) and right knee flexion ( p = 0.794 ) , there is more evidence of altered levels in the treatment group than in the control group . Conclusion : A minimum of 58 subjects per group are required to achieve a power of 80 % at the 5 % level of significance based on the MSIS29 . A larger scale study is required Objectives – Effects of endurance training in multiple sclerosis ( MS ) patients complaining of motor fatigue Background . Mobility limitations are a key feature of MS and 25 % will require the use of a walking aid 15 years after diagnosis . Few studies have specifically evaluated the effectiveness of physiotherapy and exercise interventions delivered in the community for those with significant disability . Methods . An assessor blind , block r and omised , and controlled study recruited participants who required bilateral assistance for gait and who occasionally used wheelchairs for longer distances . They were r and omised to 10 weeks of group physiotherapy ( balance and strengthening exercises ) , individual physiotherapy , yoga group , or a control group . Results . Repeated measures ANOVA found significant time effects for physical component of MSIS-29v2 ( f = 7.993 , P = 0.006 ) and MFIS ( f = 8.695 , P = 0.004 ) . The group × time interaction was significant for the BBS ( f = 4.391 , P = 0.006 ) . Post hoc analysis revealed no difference between group and individual physiotherapy for BBS . There was no significant difference between groups but the 6MWT improved for individual physiotherapy ( P = 0.001 ) and MSIS-29v2 psychological score for group physiotherapy ( P = 0.005 ) . Discussion . This study found that balance and strengthening exercises , delivered in the community to those with significant mobility limitations , improve balance . The effect on walking endurance and patient-reported outcomes are unclear and warrants further investigation with a larger control group with similar baseline characteristics to the intervention groups Objective : To determine the effect of yoga and of aerobic exercise on cognitive function , fatigue , mood , and quality of life in multiple sclerosis ( MS ) . Methods : Subjects with clinical ly definite MS and Exp and ed Disability Status Score less than or equal to 6.0 were r and omly assigned to one of three groups lasting 6 months : weekly Iyengar yoga class along with home practice , weekly exercise class using a stationary bicycle along with home exercise , or a waiting-list control group . Outcome assessment s performed at baseline and at the end of the 6-month period included a battery of cognitive measures focused on attention , physiologic measures of alertness , Profile of Mood States , State-Trait Anxiety Inventory , Multi-Dimensional Fatigue Inventory ( MFI ) , and Short Form (SF)-36 health-related quality of life . Results : Sixty-nine subjects were recruited and r and omized . Twelve subjects did not finish the 6-month intervention . There were no adverse events related to the intervention . There were no effects from either of the active interventions on either of the primary outcome measures of attention or alertness . Both active interventions produced improvement in secondary measures of fatigue compared to the control group : Energy and Fatigue ( Vitality ) on the SF-36 and general fatigue on the MFI . There were no clear changes in mood related to yoga or exercise . Conclusion : Subjects with MS participating in either a 6-month yoga class or exercise class showed significant improvement in measures of fatigue compared to a waiting-list control group . There was no relative improvement of cognitive function in either of the intervention groups Background : The influences of exercising on cytokine response , fatigue and cardiorespiratory values are important aspects of rehabilitation in persons with multiple sclerosis ( PwMS ) . Exercise performed within these programs is often practised in water but the effects of immersion on PwMS have not been systematic ally investigated . Objective : The objective of this study is to determine differences in cytokine and neurotrophin concentrations , fatigue and cardiorespiratory values in response to 3 week endurance training conducted on a cycle ergometer or an aquatic bike . Methods : A r and omized controlled clinical trial was conducted in 60 MS patients ( Exp and ed Disability Status Scale range 1.0–6.5 ) . Resting serum levels of brain-derived neurotrophic factor ( BDNF ) , nerve growth factor ( NGF ) , Interleukin-6 , soluble receptor of IL-6 and tumor necrosis factor alpha , and concentrations in response to cardiopulmonary exercise test ( CPET ) , fatigue and cardiorespiratory values were determined at entry and discharge . Subjects performed daily 30 minute training at 60 % of VO2max . Results : Cytokines and neurotrophins showed no significant differences between groups over the training intervention . Within the water group BDNF resting and post-CPET concentrations ( p<0.05 ) showed a significant increase and NGF tended to increase after the training intervention . Short-term effects on BDNF ( CEPT ) tended to increase at the start and significantly thereafter ( p<0.05 ) . No changes occurred in the l and group . Other cytokines and fatigue scores remained unchanged over the training period . Cardiorespiratory values improved significantly over time within both groups . Conclusion : This study indicates that aquatic training activates BDNF regulation and can be an effective training method during rehabilitation in PwMS OBJECTIVE The aim of this r and omized controlled trial was to test the hypothesis that a three-week whole body vibration ( WBV ) training in addition to a st and ard rehabilitation program improves walking ability in patients with Multiple Sclerosis ( MS ) . PATIENTS AND METHOD Sixty patients with definite MS were r and omly allocated to the intervention or control group . Training sessions were performed three times per week for three weeks . Patients adopted a moderate squat position on a vibration platform . The training sessions comprised series of 3 × 60-sec exercise sets with increasing amplitude between sessions from 1 to 2 mm . During the exercise series , the vibration platform was turned on for the intervention group and switched off for the control group . A mixed factor ANOVA was used to compare sit to st and test , timed up and go test , 10-meter walk test , and 6-min walk test data between patient groups and between baseline and follow-up . RESULTS All outcome measures improved from baseline to follow-up ( P < 0.001 ) . The 6-minute walk test showed significantly greater improvements from baseline to follow-up for the intervention than for the control group ( P < 0.001 ) . CONCLUSION Determinants of walking ability in patients with MS that are specific to walking endurance tasks are most affected by vibration training design ed to improve strength endurance Objective : To explore the effectiveness and participant experience of web-based physiotherapy for people moderately affected with Multiple Sclerosis ( MS ) and to provide data to establish the sample size required for a fully powered , definitive r and omized controlled study . Design : A r and omized controlled pilot study . Setting : Rehabilitation centre and participants ’ homes . Subjects : Thirty community dwelling adults moderately affected by MS ( Exp and ed Disability Status Scale 5 - 6.5 ) . Interventions : Twelve weeks of individualised web-based physiotherapy completed twice per week or usual care ( control ) . Online exercise diaries were monitored ; participants were telephoned weekly by the physiotherapist and exercise programmes altered remotely by the physiotherapist as required . Main measures : The following outcomes were completed at baseline and after 12 weeks ; 25 Foot Walk , Berg Balance Scale , Timed Up and Go , Multiple Sclerosis Impact Scale , Leeds MS Quality of Life Scale , MS-Related Symptom Checklist and Hospital Anxiety and Depression Scale . The intervention group also completed a website evaluation question naire and interviews . Results : Participants reported that website was easy to use , convenient , and motivating and would be happy to use in the future . There was no statistically significant difference in the primary outcome measure , the timed 25 ft walk in the intervention group ( P=0.170 ) , or other secondary outcome measures , except the Multiple Sclerosis Impact Scale ( P=0.048 ) . Effect sizes were generally small to moderate . Conclusion : People with MS were very positive about web-based physiotherapy . The results suggested that 80 participants , 40 in each group , would be sufficient for a fully powered , definitive r and omized controlled trial Background Fatigue and impaired upright postural control ( balance ) are the 2 most common findings in people with multiple sclerosis ( MS ) , with treatment approaches varying greatly in effectiveness . Objectives The aim of this study was to investigate the benefits of implementing a vestibular rehabilitation program for the purpose of decreasing fatigue and improving balance in patients with MS . Design The study was a 14-week , single-blinded , stratified blocked r and omized controlled trial . Setting Measurements were conducted in an outpatient clinical setting , and interventions were performed in a human performance laboratory . Patients Thirty-eight patients with MS were r and omly assigned to an experimental group , an exercise control group , or a wait-listed control group . Intervention The experimental group underwent vestibular rehabilitation , the exercise control group underwent bicycle endurance and stretching exercises , and the wait-listed control group received usual medical care . Measurements Primary measures were a measure of fatigue ( Modified Fatigue Impact Scale ) , a measure of balance ( posturography ) , and a measure of walking ( Six-Minute Walk Test ) . Secondary measures were a measure of disability due to dizziness or disequilibrium ( Dizziness H and icap Inventory ) and a measure of depression ( Beck Depression Inventory – II ) . Results Following intervention , the experimental group had greater improvements in fatigue , balance , and disability due to dizziness or disequilibrium compared with the exercise control group and the wait-listed control group . These results changed minimally at the 4-week follow-up . Limitations The study was limited by the small sample size . Further investigations are needed to determine the underlying mechanisms associated with the changes in the outcome measures due to the vestibular rehabilitation program . Conclusion A 6-week vestibular rehabilitation program demonstrated both statistically significant and clinical ly relevant change in fatigue , impaired balance , and disability due to dizziness or disequilibrium in patients with MS Multiple sclerosis ( MS ) patients suffer from impaired muscle activation and lower limb strength . Strength training enhances muscle activation and muscle strength , but neural adaptations to strength training remain unexplored in MS patients . The hypothesis was that maximal strength training ( MST ) using high loads and few repetitions would improve central neural drive and thus strength capacity of MS patients . 14 MS patients staying at a national MS rehabilitation center were r and omly assigned to a MST group or a control group ( CG ) . Both groups received “ today ’s treatment ” . In addition , the MST group trained 4 × 4 repetitions of unilateral dynamic leg press and plantar flexion 5 days a week for 3 weeks . Neural adaptations of the soleus muscle were assessed by surface electromyography ( EMG ) activity , and by superimposed H-reflexes and V-waves obtained during maximum voluntary isometric plantar flexor contractions ( MVCs ) . H-reflexes and V-waves were normalized by the M-wave ( HSUP/MSUP , V/MSUP , respectively ) . In the MST group , MVC increased by 20 ± 9 % ( P < 0.05 ) . Soleus EMG activity and V/MSUP ratio increased by 40 and 55 % , respectively , in the MST group compared to the CG ( P ≤ 0.05 ) . The HSUP/MSUP ratio remained unchanged . No change was apparent in the CG . MST group subjects were able to complete all training sessions . No adverse effects were reported . This r and omized study provides evidence that MST is effective of augmenting the magnitude of efferent motor output of spinal motor neurons in MS patients , alleviating some neuromuscular symptoms linked to the disease This study describes the effect of body-weight-supported treadmill training ( BWSTT ) on quality of life ( QoL ) for multiple sclerosis ( MS ) patients . Thirteen individuals with MS and gait impairment r and omly received two blocks of six biweekly training sessions : ( 1 ) robot-assisted BWSTT then BWSTT alone ( R-T ) or ( 2 ) BWSTT alone then robot-assisted BWSTT ( T-R ) . No statistically significant differences were found between robot-assisted BWSTT and unassisted BWSTT for improving QoL outcome measures . The change in Physical Component Summary scores from baseline to the end of the 12 training sessions improved significantly more in the R-T than the T-R group . Within-participant longitudinal changes in QoL for all participants from both groups combined showed significant improvements in 5 of the 13 QoL measures . The results of this pilot study suggest that both types of BWSTT may improve QoL for people with gait dysfunction secondary to MS Background : Multiple Sclerosis ( MS ) is a demyelinating disease of the nervous system which has numerous disabling effects on patients . Objectives : This study aim ed at investigating the short- and long-term effects of a period of combination exercise therapy on walking distance , balance , fatigue and quality of life in multiple sclerosis patients referred to the physiotherapy clinic of Iran 's Multiple Sclerosis Society in 2013 . Patients and Methods : This study was a r and omized controlled clinical trial on 59 patients divided into the intervention ( n = 39 ) and control groups ( n = 20 ) . The intervention group received 10 weeks of combination therapy including aerobic , strengthening , balancing and stretching exercises . A week before , a week later and a year after the beginning of the exercises , both groups of patients received BBSS , six minute walking , Family Support Services ( FSS ) , Exp and ed Disability Status Scale ( EDSS ) and quality of life tests . The scores of two groups were then compared using statistical tests such as repeated measures ANOVA test . Results : The results indicated significant changes in the intervention group in comparison to the control group in the second phase of the study comparing to the first one for all tests except EDSS ( Mean difference scores of EDSS : -0.13 ) , P-value = 0.60 ; FSS : -6.9 , P-value = 0.02 , Mental Quality of Life ( QOL ) : 16.36 , P-value = 0.001 ; Physical QOL : 12.17 , P-value = 0.001 , six minute walking : 137.2 , P-value < 0.0001 ; and Berg : 3.34 , P-value < 0.0001 . These changes were not significant in the second phase of the study comparing to the third one ; however , they were again significant in the third phase comparing to the first phase of the study ( P < 0.05 ) . Conclusions : Exercise has significant effect on improving symptoms of multiple sclerosis , and cessation of exercise may cause recurrence of symptoms in the intervention group with a slope similar to that of the control group . Therefore , continuous rather than short period exercises have valuable symptomatic and supportive relief effects in patients Background . Multiple sclerosis ( MS ) is a chronic demyelinating neurological disease . Several studies have reported that complementary and alternative therapies can have positive effects against pain in these patients . Objective . The objective was to investigate the effectiveness of an Ai-Chi aquatic exercise program against pain and other symptoms in MS patients . Methods . In this r and omized controlled trial , 73 MS patients were r and omly assigned to an experimental or control group for a 20-week treatment program . The experimental group underwent 40 sessions of Ai-Chi exercise in swimming pool and the control group 40 sessions of abdominal breathing and contraction-relaxation exercises in therapy room . Outcome variables were pain , disability , spasm , depression , fatigue , and autonomy , which were assessed before the intervention and immediately and at 4 and 10 weeks after the last treatment session . Results . The experimental group showed a significant ( P < 0.028 ) and clinical ly relevant decrease in pain intensity versus baseline , with an immediate posttreatment reduction in median visual analogue scale scores of 50 % that was maintained for up to 10 weeks . Significant improvements were also observed in spasm , fatigue , disability , and autonomy . Conclusion . According to these findings , an Ai-Chi aquatic exercise program improves pain , spasms , disability , fatigue , depression , and autonomy in MS patients Background The aim of this study was to evaluate the safety , feasibility and preliminary effects of a high-intensity rehabilitative task-oriented circuit training ( TOCT ) in a sample of multiple sclerosis ( MS ) subjects on walking competency , mobility , fatigue and health-related quality of life ( HRQoL ) . Methods 24 MS subjects ( EDSS 4.89 ± 0.54 , 17 female and 7 male , 52.58 ± 11.21 years , MS duration 15.21 ± 8.68 years ) have been enrolled and r and omly assigned to 2 treatment groups : ( i ) experimental group received 10 TOCT sessions over 2 weeks ( 2 hours/each session ) followed by a 3 months home exercise program , whereas control group did not receive any specific rehabilitation intervention . A feasibility patient-reported question naire was administered after TOCT . Functional outcome measures were : walking endurance ( Six Minute Walk Test ) , gait speed ( 10 Meter Walk Test ) , mobility ( Timed Up and Go test ) and balance ( Dynamic Gait Index ) . Furthermore , self-reported question naire of motor fatigue ( Fatigue Severity Scale ) , walking ability ( Multiple Sclerosis Walking Scale – 12 ) and health-related quality of life ( Multiple Sclerosis Impact Scale – 29 ) were included . Subjects ’ assessment s were delivered at baseline ( T0 ) , after TOCT ( T1 ) and 3 months of home-based exercise program ( T2 ) . Results After TOCT subjects reported a positive global rating on the received treatment . At 3 months , we found a 58.33 % of adherence to the home-exercise program . After TOCT , walking ability and health-related quality of life were improved ( p < 0.05 ) with minor retention after 3 months . The control group showed no significant changes in any variables . Conclusions This two weeks high-intensity task-oriented circuit class training followed by a three months home-based exercise program seems feasible and safe in MS people with moderate mobility impairments ; moreover it might improve walking abilities . Trial registration OBJECTIVE To examine the effects of an 8-week home-based resistance exercise program on balance , power , and mobility in adults with multiple sclerosis . DESIGN Experimental group design . SETTING General community . PARTICIPANTS Twenty-nine women ( age , 50.3+/-8.5 y ) and 8 men ( age , 51.1+/-7.1 y ) were stratified by disability level and age and were r and omized into exercise ( n=19 ) and control ( n=17 ) groups . INTERVENTION The exercise group had lower-extremity resistance training 3 times a week . The control group maintained current level of physical activity . Main outcome measures Primary outcome measures included balance , as measured by anteroposterior sway , mediolateral sway , and sway velocity using the AccuSway(PLUS ) force platform ; mobility as assessed with the Up and Go test ; and leg power as assessed with the Leg Extensor Power Rig . RESULTS Leg extensor power improved significantly in the exercise group ( pretest , 3.19+/-1.36 W/kg ; posttest , 3.95+/-1.23 W/kg ; P=.004 ) , although measures of balance and mobility did not change . CONCLUSIONS The home-based resistance program was well tolerated by participants and offered a practical means to improve leg extensor power in a short period of time Objective : To determine if exercise benefits patients with multiple sclerosis . Design : R and omized controlled trial . Setting s : Participants exercised at home and also attended exercise classes held in a hospital physiotherapy gym . Subjects : Thirty patients , diagnosed and independently mobile , were recruited in the Dublin area . Intervention : For three months , classes were held twice-weekly and participants exercised independently once-weekly . The control group was monitored monthly and management remained unchanged . Measurements : Measurements were taken at baseline , three and six months . The Modified Fatigue Impact Scale ( MFIS ) , Multiple Sclerosis Impact Scale-29 ( MSIS-29 ) and Functional Assessment of Multiple Sclerosis ( FAMS ) were used to measure fatigue and quality of life ( QOL ) . Heart rate ( HR ) and the Borg 's Rating of Perceived Exertion ( RPE ) were recorded during an incremental exercise test . The change from baseline scores between groups was compared using the Mann — Whitney U-test . Results : Twenty-four participants completed the programme ( n = 12 in each group ) . Based on the change in scores at three months , the exercise group had significantly greater improvements in exercise capacity ( HR : —14 [ -18.5 , -2.5 ] versus 0.5 [ -4 , 5.5 ] , P= 0.009 ) , QOL ( FAMS : 23 [ 9.5 , 42.5 ] versus -3.5 [ -16 , 5 ] , P=0.006 ) and fatigue ( MFIS : -13 [ -20 , -3 ] versus 1 [ -4 , 4.5 ] , P=0.02 ) . At six months , the difference in change scores remained significant for FAMS ( 19 [ 14 , 31 ] versus -4.5 [ -25 , 8 ] , P=0.002 ) and MFIS ( -8.5 [ -19.5 , -1 ] versus 0.5 [ -2.5 , 6.5 ] , P=0.02 ) only . Conclusions : A three-month exercise programme improved participants ' exercise capacity , QOL and fatigue , with the improvements in QOL and fatigue lasting beyond the programme Background and Purpose : Whole-body vibration ( WBV ) is a relatively new form of exercise training that may influence muscle performance . This study investigated the acute effects of high- ( 26 Hz ) and low- ( 2 Hz ) frequency WBV on isometric muscle torque of the quadriceps and hamstrings in persons with multiple sclerosis . Participants and Method : Fifteen individuals ( mean age = 54.6 years , SD = 9.6 ) with multiple sclerosis and Exp and ed Disability Status Scale scores ranging from 0 to 6.5 ( mean = 4.2 , SD = 2.3 ) participated in this r and omized , crossover study . After baseline measures of isometric quadriceps and hamstring muscle torque , subjects were exposed to 30 seconds of WBV at either 2 or 26 Hz . Torque values were measured again at one , 10 , and 20 minutes after vibration . Subjects returned one week later to repeat the same protocol at the alternate vibration frequency . Results : There were no significant differences in isometric torque production between the 2- and 26-Hz WBV conditions . There was also no significant difference between baseline torque values and those measured at one , 10 , and 20 minutes after either vibration exposure . However , there was a consistent trend of higher torque values after the 26-Hz WBV when compared with the 2-Hz condition for both quadriceps and hamstring muscles . Discussion and Conclusion : Although not statistically significant , peak torque values for both quadriceps and hamstring muscles were consistently higher after 30 seconds of WBV at 26 vs 2 Hz . Whether WBV presents a viable treatment option as either a warm-up activity or a long-term exercise intervention is yet to be determined . Future studies should include a wider variety of WBV parameters and the use of functional outcome measures Background There is a need for greater underst and ing of the impact of multiple sclerosis ( MS ) from the perspective of individuals with the condition . The South West Impact of MS Project ( SWIMS ) has been design ed to improve underst and ing of disease impact using a patient-centred approach . The purpose is to ( 1 ) develop improved measurement instruments for clinical trials , ( 2 ) evaluate longitudinal performance of a variety of patient-reported outcome measures , ( 3 ) develop prognostic predictors for use in individualising drug treatment for patients , particularly early on in the disease course . Methods This is a patient-centred , prospect i ve , longitudinal study of multiple sclerosis and clinical ly isolated syndrome ( CIS ) in south west Engl and . The study area comprises two counties with a population of approximately 1.7 million and an estimated 1,800 cases of MS . Self-completion question naires are administered to participants every six months ( for people with MS ) or 12 months ( CIS ) . Here we present descriptive statistics of the baseline data provided by 967 participants with MS . Results Seventy-five percent of those approached consented to participate . The male : female ratio was 1.00:3.01 ( n = 967 ) . Average ( st and ard deviation ) age at time of entry to SWIMS was 51.6 ( 11.5 ) years ( n = 961 ) and median ( interquartile range ) time since first symptom was 13.3 ( 6.8 to 24.5 ) years ( n = 934 ) . Fatigue was the most commonly reported symptom , with 80 % of participants experiencing fatigue at baseline . Although medication use for symptom control was common , there was little evidence of effectiveness , particularly for fatigue . Nineteen percent of participants were unable to classify their subtype of MS . When patient-reported subtype was compared to neurologist assessment for a sample of participants ( n = 396 ) , agreement in disease sub-type was achieved in 63 % of cases . There were 836 relapses , reported by 931 participants , in the twelve months prior to baseline . Twenty-three percent of the relapsing-remitting group and 12 % of the total sample were receiving disease-modifying therapy at baseline . Conclusions Demographics of this sample were similar to published data for the UK . Overall , the results broadly reflect clinical experience in confirming high symptom prevalence , with relatively little complete symptom relief . Participants often had difficulty in defining MS relapses and their own MS type Background : While there is an increasing body of evidence supporting the efficacy of exercise in people with multiple sclerosis ( MS ) , additional information on the effectiveness of combining aerobic and resistance training , and yoga is required . Objectives : This study evaluated the effectiveness of community exercise interventions for people with MS having minimal gait impairment . Methods : A multi-centred , block-r and omised , assessor-blinded , controlled trial was conducted . Participants were r and omised in groups of eight to physiotherapist (PT)-led exercise ( n = 80 ) , yoga ( n = 77 ) , fitness instructor (FI)-led exercise ( n = 86 ) and they took part in weekly community-based group exercise sessions . Those in the control group were asked not to change of their exercise habits ( n = 71 ) . The primary outcome was the Multiple Sclerosis Impact Scale ( MSIS ) 29v2 physical component , measured before and after the 10-week intervention . Secondary outcomes were the MSIS 29v2 psychological component , the Modified Fatigue Impact Scale ( MFIS ) and the 6-Minute Walk Test ( 6MWT ) . Results : The group x time interaction approached significance for the MSIS-29v2 physical component ( f = 2.48 , p = 0.061 ) and MFIS total ( f = 2.50 , p = 0.06 ) , and it was significant for the MFIS physical subscale ( f = 4.23 , p = 0.006 ) . All three exercise interventions led to a statistically significant improvement on the MSIS-29 psychological component and both the MFIS total and physical subscales , which were greater than the control ( p < 0.05 ) . Only the PT-led and FI-led interventions significantly improved the MSIS-29 physical and 6MWT to levels greater than the control ( p < 0.05 ) . Conclusions : This study provides evidence for the positive effect of exercise on the physical impact of MS and fatigue . The group nature of the classes may have contributed to the positive effects seen on the psychological impact of MS Objective : To establish the effects of a 12-week , community-based group exercise intervention for people moderately affected with multiple sclerosis . Design : R and omized controlled pilot trial . Setting : Two community leisure centres . Participants : Thirty-two participants with multiple sclerosis r and omized into intervention or control groups . Intervention : The intervention group received 12 weeks of twice weekly , 60-minute group exercise sessions , including mobility , balance and resistance exercises . The control group received usual care . Main outcome measures : An assessor blinded to group allocation assessed participants at baseline , after eight weeks and after 12 weeks . The primary outcome measure was 25-foot ( 7.6 m ) walk time , secondary outcomes assessed walking endurance , balance , physical function , leg strength , body mass index , activity levels , fatigue , anxiety and depression , quality of life and goal attainment . Results : The intervention made no statistically significant difference to the results of participants ’ 25-foot walk time . However the intervention led to many improvements . In the intervention group levels of physical activity improved statistically between baseline and week 8 ( P < 0.001 ) and baseline and week 12 ( P = 0.005 ) . Balance confidence results showed a significant difference between baseline and week 12 ( P = 0.013 ) . Good effect sizes were found for dynamic balance ( d = 0.80 ) , leg strength ( d = 1.33 ) , activity levels ( d = 1.05 ) and perceived balance ( d = 0.94 ) . Conclusion : The results of the study suggest that community-based group exercise classes are a feasible option for people moderately affected with multiple sclerosis , and offer benefits such as improved physical activity levels , balance and leg strength Reliability estimates are important parameters for power analyses and sample -size calculations in behavioral interventions for increasing physical activity among persons with multiple sclerosis ( MS ) . This study involved a secondary data analysis for providing reliability estimates for measures of physical activity over a six-month period in MS . On two occasions separated by six months , participants completed the Godin Leisure-Time Exercise Question naire ( GLTEQ ) and wore an ActiGraph model 7164 accelerometer on a belt around the waist for a seven-day period . The outcomes from the accelerometer were total activity counts and minutes of moderate-to-vigorous physical activity ( MVPA ) per day . The main analyses involved two-way , r and om effects intraclass correlation coefficients ( ICCs ) . The ICCs for GLTEQ scores , total activity counts , and minutes of MVPA were .66 , .84 , and .84 , respectively . Additionally , the sample was less physically active than adults without MS , and correlation analyses supported the validity of the measures , but within a substantially larger sample . Overall , the measures had acceptable , but different , reliability over six months in this sample of mostly women with relapsing – remitting MS . Power analyses using the reliability estimates indicated vastly different sample sizes for the measures of physical activity and when compared with the default parameter in software packages Fifty‐four multiple sclerosis ( MS ) patients were r and omly assigned to exercise ( EX ) or nonexercise ( NEX ) groups . Before and after 15 weeks of aerobic training , aspects of fitness including maximal aerobic capacity ( Vo2max ) , isometric strength , body composition , and blood lipids were measured . Daily activities , mood , fatigue , and disease status were measured by the Profile of Mood States ( POMS ) , Sickness Impact Profile ( SIP ) , Fatigue Severity Scale ( FSS ) , and neurological examination . Training consisted of 3 × 40‐minute sessions per week of combined arm and leg ergometry . Exp and ed Disability Status Scale ( EDSS ) scores were unchanged , except for improved bowel and bladder function in the EX group . Compared with baseline , the EX group demonstrated significant increases in Vo2max , upper and lower extremity strength , and significant decreases in skinfolds , triglyceride , and very‐low‐density lipoprotein ( VLDL ) . For the EX group , POMS depression and anger scores were significantly reduced at weeks 5 and 10 , and fatigue was reduced at week 10 . The EX group improved significantly on all components of the physical dimension of the SIP and showed significant improvements for social interaction , emotional behavior , home management , total SIP score , and recreation and past times . No changes were observed for EX or NEX groups on the FSS . Exercise training result ed in improved fitness and had a positive impact on factors related to quality of life Abstract Regular exercise is important for patients with multiple sclerosis ( MS ) to maintain their functional ability and general health . The aim of this study was to determine whether a long – term exercise program has any effect on functional impairment or healthrelated quality of life ( HRQOL ) in subjects with mild to moderate MS . In a r and omised controlled trial , subjects in the intervention group ( n = 47 ) exercised according to a progressive exercise program , mainly consisting of resistance training , for six months . Subjects in the control group ( n = 48 ) received no intervention . The subjects were assessed at baseline and at six months using the Multiple Sclerosis Functional Composite ( MSFC ) , the Exp and ed Disability Status Scale ( EDSS ) , the Functional Independence Measure ( FIM ) , the MS Quality of Life–54 ( MSQOL–54 ) question naire and the Centre for Epidemiologic Studies Depression Scale ( CES – D ) . The drop – out rate was low ( 4 % ) with 91 subjects completing the study . At six months , the exercising subjects showed improvement on the MSFC ( mean score change 0.114 , 95 % confidence interval [ CI ] 0.010 to 0.218 ) , whereas the control subjects showed deterioration ( mean score change –0.128 , 95 % CI –0.232 to –0.025 ) . The change between groups was statistically significant ( interaction , p = 0.001 ) . Consistent with the physical nature of the intervention , the change predominantly occurred in leg function/ambulation . The effect seen in the EDSS , FIM , MSQOL–54 or CES – D was nil . These findings indicate that MSFC is more sensitive than EDSS in the detection of improvement in functional impairment as a result of regular exercise . The unfavourable results from HRQOL do not rule out the possibility that other types of exercise programs may improve it in MS Abstract .It is well known that neurorehabilitation can reduce disability or improve h and icap of people with multiple sclerosis ( MS ) . The aim of this study was to evaluate the effectiveness of a short period ( 6 weeks ) of a tailored , individualised outpatient rehabilitation program in people with progressive MS . A r and omised-controlled trial was undertaken in patients with primary and secondary progressive MS referred to the Centro Sclerosi Multipla of Catania . One hundred and eleven patients were assessed at baseline and at 12 weeks with vali date d measures of disability ( Functional Independence Measure ( FIM ) ) and impairment ( Exp and ed Disability Status Scale ( EDSS ) and Functional Systems Scale ) . Of the 111 , 58 were r and omly assigned to the treatment group and 53 to the control group . All patients had been previously trained in a home exercise program . Both groups were well matched for age , sex , disease duration and severity , disability and quality of life ( Short Form-36 ) . At the end of 6 weeks patients allocated to the rehabilitation treatment group showed significant improvement in their level of disability compared with the control group , while the level of impairment did not change . Thirty-two patients of the treatment group and four of the control group improved on the FIM by two or more steps at 12 weeks ( p<0.0001 ) . An improvement by 1 EDSS step occurred in only two patients of the treatment group and in one patient of the control group . Benefits were maintained for a further six weeks . This study demonstrates that a short outpatient rehabilitation treatment improves disability of MS patients , without changing their impairment and confirms the effectiveness of rehabilitation in people with MS Objective : The purpose of this study was to compare adaptations in functional and quality of life measures following endurance- and resistance-exercise training in people with multiple sclerosis . Design : Cross-over design with an eight-week washout period . Setting : Community health centre . Subjects : Sixteen individuals with multiple sclerosis . Intervention : Subjects completed both an eight-week endurance- and an eight-week resistance-exercise training programme in a r and omized order . The exercise training comprised individualized progressive programmes that were completed twice weekly in a supervised group setting . Main measures : Grip strength , functional reach , four step square , timed up and go and six-minute walk tests , Multiple Sclerosis Impact and Modified Fatigue Impact Scales , Becks Depression Inventory and the Health Status Question naire Short Form-36 . Results : Sixteen of 21 ( 76 % ) subjects completed the study . Subjects attended 13.2 ± 1.6 endurance- and 15.8 ± 1.9 resistance-exercise training sessions . No adverse events were reported . No significant differences ( P < 0.05 ) in any outcome measures were observed between the two exercise training programmes either at baseline or following the completion of both training programmes . Conclusion : Both endurance- and resistance-exercise training were well tolerated and appear to provide similar effects for people with multiple sclerosis , but larger studies are required to confirm these findings Background and Purpose Physical deconditioning is involved in the impaired exercise tolerance of patients with multiple sclerosis ( MS ) , but data on the effects of aerobic training ( AT ) in this population are scanty . The purpose of this study was to compare the effects of an 8-week AT program on exercise capacity — in terms of walking capacity and maximum exercise tolerance , as well as its effects on fatigue and health-related quality of life — as compared with neurological rehabilitation ( NR ) in subjects with MS . Subjects and Methods Nineteen subjects ( 14 female , 5 male ; mean age [X̄±SD]=41±8 years ) with mild to moderate disability secondary to MS participated in a r and omized crossover controlled study . Eleven subjects ( 8 female , 3 male ; mean age [X̄±SD]=44±6 years ) completed the study . Results After AT , but not NR , the subjects ’ walking distances and speeds during a self-paced walk were significantly improved , as were their maximum work rate , peak oxygen uptake , and oxygen pulse during cardiopulmonary exercise tests . The increases in peak oxygen uptake and maximum work rate , but not in walking capacity , were significantly higher after AT , as compared with after NR . Additionally , the subjects who were most disabled tended to benefit more from AT . There were no differences between AT and NR in effects on fatigue , and the results showed that AT may have partially affected health-related quality of life . Discussion and Conclusion The results suggest that AT is more effective than NR in improving maximum exercise tolerance and walking capacity in people with mild to moderate disability secondary to MS OBJECTIVE To evaluate whether inspiratory muscle training ( IMT ) improves inspiratory muscle strength , respiratory capacity , fatigue , and subjective perception of physical endurance in patients with advanced multiple sclerosis ( MS ) . DESIGN R and omized controlled trial . SETTING Outpatient clinic in Sweden . PARTICIPANTS Fifteen severely disabled patients with MS , r and omized to a training or control group . INTERVENTION Seven patients trained with a Threshold inspiratory muscle trainer , twice every other day , with 3 sets of 10 loaded inspirations ( 40%-60 % of patients ' maximal inspiratory pressure [ Pimax ] ) over a 10-week period . MAIN OUTCOME MEASURES Spirometry , Pimax , maximal expiratory pressure ( Pemax ) , clinical assessment s , and question naires on the patients ' fatigue severity and physical endurance were evaluated . RESULTS After training , the Pimax ( P<.008 ) and Pemax ( P<.02 ) increased in the training group . The improvement in Pimax after 10 weeks of training was higher than the improvement in the control group ( P<.01 ) and was maintained 1 month after the training period ended . The training affected neither respiratory function nor the patients ' symptoms . CONCLUSIONS IMT had a beneficial effect on inspiratory muscle strength in patients with MS and is recommended as a complement to ordinary physical training Background : Exercise may have beneficial effects on both well-being and walking ability in multiple sclerosis ( MS ) . Exercise is shown to be neuroprotective in rodents and may also enhance cognitive function in humans . It may , therefore , be particularly useful for MS patients with pronounced neurodegeneration . Objective : To investigate the potential of st and ardized exercise as a therapeutic intervention for progressive MS , in a r and omized-controlled pilot trial . Methods : Patients with progressive MS and moderate disability ( Exp and ed Disability Status Scale ( EDSS ) of 4–6 ) were r and omized to one of three exercise interventions ( arm ergometry , rowing , bicycle ergometry ) for 8–10 weeks or a waitlist control group . We analyzed the drop-out rate as a measure of feasibility . The primary endpoint of the study was aerobic fitness . Secondary endpoints were walking ability , cognitive function as measured by a neuropsychological test battery , depression and fatigue . Results : A total of 42 patients completed the trial ( 10.6 % drop-out rate ) . Significant improvements were seen in aerobic fitness . In addition , exercise improved walking ability , depressive symptoms , fatigue and several domains of cognitive function . Conclusion : This study indicated that aerobic training is feasible and could be beneficial for patients with progressive MS . Larger exercise studies are needed to confirm the effect on cognition . Trial Registration : IS RCT N ( trial number 76467492 ) http://is rct Objective : To explore the effectiveness of breathing-enhanced upper extremity exercises on the respiratory function of patients with multiple sclerosis . Design : R and omized controlled study of six-week duration . Subjects : Forty patients with multiple sclerosis ( age 39.2 ± 7 years ; Kurtzke Exp and ed Disability Status Scale scores : 4.51 ± 1.55 ) r and omly divided into two groups . Methods : The training group followed a six-week home training programme design ed to strengthen accessory respiratory muscles . Controls performed no exercises . All subjects su bmi tted to baseline and post-training tests of spirometry , respiratory muscle strength and 6-minute walking . They were also assessed with pulmonary dysfunction and exertion fatigue indices . Results : Spirometry revealed clear improvement in forced expiratory volume in 1 second ( FEV 1 ) ( + 13 % , P = 0.003 ) result ing in higher FEV1/FVC ( forced vital capacity ) ( + 8.5 % , P = 0.03 ) . Maximal inspiratory pressure ( P Imax ) increased by + 7.1 % but not significantly . Maximal expiratory pressure ( P Emax ) and FVC were significantly higher ( by + 7.1 % , P = 0.0066 and + 4.8 % , P = 0.036 respectively ) with respect to baseline measures . Pulmonary dysfunction was reduced ( —9 % , P = 0.002 ) while 6-minute walking distance was longer ( + 16 % , P = 0.029 ) at equal exertion fatigue level . Conclusions : The programme improved most pulmonary performance measures and had clinical significance . Its sustained application may prevent respiratory complications frequently observed in the later stages of multiple sclerosis OBJECTIVES Spasticity , cognitive impairment , depression and fatigue significantly reduce the quality of life in multiple sclerosis ( MS ) patients . To find out whether nonpharmalogical treatment approaches can reduce these symptoms we investigated effects of sports climbing ( SC ) and yoga on spasticity , cognitive impairment , mood change and fatigue in MS patients . Sports climbing ( SC ) and yoga are aerobic physical activities comprised a series of stretching techniques , implementation of which dem and s body control and planning of complex movements . MATERIAL S AND METHODS 20 subjects with relapsing-remitting or progressive MS , 26 - 50 years of age , with EDSS < or=6 and EDSS pyramidal functions score (EDSSpyr)>2 were enrolled in a r and omized prospect i ve study . The participants were r and omly divided into SC and yoga group . We evaluated spasticity , cognitive function , mood and fatigue before and after both programs , that lasted 10 weeks , with st and ardized assessment methods . RESULTS There were no significant improvements in spasticity after SC and yoga . In the SC group we found a 25 % reduction ( p=0.046 ) in EDSSpyr . There were no differences in executive function after the completion of both programs . There was a 17 % increase in selective attention performance after yoga ( p=0.005 ) . SC reduced fatigue for 32.5 % ( p=0.015 ) , while yoga had no effect . We found no significant impact of SC and yoga on mood . CONCLUSIONS Yoga and SC might improve some of the MS symptoms and should be considered in the future as possible complementary treatments OBJECTIVES The aim of this study is to evaluate the effects of calisthenic exercises on balance , walking speed , fatigue , quality of life , and psychological status in patients with Multiple Sclerosis ( MS ) . PATIENTS AND METHODS Forty patients diagnosed with MS were r and omized into two exercise groups ( group 1 = hospital-based , group 2 = home-based ) . Outcome measures including the MS International Quality of Life Scale , 10-meter walking test , Berg Balance Scale , Fatigue Severity Scale and the Hospital Anxiety Depression Inventory were assessed at the baseline and at 12-weeks . RESULTS Thirty-six participants completed the exercise programme ( hospital based = 16 , home based = 20 ) . The mean age was 32.83 ± 3.64 years . The mean duration of disease was 6.97 ± 3.15 years . Hospital-based and home-based exercise groups had significant improvements in the balance , 10-meter walking test , anxiety , and the quality of life after the 12-week exercise programme . There was a significant improvement in the hospital-based patients in terms of the depression scores . No significant improvement was observed in terms of fatigue in any of the groups . When both groups were compared , the improvement in the balance and depression scores of the hospital-based patients was significantly higher than the home-based patients . CONCLUSIONS Calisthenic exercises can be easily performed both at home and in hospital setting . In patients with MS , calisthenic exercises performed at home or at the hospital may improve the balance , quality of life , and the functional and psychological status , while no significant effect has been observed on fatigue In recent years it has become clear that multiple sclerosis ( MS ) patients benefit from physical exercise as performed in aerobic training but little is known about the effect on functional domains and physiological factors mediating these effects . We studied immunological , endocrine and neurotrophic factors as well as coordinative function and quality of life during an 8-week aerobic bicycle training in a waitlist control design . In the immune-endocrine study ( 1 ) 28 patients were included , the coordinative extension study ( 2 ) included 39 patients . Training was performed at 60 % VO(2)max after determining individual exertion levels through step-by-step ergometry . Metabolic ( lactate ) , endocrine ( cortisol , adrendocortico-releasing hormone , epinephrine , norepinephrine ) , immune ( IL-6 , soluble IL-6 receptor ) , and neurotrophic ( brain-derived neurotrophic factor ( BDNF ) , nerve growth factor ( NGF ) ) parameters were compared from a pre study and a post study endurance test at 60 % VO(2)max for 30 min . In study ( 1 ) , lowered lactate levels despite higher workload levels indicated a training effect . Disease-specific quality of life ( as measured by the Hamburg Quality of Life Question naire for Multiple Sclerosis , HAQUAMS ) significantly increased in the training group . No significant training effects were seen for endocrine and immune parameters or neurotrophins . In study ( 2 ) , two out of three coordinative parameters of the lower extremities were significantly improved . In summary , low-level aerobic training in MS improves not only quality of life but also coordinative function and physical fitness Exercise therapy ( ET ) can be beneficial in disabled multiple sclerosis ( MS ) patients . Intermittent transcranial magnetic theta burst stimulation ( iTBS ) induces long-term excitability changes of the cerebral cortex and may ameliorate spasticity in MS . We investigated whether the combination of iTBS and a program of ET can improve motor disability in MS patients . In a double-blind , sham-controlled trial , 30 participants were r and omized to three different interventions : iTBS plus ET , sham stimulation plus ET , and iTBS alone . Before and after 2 weeks of treatment , measures of spasticity through the modified Ashworth scale ( MAS ) and the 88 items Multiple Sclerosis Spasticity Score question naire ( MSSS-88 ) , fatigue through the Fatigue Severity Scale ( FSS ) , daily living activities ( ADL ) through the Barthel index and health-related quality of life ( HRQoL ) through the 54 items Multiple Sclerosis Quality of life inventory ( MSQoL-54 ) were collected . iTBS plus ET reduced MAS , MSSS-88 , FSS scores , while in the Barthel index and MSQoL-54 , physical composite scores were increased . iTBS alone caused a reduction of the MAS score , while none of the measured scales showed significant changes after sham iTBS plus ET . iTBS associated with ET is a promising tool for motor rehabilitation of MS patients Background : Preservation of locomotor activity in multiple sclerosis ( MS ) patients is of utmost importance . Robotic-assisted body weight-supported treadmill training is a promising method to improve gait functions in neurologically impaired patients , although its effectiveness in MS patients is still unknown . Objective : To compare the effectiveness of robot-assisted gait training ( RAGT ) with that of conventional walking treatment ( CWT ) on gait and generalized functions in a group of stable MS patients . Methods : A prospect i ve r and omized controlled trial of 12 sessions of RAGT or CWT in MS patients of EDSS score 5–7 . Primary outcome measures were gait parameters and the secondary outcomes were functional and quality of life parameters . All tests were performed at baseline , 3 and 6 months post-treatment by a blinded rater . Results : Fifteen and 17 patients were r and omly allocated to RAGT and CWT , respectively . Both groups were comparable at baseline in all parameters . As compared with baseline , although some gait parameters improved significantly following the treatment at each time point there was no difference between the groups . Both FIM and EDSS scores improved significantly post-treatment with no difference between the groups . At 6 months , most gait and functional parameters had returned to baseline . Conclusions : Robot-assisted gait training is feasible and safe and may be an effective additional therapeutic option in MS patients with severe walking disabilities OBJECTIVE To investigate the feasibility and preliminary outcomes of a home progressive resistance training ( PRT ) program augmented by neuromuscular electrical stimulation ( NMES ) . DESIGN R and omized controlled pilot trial . SETTING Participant homes . PARTICIPANTS People with multiple sclerosis ( MS ) ( N=37 ) who use a walking aid . INTERVENTIONS A 12-week home PRT program or the same program augmented by NMES . MAIN OUTCOME MEASURES Strength using h and -held dynamometry ; repeated sit to st and test ; Berg Balance Scale ; timed Up & Go test ; 12-Item Multiple Sclerosis Walking Scale ; Multiple Sclerosis Impact Scale-29 , version 2 ; and Modified Fatigue Impact Scale ( MFIS ) . The NMES group also completed a device usability question naire . RESULTS Only change in MFIS score was significantly greater in the NMES group than the PRT group ( P=.012 ) . The NMES group improved significantly in quadriceps endurance ( median of change , 8.5 ; P=.043 ) , balance ( median of change , 3.5 ; P=.001 ) , physical impact of MS ( median of change , -8.3 ; P=.001 ) , and impact of fatigue ( median of change , -17 ; P=.001 ) . Participants rated the device as highly usable . CONCLUSIONS This pilot study suggests that a home PRT program with NMES is feasible , and the neuromuscular electrical stimulation device is usable by this population . Only reduction in impact of fatigue was greater in the NMES than the PRT group BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . BACKGROUND Fatigue is a common and disabling symptom in patients with multiple sclerosis ( MS ) . Underlying mechanisms postulated so far have involved localization of brain lesions and abnormalities of the neuroendocrine system and cytokine regulation . OBJECTIVE To investigate the relationship between fatigue and the hypothalamo-pituitary-adrenal ( HPA ) axis in patients with MS . DESIGN A prospect i ve survey . SETTING Outpatient and inpatient study at the Max Planck Institute of Psychiatry , Munich , Germany . PATIENTS Thirty-one patients with clinical ly definite MS , a relapsing-remitting disease course , and without MS-specific treatment . INTERVENTIONS Assessment of fatigue with 3 question naires : the Fatigue Severity Scale ( FSS ) , the Modified Fatigue Impact Scale ( MFIS ) , and the Visual Analog Scale . Assessment of HPA axis regulation with the combined dexamethasone-corticotropin releasing hormone ( Dex-CRH ) test . RESULTS The FSS score was significantly correlated with the MFIS score . Patients with fatigue had significantly elevated adrenocorticotropin ( ACTH ) levels in the combined Dex-CRH test . CONCLUSIONS In contrast to results for chronic fatigue syndrome , where a hyporeactivity of the HPA axis has been shown , MS patients with fatigue exhibited a higher activity of the HPA axis than those without fatigue , as evidence d by significantly increased ACTH concentrations . Proinflammatory cytokines , known to be elevated in patients with MS , may cause both HPA axis alterations and fatigue Background : The most effective exercise dose has yet to be established for multiple sclerosis ( MS ) . Objective : The aim of this study was to investigate the effect of different exercise intensities in people with MS . Methods : We completed a r and omized comparator study of three cycling exercise intensities , with blinded assessment , was carried out in Oxford . Sixty-one adults with MS who fulfilled inclusion criteria were r and omized at entry into the study , using a computer-generated list held by an exercise professional , into either : continuous ( at 45 % peak power , n = 20 ) , intermittent ( 30 sec on , 30 sec off at 90 % peak power , n = 21 ) or combined ( 10 min intermittent at 90 % peak power then 10 min continuous at 45 % peak power , n = 20 ) exercise for 20 min twice a week for 12 weeks in a leisure facility . Groups were assessed at : baseline , halfway ( 6 weeks ) , end intervention ( 12 weeks ) and follow-up ( 24 weeks ) . Primary outcome measure was 2 min walk . Results : Fifty-five participants were included in the analysis ( n = continuous 20 , intermittent 18 , combined 17 ) . No differences were found between groups . After 6 weeks , considering all participants , 2 min walk distance increased by 6.96 ± 2.56 m ( 95 % CI : 1.81 to 12.10 , effect size ( es ) : 0.25 , p < 0.01 ) . The continuous group increased by 4.71 ± 4.24 m ( 95 % CI : −3.80 to 13.22 , es : 0.06 ) , intermittent by 12.94 ± 4.71 m ( 95 % CI : 3.97 to 21.92 , es : 0.28 ) and combined by 3.22 ± 4.60 m ( 95 % CI : −6.01 to 12.46 , es : 0.04 ) . Two minute walk did not significantly change between further assessment s. Between 6 and 12 weeks there was a drop in attendance that seemed to be associated with the intermittent and combined groups ; these groups also had a greater number of adverse events ( leg pain during cycling most common ) and dropouts ( n = continuous 1 , intermittent 5 , combined 10 ) . Considering all participants , 6 weeks of cycling exercise produced benefits in mobility that were maintained with further sessions . Conclusion : While no differences were found between groups , greater benefit may be associated with higher-intensity exercise , but this may be less well tolerated . CONSORT - trial registration number ( IS RCT N89009719 Brain-derived neurotrophic factor ( BDNF ) and insulin-like growth factor (IGF)-1 , support brain health through protective , regenerative and adaptive neural processes . In this study , we investigated whether exercise and exercise training would alter circulating BDNF and IGF-1 in people with multiple sclerosis ( MS ) and matched controls . Twenty-two volunteers ( MS ( n = 11 ) and controls ( n = 11 ) ) matched in age , weight , body fatness and aerobic capacity ( VO2peak ) completed the study . Subjects cycled at 60 % of VO2peak , three times per week for 8 weeks . Serum was analyzed for BDNF and IGF-1 at rest and BDNF after a st and ardized exercise bout at weeks 0 , 4 and 8 . Resting BDNF levels were lower in MS compared to controls at week 0 ( p = 0.03 ) and only tended to be lower at week 8 ( p = 0.07 ) . BDNF increased at week 4 in MS subjects ( p = 0.04 ) and returned to baseline at week 8 . With acute exercise , BDNF decreased in both groups during the 3-hour post-exercise recovery period . Resting IGF-1 concentration was not significantly different between groups before or after training . Our study provides preliminary evidence that exercise may influence BDNF regulation in humans . Further research is needed to eluci date the impact of exercise on neurotrophin production , secretion and target tissue responses in humans Background : Although there are many studies evaluating exercise interventions , few studies have evaluated the effect at follow-up . Objectives : This paper presents follow-up data for participants who completed the exercise interventions in a large r and omised controlled trial . Methods : One hundred twenty-one people with multiple sclerosis ( MS ) with minimal gait impairment who completed 10 weeks of community-based exercise interventions were evaluated by a blinded assessor 12 weeks after the intervention . The primary outcome measure was the Multiple Sclerosis Impact Scale-29 version 2 ( MSIS-29,v2 ) physical component . Other outcomes were the MSIS-29 psychological component , the Modified Fatigue Impact Scale ( MFIS ) and the 6-minute walk test ( 6MWT ) distance . Results : The positive effect on the physical impact of MS was not maintained from baseline to follow-up ( −1.6 , 95 % CI −0.8 , 4.0 , p=0.189 ) . The psychological impact and the impact of fatigue remained significantly improved ( −3.5 , 95 % CI −6.1 , −1.0 , p = 0.006 and −4.68 , 95 % CI −6.9 , −2.5 , p < 0.001 , respectively ) . There was no time effect for the 6MWT ( f = 1.76 , p = 0.179 ) although the trend suggests reversal of the benefits gained from the physiotherapist (PT)- and fitness instructor (FI)-led intervention . Conclusion : The maintained benefit on the psychological impact of MS and fatigue may have important personal and socioeconomic consequences ; however , it is important to find ways to maintain the physical benefits of exercise over the long term Background : Few high- quality trials have examined the effects of progressive resistance training ( PRT ) on people with multiple sclerosis ( MS ) . Objective : To determine the effectiveness of PRT for people with MS , focusing on improving the gait deficits common in this population . Methods : Using a single blind r and omized controlled trial , people with relapsing – remitting MS were r and omly allocated to either a PRT program targeting the lower limb muscles twice a week for 10 weeks ( n = 36 ) , or usual care plus an attention and social program conducted once a week for 10 weeks ( n = 35 ) . Outcomes were recorded at baseline , week 10 and week 22 . Results : Participants attended 92 % of training sessions , with no serious adverse events . At 10 weeks , no differences were detected in walking performance . However , compared with the comparison group PRT demonstrated increased leg press strength ( 16.8 % , SD 4.5 ) , increased reverse leg press strength ( 29.8 % , SD 12.7 ) , and increased muscle endurance of the reverse leg press ( 38.7 % , SD 32.8 ) . Improvements in favor of PRT were also found for physical fatigue ( Mean difference −3.9 units , 95%CI −6.6 to −1.3 ) , and the physical health domain of quality of life ( Mean difference 1.5 units , 95%CI 0.1 to 2.9 ) . At week 22 almost no between-group differences remained . Conclusion : PRT is a relatively safe intervention that can have short-term effects on reducing physical fatigue , increasing muscle endurance and can lead to small improvements in muscle strength and quality of life in people with relapsing – remitting MS . However , no improvements in walking performance were observed and benefits do not appear to persist if training is completely stopped Purpose . Compare the efficacy of two interventions design ed to promote health and physical activity ( PA ) . Design . This study was a r and omized clinical trial using a time series design . Subjects were r and omized into individualized physical rehabilitation ( IPR ) and group wellness intervention ( GWI ) . Primary question naires were administered twice preintervention and twice postintervention . Physical fitness and PA frequency were assessed preintervention and postintervention . Setting . Clinic based in a metropolitan area . Subjects . Fifty volunteers with multiple sclerosis . Interventions . IPR consisted of four physical therapy sessions plus three telephone calls . GWI consisted of seven educational sessions . Measures . Primary : SF-36 Health Survey , Modified Fatigue Impact Scale , Mental Health Inventory . Secondary : physical assessment , PA frequency . Analysis . Stability of primary question naires between the two pretests was examined . Efficacy of interventions was evaluated by multivariate analysis of variance ( MANOVA ) and effect sizes . Results . Primary measures were stable between pretests . MANOVA showed nonsignificant differences between interventions . Eight weeks postintervention , both groups had improved PA , fatigue , resting heart rate , and strength . Effect sizes suggested that IPR had a greater effect on preventing decline of physical health , whereas GWI had a greater effect on improving mental health . Conclusion . Preliminary evidence indicated that health and PA improved in both groups . Effect sizes suggested that participants benefited more physically from IPR and more mentally from GWI . Future research should determine whether combining therapeutic exercise with group education improves both mental and physical health Background : Exercise therapy in persons with multiple sclerosis ( MS ) is effective for improving muscle strength and functional mobility . Objective : To investigate , in MS patients attending an in-patient rehabilitation program , the additional effects of a 3-week exercise program , performed on a whole body vibration platform , on muscle strength and functionality . Methods : Median Exp and ed Disability Status Scale ( EDSS ) of participating patients was 5.5 . This r and omized controlled trial differentiated a MS control group ( n = 17 ) and two exercise groups performing exercises on a vibration platform ( WBV-full group , n = 20 ) and on the platform additionally covered by a damping mat ( WBV-light group , n = 18 ) . Exercise groups performed , during 10 training sessions , six static and dynamic exercises st and ing on a platform vibrating at high frequency and low amplitude . Isometric muscle strength of quadriceps , hamstrings , tibialis anterior and gluteus medius was measured with a h and -held dynamometer . Functional mobility was measured with Berg Balance Scale ( BBS ) , 3-minute walk test and Timed Get up and Go test . Results : Eight drop-outs occurred in the exercise groups ( WBV-full = 4 , WBV-light = 4 ) , but were unrelated to WBV as type of intervention . Across groups , significant time effects were found for all muscle groups . For maximal quadriceps and hamstrings muscle strength , interaction effects were found with post-hoc tests indicating exercise group-significant improvements in the WBV-full group only . Significant time effects were found for all functional tests . Improvements on the BBS and 3-minute walk test were larger in training than in control groups , but no significant interactions were found . Conclusions : A 3-week exercise program on a vibration plate significantly improved muscle strength , but not functionality , in persons with MS This pilot study investigated whether 4 weeks of aerobic treadmill training in individuals with multiple sclerosis ( MS ) improved mobility and reduced fatigue . Individuals with MS were recruited to this prospect i ve , r and omised controlled trial . Individuals were assessed at baseline , week 7 and 12 with a 10 metre timed walk , a 2 minute walk , the Rivermead Mobility Index , and the Fatigue Severity Scale . After a pre- assessment familiarisation session and a baseline assessment , individuals were r and omly allocated to an initial intervention or delayed intervention group . Treadmill training consisted of 4 weeks of supervised aerobic exercise delivered weeks 3–6 in the immediate group and 8–11 in the delayed group . Of the initial 19 recruits , 16 individuals completed the study . There was a significant difference in walking endurance between the delayed and immediate groups at baseline ( p<0.05 ) . On re assessment in week 7 , decreases in 10 metre walk time were found in both groups , which was significant in the immediate group ( p<0.05 ) . The 2 minute walk distance significantly increased in both groups ( p<0.05 ) . In the training group , reassessed at week 12 after training ceased , there was a return towards baseline scores . No significant changes in fatigue scores were found . This study showed that in individuals with MS , aerobic treadmill training is feasible and well tolerated . Walking speed and endurance increased following training with no increase in reported fatigue . Detraining occurred in the period following training . A larger r and omised clinical trial is warranted Multiple sclerosis ( MS ) patients of an inpatient rehabilitation program have been r and omly assigned to an exercise training ( MS-ET ) or nontraining group ( MS-NI ) . Before and after 4 weeks of aerobic exercise training , a grade d maximal exercise test with measurement of gas exchange and a lung function test was administered to all 26 patients fulfilling the inclusion criteria . Activity level , fatigue and health perception were measured by means of question naires . Twenty-six healthy persons served as control group and were matched in respect of age , gender and activity level . Training intervention consisted of 5 × 30 min sessions per week of bicycle exercise with individualised intensity . Compared with baseline , the MS training group demonstrated a significant rightward placement of the aerobic threshold ( AT ) ( VO2 + 13 % ; work rate [WR])+11 % ) , an improvement of health perception ( vitality+46 % ; social interaction+36 % ) , an increase of activity level ( + 17 % ) and a tendency to less fatigue . No changes were observed for the MS-NI group and the control groups . Maximal aerobic capacity and lung function were not changed by either training or nontraining in all four groups . Overall compliance to the training program was quite low ( 65 % ) , whereas incidence of symptom exacerbation by physical activity has been lower than expected ( 6 % ) Since the earliest descriptions psychological and physical stress has been considered a controversial but potentially important factor in the onset and course of multiple sclerosis ( MS ) . During recent years it has become clear that MS patients benefit from physical exercise as performed in aerobic training . As acute exercise has profound effects on immune and endocrine parameters we studied endocrine and immune response to st and ardized physical stress in MS within a study of aerobic training . Fifteen MS patients completed an eight-week aerobic training program , 13 patients were part of a wait-control group . Twenty healthy controls were recruited as well . A step-by-step bicycle ergometry was performed to determine individual exertion levels . For the endurance test patients exercised at 60 % VO2 max for 30 min . Blood sample s were drawn before , directly after and 30 min after completion of the exercise . Heart rate and lactate increased in all groups ( p<.0001 ) . We furthermore saw significant increases in endocrine parameters ( epinephrine , norepinephrine , ACTH , and beta-endorphin ; all p<.0001 ) in healthy individuals and in MS patients but without a differential effect . Whole-blood stimulated production of IFN-gamma ( IFNgamma ) was induced similarly in all groups ( p<.01 ) . TNF-alpha ( TNFalpha ) and IL-10 were less inducible in MS patients ( trend ) . From these data we could not demonstrate a proinflammatory immune deviation in response to physical stress in MS . The observed trend of hyporesponsive TNFalpha and IL-10 responses in MS warrants further investigation Pulmonary impairments have long been recognized as major causes of morbidity and mortality in individuals with advanced multiple sclerosis ( MS ) . This study was design ed to determine if a 10-week home exercise inspiratory training program in community-dwelling persons with MS improves pulmonary muscle strength and endurance . Forty-six ambulatory individuals with clinical ly diagnosed MS [ Exp and ed Disability Status Scale ( EDSS ) 2.0–6.5 , intervention group mean = 3.96 and control group mean = 3.36 ] were r and omly assigned to an intervention group that received 10 weeks of inspiratory muscle strength training ( IMT ) or a nontreatment control group . Twenty-one subjects in the control group and 20 subjects in the intervention group completed the study . The intervention group demonstrated significantly greater improvement than the control group in maximal inspiratory pressure ( P < 0.001 ) . When compared to the control group , no significant differences were noted for maximal expiratory pressure or maximal ventilation volume after training in the intervention group . Baseline and postexercise training comparison of secondary pulmonary expiratory outcomes were significant in the intervention group for forced expiratory volume at one second ( FEV1 ) ( P = 0.014 ) , forced vital capacity ( FVC ) ( P = 0.041 ) , and midexpiratory flow rate(FEF25–75 % ) ( P = 0.011 ) . No significant changes were noted for the control group . Thus , IMT significantly increased inspiratory muscle strength and result ed in generalized improvements in expiratory pulmonary function in persons with MS who have minimal to moderate disability . Future studies are needed that focus on the long-term effects of IMT with increased resistance and the impact it has on increasing pulmonary function and functional performance Objective : To test the hypothesis that lower extremity progressive resistance training ( PRT ) can improve muscle strength and functional capacity in patients with multiple sclerosis ( MS ) and to evaluate whether the improvements are maintained after the trial . Methods : The present study was a 2-arm , 12-week , r and omized controlled trial including a post study follow-up period of 12 weeks . Thirty-eight moderately impaired patients with MS were r and omized to a PRT exercise group ( n = 19 ) or a control group ( n = 19 ) . The exercise group completed a biweekly 12-week lower extremity PRT program and was afterward encouraged to continue training . After the trial , the control group completed the PRT intervention . Both groups were tested before and after 12 weeks of the trial and at 24 weeks ( follow-up ) , where isometric muscle strength of the knee extensors ( KE MVC ) and functional capacity ( FS ; combined score of 4 tests ) were evaluated . Results : KE MVC and FS improved after 12 weeks of PRT in the exercise group ( KE MVC : 15.7 % [ 95 % confidence interval 4.3–27.0 ] , FS : 21.5 % [ 95 % confidence interval 17.0–26.1 ] ; p < 0.05 ) , and the improvements were better than in the control group ( p < 0.05 ) . The improvements of KE and FS in the exercise group persisted at follow-up after 24 weeks . Also , the exercise effects were reproduced in the control group during the 12-week posttrial PRT period . Conclusions : Twelve weeks of intense progressive resistance training of the lower extremities leads to improvements of muscle strength and functional capacity in patients with multiple sclerosis , the effects persisting after 12 weeks of self-guided physical activity . Level of evidence : The present study provides level III evidence supporting the hypothesis that lower extremity progressive resistance training can improve muscle strength and functional capacity in patients with multiple sclerosis Background : Studies evaluating exercise interventions in people with multiple sclerosis ( PwMS ) demonstrate small to medium positive effects and large variability on a number of outcome measures . No study to date has tried to explain this variability . Objective : This paper presents a novel exploration of data examining the predictors of outcome for PwMS with minimal gait impairment following a r and omised , controlled trial evaluating community-based exercise interventions ( N = 242 ) . Methods : The primary variable was the physical component of the Multiple Sclerosis Impact Scale-29 , version 2 ( MSIS-29 , v2 ) after a 10-week , controlled intervention period . Predictors were identified a priori and were measured at baseline . Multiple linear regression was conducted . Results : Four models are presented lower MSIS-29 , v2 scores after the intervention period were best predicted by a lower baseline MSIS-29,v2 , a lower baseline Modified Fatigue Impact Score ( physical subscale ) , r and omisation to an exercise intervention , a longer baseline walking distance measured by the Six Minute Walk Test and female gender . This model explained 57.4 % of the variance ( F ( 5 , 211 ) = 59.24 , p < 0.01 ) . Conclusion : These results suggest that fatigue and walking distance at baseline contribute significantly to predicting MSIS-29 , v29 ( physical component ) after intervention , and thus should be the focus of intervention and assessment . Exercise is an important contributor to minimising the physical impact of MS , and gender-specific interventions may be warranted Individuals with multiple sclerosis ( MS ) are more sedentary than the general population , increasing their propensity for reduced functional ability , mobility , and activities of daily living . Self-efficacy has been one of the most consistent determinants of physical activity across population s , including those with MS . However , no studies exist that have attempted to influence self-efficacy in MS patients , in an effort to improve physical activity participation . We conducted a three-month r and omised , controlled trial ( n = 26 ) , contrasting the effects of an efficacy-enhancement exercise condition and a control exercise condition on exercise adherence , well-being , and affective responses to exercise . Analyses indicated that individuals in the efficacy enhancement condition attended more exercise sessions , reported greater levels of well-being and exertion , and felt better following exercise than individuals in the st and ard care condition . Regardless of treatment condition , individuals with a stronger sense of exercise self-efficacy , who reported more enjoyment following the exercise sessions , demonstrated significantly greater adherence with the exercise program . We believe this to be the first empirical attempt to change physical activity behavior in persons with MS using a well-established theoretical framework to drive the intervention . Continued examination of self-efficacy as a determinant of behavior change in individuals with MS is needed . Multiple Sclerosis 2007 ; 13 : 652 - 659 . Purpose The aim of this study was to compare the effect of four different programmes on spiroergometric , spirometric and clinical parameters in multiple sclerosis ( MS ) patients . Methods One hundred and twelve MS patients were divided into four groups . The first group underwent neurophysiologically based physiotherapy , the second aerobic training , the third combined therapy ( neurophysiologically based physiotherapy and aerobic training ) and the fourth did not change any habits . Seventeen patients did not finish the study . Patients were examined on impairment ( Exp and ed Disability Status Scale ) , disability ( Barthel Index ) , h and icap ( Environment Status Scale ) , quality of life ( Multiple Sclerosis Quality of Life ) , fatigue ( Modified Fatigue Impact Scale ) , depression ( Beck Depression Inventory Score ) , respiratory function ( spirometric parameters on spirometry ) and physical fitness ( spiroergometric parameters on a bicycle ergometer ) . Results The patients who participated in one of our training programmes showed a significant improvement of the examined parameters in comparison to those who did not change their present habits . Each of the four training programmes had a different impact on the parameters , which means that each of them had a different effect . The neurophysiologically based physiotherapy had the greatest impact on impairment , and the aerobic training on spirometric and spiroergometric parameters . All methods ( the neurophysiologically based physiotherapy , the aerobic training and the combined programme ) had an impact on fatigue Background : Although physical rehabilitation is commonly administered to MS patients , its efficacy has not been established . Objective : We assessed the efficacy of an inpatient physical rehabilitation program on impairment , disability , and quality of life of MS patients with a r and omized , single-blind , controlled trial . Methods : Fifty ambulatory MS patients were assigned to 3 weeks of inpatient physical rehabilitation ( study treatment ) or exercises performed at home ( control treatment ) . Patients were evaluated at baseline and at 3 , 9 , and 15 weeks by a blinded examining physician . Results : No changes in impairment occurred in either group , as measured by the Exp and ed Disability Status Scale . At the end of the intervention the study group improved significantly in disability , as assessed by the Functional Independence Measure ( FIM ) motor domain , compared with controls ( p = 0.004 ) , and the improvement persisted at 9 weeks ( p = 0.001 ) . The effect size statistic was usually large or moderate in all scale scores of the FIM motor domain at 3 weeks and moderate to fair thereafter . The study group also improved in overall health-related quality of life profile compared with controls ; however , the difference was significant only for the mental composite score at 3 ( p = 0.008 ) and 9 weeks ( p = 0.001 ) . Conclusions : Despite unchanging impairment , physical rehabilitation result ed in an improvement in disability and had a positive impact on mental components of health-related quality of life perception at 3 and 9 weeks Purpose : To investigate the effects of a 12‐week home walking program on cardiovascular parameters , fatigue perception , and walking distance in persons with multiple sclerosis ( MS ) . Methods : Fifteen ambulatory persons with MS , not currently participating in exercise were r and omly assigned to control ( C ) or experimental groups ( EX ) . Pretest data collection included resting HR , BP , fatigue perception ( Fatigue Severity Scale ) , and 6‐minute walk test . EX received a home walking program ( 30 min , 3 x week , x 12 weeks ) , using a modification of Karvonen 's formula to calculate HR range . A HR monitor was used to adjust walking speed . The C group refrained from any regular exercise . Posttest data were collected at week 12 and analyzed using the Mann‐Whitney U Test . Results : No statistically significant differences were noted between groups in any measured parameters ; however , walking distance and Physiologic Cost Index did improve in the exercise group . Conclusion : No adverse events or increase in fatigue levels related to the exercise intervention were reported in this study . This home walking program may not be of sufficient intensity to elicit significant cardiovascular changes . Abnormal cardiac responses have been documented in this population , which may have affected the results . Clinicians may need to use alternate measures to assess fitness in this population OBJECTIVE To evaluate the contribution of respiratory muscle weakness ( part 1 ) and respiratory muscle training ( part 2 ) to pulmonary function , cough efficacy , and functional status in patients with advanced multiple sclerosis ( MS ) . DESIGN Survey ( part 1 ) and r and omized controlled trial ( part 2 ) . SETTING Rehabilitation center for MS . PATIENTS Twenty-eight bedridden or wheelchair-bound MS patients ( part 1 ) ; 18 patients were r and omly assigned to a training group ( n = 9 ) or a control group ( n = 9 ) ( part 2 ) . INTERVENTION The training group ( part 2 ) performed three series of 15 contractions against an expiratory resistance ( 60 % maximum expiratory pressure [ PEmax ] ) two times a day , whereas the control group performed breathing exercises to enhance maximal inspirations . MAIN OUTCOME MEASURES Forced vital capacity ( FVC ) , inspiratory , and expiratory muscle strength ( PImax and PEmax ) , neck flexion force ( NFF ) , cough efficacy by means of the Pulmonary Index ( PI ) , and functional status by means of the Extended Disability Status Scale ( EDSS ) . RESULTS Part 1 revealed a significantly reduced FVC ( 43 % + /- 26 % predicted ) , PEmax ( 18 % + /- 8 % predicted ) , and PImax ( 27 % + /- 11 % predicted ) , whereas NFF was only mildly reduced ( 93 % + /- 26 % predicted ) . The PI ( median score , 10 ) and EDSS ( median score , 8.5 ) were severely reduced . PEmax was significantly correlated to FVC , EDSS , and PI ( r = .77 , -.79 , and -.47 , respectively ) . In stepwise multiple regression analysis . PEmax was the only factor contributing to the explained variance in FVC ( R2 = .60 ) , whereas body weight ( R2 = .41 ) was the only factor for the PI . In part 2 , changes in PImax and PEmax tended to be higher in the training group ( p = .06 and p = .07 , respectively ) . The PI was significantly improved after 3 months of training compared with the control group ( p < .05 ) . After 6 months , the PI remained significantly better in the training group . CONCLUSIONS Expiratory muscle strength was significantly reduced and related to FVC , cough efficacy , and functional status . Expiratory muscle training tended to enhance inspiratory and expiratory muscle strength . In addition , subjectively and objective ly rated cough efficacy improved significantly and lasted for 3 months after training cessation Objective : To evaluate the effects of balance retraining in a sample of people with multiple sclerosis . Design : R and omized controlled trial . Setting : Rehabilitation unit . Subjects : A consecutive sample of 44 subjects was r and omized into two experimental groups and one control group . The inclusion criteria were : ability to st and independently more than 30 seconds , ability to walk for 6 m. Interventions : Group 1 received balance rehabilitation to improve motor and sensory strategies . Group 2 received balance rehabilitation to improve motor strategy . Group 3 received treatments not specifically aim ed at improving balance . Main outcome measure : Berg Balance Scale , Dynamic Gait Index and fall frequency were used to assess balance impairments . Dizziness H and icap Inventory and Activities-specific Balance Confidence were used to assess h and icap and the level of balance confidence . Results : Frequency of falls post treatment was statistically different among groups ( P = 0.0001 ) ; The Berg Balance Scale showed an overall statistically significant difference ( P = 0.0008 ) among groups . Change pre — post scores were 6.7 , 4.6 and 0.8 points for groups 1 , 2 and 3 . Dynamic Gait Index showed an overall near statistically significant difference among groups ( P = 0.14 ) , with change pre — post scores of 3.85 , 1.6 and 1.75 points for groups 1 , 2 and 3 ; after the exclusion of drop-outs a statistically significant difference was observed ( P = 0.04 ) . The self-administered tests ( Activities-specific Balance Confidence and Dizziness H and icap Inventory ) did not show clinical ly relevant improvements . Conclusions : Balance rehabilitation appeared to be a useful tool in reducing the fall rate and improving balance skills in subjects with multiple sclerosis . Exercises in different sensory context s may have an impact in improving dynamic balance The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials Objective : To determine the effectiveness of group exercise training on balance , functional status , spasticity , fatigue and quality of life in patients with multiple sclerosis . Design : A r and omized single-blind controlled study . Setting : University hospital , outpatient physical therapy department . Subjects : Ambulatory patients with multiple sclerosis . Interventions : Exercise group completed a 12-week group exercise programme under the physical therapists ’ supervision . Control group was included in the waiting list . Main measures : The primary outcome measures were the Berg Balance Scale , 10-metre walk test , 10-steps climbing test and secondary outcome measures were the Modified Ashworth Scale , Fatigue Severity Scale and Multiple Sclerosis International Quality of Life . Results : Ninety-nine patients completed the study . There were statistically significant improvements for all outcome measures in the group exercise group ( n = 51 ) ( p < 0.01 ) . In the control group ( n = 48 ) , there were statistically significant negative change in the Berg Balance Scale and 10-metre walk test measures ( p = 0.002 , p = 0.001 ) and statistically significant increment only in the Fatigue Severity Scale score ( p = 0.002 ) . The Berg Balance Scale score was increased 4.33 in the exercise group , while a decreased of 2.33 in control group . The 10-metre walk test duration ( second ) was decreased 2.72 in exercise group , while increased 1.44 in control group . In comparing inter-groups changes , both primary and secondary outcome mesures showed significant improvements in favour of the exercise group after the training ( p < 0.05 ) . Conclusion : The study demonstrated that supervised group exercise training is effective in improving balance , functional status , spasticity , fatigue and quality of life in moderately affected people with multiple sclerosis , with no worsening of their clinical status Fatigue occurs in the majority of multiple sclerosis patients and therapeutic possibilities are few . Fatigue , mood and quality of life were studied in patients with multiple sclerosis following progressive resistance training leading to improvement of muscular strength and functional capacity . Fatigue ( Fatigue Severity Scale , FSS ) , mood ( Major Depression Inventory , MDI ) and quality of life ( physical and mental component scores , PCS and MCS , of SF36 ) were scored at start , end and follow-up of a r and omized controlled clinical trial of 12 weeks of progressive resistance training in moderately disabled ( Exp and ed Disability Status Scale , EDSS : 3—5.5 ) multiple sclerosis patients including a Control group ( n = 15 ) and an Exercise group ( n = 16 ) . Fatigue ( FSS > 4 ) was present in all patients . Scores of FSS , MDI , PCS — SF36 and MCS — SF36 were comparable at start of study in the two groups . Fatigue improved during exercise by —0.6 ( 95 % confidence interval ( CI ) —1.4 to 0.4 ) a.u . vs. 0.1 ( 95 % CI —0.4 to 0.6 ) a.u . in controls ( p = 0.04 ) , mood improved by —2.4 ( 95 % CI —4.1 to 0.7 ) a.u . vs. 1.1 ( —1.2 to 3.4 ) a.u . in controls ( p = 0.01 ) and quality of life ( PCS — SF36 ) improved by 3.5 ( 95 % CI 1.4—5.7 ) a.u . vs. —1.0 ( 95 % CI —3.4—1.4 ) a.u . in controls ( p = 0.01 ) . The beneficial effect of progressive resistance training on all scores was maintained at follow-up after further 12 weeks . Fatigue , mood and quality of life all improved following progressive resistance training , the beneficial effect being maintained for at least 12 weeks after end of intervention This study tested whether upper-body endurance training ( ET ) is feasible and can be performed at sufficient intensity to induce cardiovascular adaptations in severely disabled patients with progressive multiple sclerosis ( MS ) . Eleven progressive MS patients ( 6.5 ≤ EDSS ≤ 8.0 ) scheduled for a four-week inpatient rehabilitation program were r and omized to a control group ( CON , n = 5 ) that received st and ard individualized MS rehabilitation or an intervention group ( EXE , n = 6 ) that in addition received 10 sessions of predominantly upper-body ET . One patient dropped out of the EXE group ( drop-out rate : 1/6~17 % ) and no adverse events were recorded . The EXE group completed on average 9.3±0.8 sessions ( ~96.0±5 % ) . During the ET sessions an average heart rate of 93.9±9.3beats*min–1 were sustained corresponding to 91.6±6.8 % of the maximal pre-intervention heart rate . In the EXE group a trend toward a time*group interaction was seen for VO2peak ( p = 0.06 ) . ET is feasible in severely disabled patients with progressive MS and it can probably be performed at sufficient intensity to induce cardiovascular adaptations |
738 | 20,614,457 | There is not enough evidence available to support or refute the effectiveness of combined psychological therapy and pharmacotherapy compared to either of these interventions alone . | BACKGROUND PTSD is an anxiety disorder related to exposure to a severe psychological trauma .
Symptoms include re-experiencing the event , avoidance and arousal as well as distress and impairment result ing from these symptoms .
Guidelines suggest a combination of both psychological therapy and pharmacotherapy may enhance treatment response , especially in those with more severe PTSD or in those who have not responded to either intervention alone .
OBJECTIVES To assess whether the combination of psychological therapy and pharmacotherapy provides a more efficacious treatment for PTSD than either of these interventions delivered separately . | OBJECTIVE Little is known about the efficacy of " next step " strategies for patients with post-traumatic stress disorder ( PTSD ) who remain symptomatic despite treatment . This study prospect ively examines the relative efficacy of augmentation of continued prolonged exposure therapy ( PE ) with paroxetine CR versus placebo for individuals remaining symptomatic despite a course of PE . METHOD Adult out patients meeting DSM-IV criteria for PTSD were recruited from February 2003 to September 2005 at 4 academic centers . Phase I consisted of 8 sessions of individual PE over a 4- to 6-week period . Participants who remained symptomatic , defined as a score of > or= 6 on the Short PTSD Rating Interview ( SPRINT ) and a Clinical Global Impressions-Severity of Illness scale ( CGI-S ) score > or= 3 , were r and omly assigned to the addition of paroxetine CR or matched placebo to an additional 5 sessions of PE ( Phase II ) . RESULTS Consistent with prior studies , the 44 Phase I completers improved significantly with initial PE ( SPRINT : paired t = 7.6 , df = 41 , p < .0001 ; CGI-S : paired t = 6.37 , df = 41 , p < .0001 ) . Counter to our hypothesis , however , we found no additive benefit of augmentation of continued PE with paroxetine CR compared to pill placebo for the 23 r and omly assigned patients , with relatively minimal further gains overall in Phase II . CONCLUSION Although replication with larger sample s is needed before definitive conclusions can be drawn , our data do not support the addition of paroxetine CR compared with placebo to continued PE for individuals with PTSD who remain symptomatic after initial PE , suggesting that the development of novel treatment approaches for PTSD refractory to PE is needed . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00215163 To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results OBJECTIVE To examine the potential benefits of adding a selective serotonin reuptake inhibitor , sertraline , versus placebo , to trauma-focused cognitive-behavioral therapy ( TF-CBT ) for improving posttraumatic stress disorder and related psychological symptoms in children who have experienced sexual abuse . METHOD Twenty-four 10- to 17-year-old female children and adolescents and their primary caretakers were r and omly assigned to receive TF-CBT + sertraline or TF-CBT + placebo for 12 weeks . RESULTS Both groups experienced significant improvement in posttraumatic stress disorder and other clinical outcomes from pre- to posttreatment with no significant group x time differences between groups except in Child Global Assessment Scale ratings , which favored the TF-CBT + sertraline group . CONCLUSIONS Only minimal evidence suggests a benefit to adding sertraline to TF-CBT . A drawback of adding sertraline was determining whether TF-CBT or sertraline caused clinical improvement for children with comorbid depression . Current evidence therefore supports an initial trial of TF-CBT or other evidence -supported psychotherapy for most children with PTSD symptoms before adding medication We examined the feasibility , acceptability , and therapeutic efficacy of a culturally adapted cognitive – behavior therapy ( CBT ) for twelve Vietnamese refugees with treatment-resistant posttraumatic stress disorder ( PTSD ) and panic attacks . These patients were treated in two separate cohorts of six with staggered onset of treatment . Repeated measures Group × Time ANOVAs and between-group comparisons indicated significant improvements , with large effect sizes ( Cohen 's d ) for all outcome measures : Harvard Trauma Question naire ( HTQ ; d=2.5 ) ; Anxiety Sensitivity Index ( ASI ; d=4.3 ) ; Hopkins Symptom Checklist-25 ( HSCL-25 ) , anxiety subscale ( d=2.2 ) ; and Hopkins Symptom Checklist-25 , depression subscale ( d=2.0 ) scores . Likewise , the severity of ( culturally related ) headache- and orthostasis-cued panic attacks improved significantly across Background : To date , there have been no studies comparing cognitive behavior therapy ( CBT ) with Rogerian therapy in post-traumatic stress disorder . Method : Sixty out patients with DSM-IV chronic post-traumatic stress disorder were r and omized into two groups for 16 weekly individual sessions of CBT or Rogerian supportive therapy ( ST ) at two centers . No medication was prescribed . Measures included the Post-Traumatic Stress Disorder Checklist Scale ( PCLS ) , the Hamilton Anxiety Scale , Beck Depression Inventory , and Quality of Life . The general criterion of improvement ( GCI ) was a score of less than 44 on the PCLS . Results : Forty-two patients were evaluated at post-test , 38 at week 52 and 25 at week 104 . At post-test , the rate of patients leaving the trial due to worsening or lack of effectiveness was significantly higher in the ST group ( p = 0.004 ) . At this point , no between-group difference was found on the GCI and any of the rating scales . Intent-to-treat analysis found no difference for the GCI , but patients in the CBT group showed greater improvement on the PCLS and Hamilton Anxiety Scale . Naturalistic follow-up showed sustained improvement without between-group differences at weeks 52 and 104 . Conclusions : CBT retained significantly more patients in treatment than ST , but its effects were equivalent to those of ST in the completers . CBT was better in the dimensional intent-to-treat analysis at post-test Abstract This study evaluated the benefits of add-on hypnotherapy in patients with chronic PTSD . Thirty-two PTSD patients treated by SSRI antidepressants and supportive psychotherapy were r and omized to 2 groups : 15 patients in the first group received Zolpidem 10 mg nightly for 14 nights , and 17 patients in the hypnotherapy group were treated by symptom-oriented hypnotherapy , twice-a-week 1.5-hour sessions for 2 weeks . All patients completed the Stanford Hypnotic Susceptibility Scale , Form C , Beck Depression Inventory , Impact of Event Scale , and Visual Subjective Sleep Quality Question naire before and after treatment . There was a significant main effect of the hypnotherapy treatment with PTSD symptoms as measured by the Posttraumatic Disorder Scale . This effect was preserved at follow-up 1 month later . Additional benefits for the hypnotherapy group were decreases in intrusion and avoidance reactions and improvement in all sleep variables assessed The present study was design ed to determine whether augmenting sertraline with prolonged exposure ( PE ) would result in greater improvement than continuation with sertraline alone . Outpatient men and women with chronic PTSD completed 10 weeks of open label sertraline and then were r and omly assigned to five additional weeks of sertraline alone ( n = 31 ) or sertraline plus 10 sessions of twice-weekly PE ( n = 34 ) . Results indicated that sertraline led to a significant reduction in PTSD severity after 10 weeks but was associated with no further reductions after five more weeks . Participants who received PE showed further reduction in PTSD severity . This augmentation effect was observed only for participants who showed a partial response to medication OBJECTIVE The relative short-term efficacy and long-term benefits of pharmacologic versus psychotherapeutic interventions have not been studied for posttraumatic stress disorder ( PTSD ) . This study compared the efficacy of a selective serotonin reup-take inhibitor ( SSRI ) , fluoxetine , with a psychotherapeutic treatment , eye movement desensitization and reprocessing ( EMDR ) , and pill placebo and measured maintenance of treatment gains at 6-month follow-up . METHOD Eighty-eight PTSD subjects diagnosed according to DSM-IV criteria were r and omly assigned to EMDR , fluoxetine , or pill placebo . They received 8 weeks of treatment and were assessed by blind raters posttreatment and at 6-month follow-up . The primary outcome measure was the Clinician-Administered PTSD Scale , DSM-IV version , and the secondary outcome measure was the Beck Depression Inventory-II . The study ran from July 2000 through July 2003 . RESULTS The psychotherapy intervention was more successful than pharmacotherapy in achieving sustained reductions in PTSD and depression symptoms , but this benefit accrued primarily for adult-onset trauma survivors . At 6-month follow-up , 75.0 % of adult-onset versus 33.3 % of child-onset trauma subjects receiving EMDR achieved asymptomatic end-state functioning compared with none in the fluoxetine group . For most childhood-onset trauma patients , neither treatment produced complete symptom remission . CONCLUSIONS This study supports the efficacy of brief EMDR treatment to produce substantial and sustained reduction of PTSD and depression in most victims of adult-onset trauma . It suggests a role for SSRIs as a reliable first-line intervention to achieve moderate symptom relief for adult victims of childhood-onset trauma . Future research should assess the impact of lengthier intervention , combination treatments , and treatment sequencing on the resolution of PTSD in adults with childhood-onset trauma Concentration camp survivors from Bosnia-Herzegovina , now refugees in the Netherl and s , were given early outpatient treatment for posttraumatic stress disorder ( PTSD ) for 6 months . They were tested with the Watson Question naire before entering therapy , after 6 months and 3 years later when a structured interview design ed to obtain information on psychosocial status was administered . Data were analyzed with PCA-STAT 1.1 statistical package . The treatment was effective on a short-term basis with some long-term effects . Elderly people were no more vulnerable to the onset of PTSD than younger ones but were more resistant to therapy . Psychosocial factors had neither protective nor risk value for the development of PTSD in this group The purpose of this experiment was to conduct a dismantling study of cognitive processing therapy in which the full protocol was compared with its constituent components -- cognitive therapy only ( CPT-C ) and written accounts (WA)--for the treatment of posttraumatic stress disorder ( PTSD ) and comorbid symptoms . The intent-to-treat ( ITT ) sample included 150 adult women with PTSD who were r and omized into 1 of the 3 conditions . Each condition consisted of 2 hr of therapy per week for 6 weeks ; blind assessment s were conducted before treatment , 2 weeks following the last session , and 6 months following treatment . Measures of PTSD and depression were collected weekly to examine the course of recovery during treatment as well as before and after treatment . Secondary measures assessed anxiety , anger , shame , guilt , and dysfunctional cognitions . Independent ratings of adherence and competence were also conducted . Analyses with the ITT sample and with study completers indicate that patients in all 3 treatments improved substantially on PTSD and depression , the primary measures , and improved on other indices of adjustment . However , there were significant group differences in symptom reduction during the course of treatment whereby the CPT-C condition reported greater improvement in PTSD than the WA condition There has been growing interest in the concept of resilience and the question as to whether psychotropic medications or psychosocial treatments might have resilience-enhancing effects . This pilot study investigates resilience in a sample of patients with post-traumatic stress disorder ( PTSD ) before and after treatment . Effects of treatment with tiagabine , fluoxetine , sertraline alone , and sertraline with cognitive behavioural therapy on resilience were assessed using the Connor-Davidson Resilience Scale ( CD-RISC ) . Changes in resilience after treatment were measured and response to treatment was predicted from demographic , resilience and baseline disability measures . Changes in resilience following treatment were statistically significant . Items that showed the greatest change related to confidence , control , coping , knowing where to turn for help and adaptability . Items showing the least change related to religious and existential aspects of resiliency , effort , acting on a hunch , decision-making and goals . In linear and logistic regression models , gender , baseline CD-RISC score , baseline Sheehan Disability Scale score and an individual item from the CD-RISC scale , ‘ Sense of Humor ’ , were significant predictors of response to treatment . Treatment of PTSD significantly improved resilience and reduced symptoms in this sample . Further controlled studies are indicated Cambodian refugees with posttraumatic stress disorder ( PTSD ) represent a cohort in severe need of treatment , but little information is available to guide treatment choices . We selected a sample of pharmacotherapy-refractory individuals to test the efficacy of combination treatment with sertraline and cognitive-behavior therapy ( CBT ) for treating PTSD . Participants in this pilot study were ten Khmer-speaking women who had been at a mean age of 22 - 26 years during the Pol Pot period ( 1975 - 1979 ) . These patients were r and omly assigned to either sertraline alone or combined treatment . We found that combined treatment offered additional benefit in the range of medium to large effect sizes for PTSD and associated symptoms . Our findings indicate that substantial gains can be achieved by adding CBT to pharmacotherapy for PTSD , and that a program of CBT emphasizing information , exposure , and cognitive-restructuring can be successfully modified for Khmer-speaking refugees The beta-adrenergic blocker propranolol given within hours of a psychologically traumatic event reduces physiologic responses during subsequent mental imagery of the event . Here we tested the effect of propranolol given after the retrieval of memories of past traumatic events . Subjects with chronic post-traumatic stress disorder described their traumatic event during a script preparation session and then received a one-day dose of propranolol ( n=9 ) or placebo ( n=10 ) , r and omized and double-blind . A week later , they engaged in script-driven mental imagery of their traumatic event while heart rate , skin conductance , and left corrugator electromyogram were measured . Physiologic responses were significantly smaller in the subjects who had received post-reactivation propranolol a week earlier . Propranolol given after reactivation of the memory of a past traumatic event reduces physiologic responding during subsequent mental imagery of the event in a similar manner to propranolol given shortly after the occurrence of a traumatic event |
739 | 31,419,046 | Thus , there was a lack of evidence for physical activity interventions during peri-conception and pregnancy .
Interventions with evidence of efficacy tended to target multiple levels of the SEM , with emphasis on parents , and extend over long periods .
Effective intervention elements for early life obesity prevention included classes on parenting skills , alteration of the kindergarten playground , and financial incentives .
Evidence from low- and middle-income countries was scarce , and evidence for intervention effect on obesity-related NCDs was missing . | null | null |
740 | 30,902,588 | The present meta- analysis demonstrates that speech therapy does not influence the latency and amplitude results of the P300 evoked potential in children undergoing speech therapy intervention | INTRODUCTION The patient 's evolution in the audiology and speech- language clinic acts as a motivator of the therapeutic process , contributing to patient adherence to the treatment and allowing the therapist to review and /or maintain their clinical therapeutic conducts .
Electrophysiological measures , such as the P300 evoked potential , help in the evaluation , underst and ing and monitoring of human communication disorders , thus facilitating the prognosis definition in each case .
OBJECTIVE To determine whether the audiology and speech- language therapy influences the variation of P300 latency and amplitude in patients with speech disorders undergoing speech therapy . | The current study was design ed to explore the use of behavioral ( i.e. , accuracy and reaction times ) and electrophysiological measures ( i.e. , event-related potentials ) to assess the impact of a family-based preventive intervention for preschool-aged , maltreated children in foster care . These measures were recorded during a computerized flanker task design ed to assess cognitive control and response monitoring . The sample was recruited from a larger r and omized efficacy trial of Multidimensional Treatment Foster Care for Preschoolers ( MTFC-P ) and included foster children assigned to the intervention condition ( n = 10 ) , foster children assigned to a services-as-usual comparison condition ( n = 13 ) , and low-income , nonmaltreated community children ( n = 11 ) . The children ’s behavioral and electrophysiological performance on the task was generally consistent with previous research with adults and older children . There were no group differences on the behavioral measures of cognitive control or response monitoring . Notably , however , group differences were observed on the electrophysiological measures of response monitoring . Specifically , the foster children who received services as usual were significantly less responsive to performance feedback about errors than the foster children who received the intervention and the nonmaltreated children . Applications of this methodology and implication s of the results for future prevention research are discussed Children with language processing deficits have various learning impairments and poor scholastic performance . In 3 - 10 % of all children a specific language processing deficit can be identified by the Sound Connecting Sub-Test of the Illinois Test of Psycholinguistic-Abilities ( SC-ITPA ) . These children among which we drew our index group ( AS-Group ) suffer from the disability to recognize isolated sounds as parts of words . Following linguistic terminology this is known as an auditory sequential sound processing deficit ( ASSPD ) Eighteen children ( AS-Group ) and 21 controls ( C-Group ) were subjected to mapped P300 evoked potential analyses of cortical response to acoustic stimulation in the oddball paradigm . The data presented here show that there exists significant relation between the P300 amplitude reduction and ASSPD . The P300 amplitude decrease measured in the AS-Group is due to a reduced information transmission in accordance with Johnson 's Triarchic Model of the P300 Amplitude . The cerebral structures involved in poor language processing are localized at the left temporo-parietal cortex . This supports the hypothesis that the underlying neuronal defect of ASSPD is localized in the language center and not in the auditory pathway . The P300 amplitude may serve as electrophysiological tool to identify ASSPD and to quantify the degree of improvement in the course of specific therapy The magnocellular deficit theory is one of the prominent hypotheses in dyslexia research . However , recent studies have produced conflicting results . Ten dyslexic children and 12 controls were examined with visual evoked potentials elicited by r and om dot kinematogram . The experiment comprises two sequences , one with r and omly moving dots ( control condition ) and a second sequence where a fraction of the dots were moved coherently at the left or right side ( depending on the level of coherence , 10 % , 20 % , and 40 % of the dots ) . R and omly moving dots elicited two components , a P100 and P200 , which were not different between the groups . Coherently moving dots elicited a late positivity between 300 and 800 ms , which was significantly attenuated in dyslexic children . The area of this component becomes larger at a higher level of coherence . This study supports the hypothesis of an impairment of a specific magnocellular function in dyslexia PURPOSE To verify the effectiveness of the Cognitive Auditory Evoked Potential-P300 ( CAEP-P300 ) for monitoring the therapeutical evolution of students with developmental dyslexia . METHODS Twenty students diagnosed with developmental dyslexia , of both genders , aged between 8 and 14 years , divided into two r and omized groups , one of them su bmi tted to a phonological remediation program associated with reading and writing ( GI ) , and the other one representing the control group ( GII ) , participated in the study . The groups were paired up , and the individuals were su bmi tted to two evaluations of the CAEP-P300 and the same interval was kept for both . Paired Student 's t-test , ANOVA test , and Pearson 's correlation coefficient were used , adopting 5 % significance level . RESULTS The statistical comparison of the pre and post evaluations of each group demonstrated difference in the Phonological Awareness Test ( p=0.000 ) and in the P300 latency ( p=0.005 ) only for GI . CONCLUSION CAEP-P300 use for monitoring the therapeutical evolution of children with developmental dyslexia is possible and represents a viable option for intervention programs PURPOSE To evaluate whether a hypothesis suggesting that apraxia of speech results from phonological overspecification could be relevant for childhood apraxia of speech ( CAS ) . METHOD High-density EEG was recorded from 5 children with CAS and 5 matched controls , ages 5 - 8 years , with and without CAS , as they listened to r and omized sequences of CV syllables in two oddball paradigms : phonemic ( /ba/ , /pa/ ) and allophonic ( /pa/ , /p(h)a/ ) . RESULTS In the phonemic contrast condition , mismatch negativity ( MMN ) responses to oddball sounds were observed for the typically developing ( comparison ) group but not the CAS group , although a component similar to an immature mismatch response was apparent . The allophonic contrast did not elicit MMN responses in the comparison group , but in the CAS group , an MMN-like response was observed . CONCLUSION The authors propose that these preliminary findings are consistent with a view of CAS as a disorder that not only affects motor planning but also has a phonological component |
741 | 30,993,513 | Conclusions This systematic review of staple-line leaks following LSG demonstrated a significantly lower rate using APM staple-line reinforcement as compared to oversewing , use of sealants , BPS reinforcement , or no reinforcement .
Variation in surgical technique may also contribute to leak rates | Background Staple-line leaks following laparoscopic sleeve gastrectomy ( LSG ) remain a concerning complication .
Staple-line buttressing is largely adopted as an acceptable reinforcement but data regarding leaks have been equivocal .
This study compared staple-line leaks in five reinforcement options during LSG : no reinforcement ( NO-SLR ) , oversewing ( suture ) , nonabsorbable bovine pericardial strips ( BPS ) , tissue sealant or fibrin glue ( Seal ) , or absorbable polymer membrane ( APM ) . | INTRODUCTION The South Pacific has a high prevalence of obesity and super-obesity . We review ed our experience with laparoscopic sleeve gastrectomy ( LSG ) to evaluate its efficacy and safety . METHODS A retrospective review of a prospect ively collected data base of LSGs carried out by one surgeon in one center . The percentage of excess weight loss and the rate of resolution or improvement of comorbidities reflected efficacy , and major complications or mortalities reflected safety . RESULTS From January 2008 to February 2013 , we performed 510 surgeries and included 494 consecutive patients ( 367 females ) ( 45.5 ± 11.2 years ) in our study . LSG was the primary procedure in 384 patients , 6 patients had redo bariatric surgery after failure of initial LSG , 57 patients had a history of gastric b and ing with insufficient weight loss or b and -related complications , and 46 super-obese patients had an intragastric balloon placed before LSG . Average starting body mass index was 47.8 kg m(-2 ) . Mean percent excess weight loss was 64.3 % at 1 year ; 67.3 % at 2 years and 66.4 % at 3 years . The percentages of resolved comorbidities were as follows : hypertension : 48.3 % , type 2 diabetes mellitus : 72.5 % , dyslipidemia : 61.0 % , and obstructive sleep apnea : 77.8 % . The mortality rate was 1/494 . The postoperative morbidity included gastric fistula in 3.0 % , hemorrhaging in 2.4 % , and postoperative gastroesophageal reflux in 9.4 % . CONCLUSIONS In the South Pacific , LSG is a safe and effective means of treating morbid obesity with sustained weight loss and resolution of comorbid medical conditions Background Laparoscopic sleeve gastrectomy ( LSG ) is emerging as a popular “ st and -alone ” bariatric procedure . We report our 5 years experience with LSG as a single-stage bariatric procedure with which to study the technical progress , learning curve , complications , and follow-up results . Methods Prospect ively collected data of 228 patients ( 145 females and 83 males ) , who underwent LSG for morbid obesity , from February 2007 to March 2012 , was retrospectively analyzed . Results The mean age was 34.68 years ( range , 18–62 years ) and the mean preoperative body mass index ( BMI ) was 37.42 ± 4.75 kg/m2 ( range , 32.08–65.69 kg/m2 ) . Mean operative time was 60.63 ± 27.37 min . The mean BMI decreased to 26.15 ± 3.71 kg/m2 at 3 years ( p < 0.001 ) and to 27.94 ± 4.08 kg/m2 at 5 years ( p < 0.001 ) . Mean percentage excess weight loss was 71.96 ± 21.30 % at 3 years and 63.71 ± 20.08 % at 5 years . The 30-day readmission rate was 3.07 % .Overall complication rate was 4.3 % , including strictures , leaks , peritonitis , gastrocutaneous fistula , and one ( 0.43 % ) mortality . One patient with weight regain and another with stricture underwent conversion to Roux-en-Y gastric bypass . Complication rates significantly decreased after the first 50 cases ( p = 0.022 ) , suggesting an initial learning curve . Resolution of diabetes , hypertension , and hyperlipidemia was 66.67 , 100 , and 50 % , respectively , at 5 years . Conclusions LSG as a single-stage bariatric procedure is safe and durable , achieving weight loss and resolution of comorbidities up to 5 years . Adherence to technical details is pivotal in reducing complications associated with the initial learning phase BACKGROUND Bariatric surgery is considered as being contraindicated for morbidly obese patients who also have inflammatory bowel disease ( IBD ) . The aim of our study was to report the outcomes of bariatric surgery in morbidly obese IBD patients . METHODS The prospect ively collected data of all the patients diagnosed as having IBD who underwent bariatric operations in 2 medical centers between October 2006 and January 2014 were retrieved and analyzed . RESULTS One male and 9 female morbidly obese IBD patients ( 8 with Crohn 's disease and 2 with ulcerative colitis ) underwent bariatric surgery . Their mean age was 40 years , and their mean body mass index was 42.6 kg/m2 . Nine of them underwent a laparoscopic sleeve gastrectomy and 1 underwent a laparoscopic adjustable gastric b and . Eight patients had obesity-related co-morbidities , including type 2 diabetes , hypertension , sleep apnea , osteoarthropathy , etc . After a median follow-up of 46 months ( range 9 - 67 ) , all of the patients lost weight , with an excess weight loss of 71 % , and 10 out of 16 obesity-related co-morbidities were resolved . There was 1 complication not related to IBD , and no IBD exacerbation . CONCLUSION Bariatric surgery was safe and effective in our morbidly obese IBD patients . The surgical outcome in this selected patient group was similar to that of comparable non-IBD patients Introduction : Laparoscopic sleeve gastrectomy ( LSG ) is gaining acceptance as a st and -alone bariatric procedure with proven efficacy on weight loss and obesity-related comorbidities . A specific and potentially severe complication of LSG is the staple line leak ( SLL ) . Our aim was to report the SLL rate and its management in a prospect i ve cohort of 378 LSGs . Patients and Methods : A total of 378 patients underwent LSG from July 2005 to July 2011 . The gastric transection was performed by an initial 60 mm firing of 4.5 mm staples at the antrum and successive 60 mm firings of 3.5 mm staples at the gastric body and fundus toward the left diaphragmatic crus . A 36 Fr bougie was used to calibrate the gastric tube . The staple line was systematic ally reinforced with a partial-thickness running suture . Results : The overall complications and SLL rate were 20/378 ( 5.29 % ) and 9/378 ( 2.38 % ) , respectively . SLLs were managed by laparoscopic ( n=2 ) or open ( n=1 ) exploration , drainage and endoscopic self-exp and able covered stent , computed tomography – guided percutaneous drainage ( n=2 ) , or a self-exp and able covered stent alone ( n=4 ) . Medical support including total parenteral nutrition and adapted antibiotics was started in all patients . The combined treatment modalities were successful in all cases . Conclusions : SLL was the most common complication of LSG accounting for half of the overall complications . Percutaneous drainage and self-covered stents combined with antibiotics and parenteral nutrition are effective for SLL and should be proposed as first-line treatment in stable patients Background Single incision laparoscopy remains controversial due to technical challenges which may cause suboptimal outcomes . This study aims to evaluate the feasibility and equivalency of the single incision sleeve gastrectomy ( SISG ) when compared to the traditional multiport sleeve gastrectomy ( MPSG ) approach in a matched cohort evaluating technical aspects and postoperative results . Methods This is a retrospective analysis of prospect ively collected data in a consecutive cohort of 113 SG ( MPSG = 77 , SISG = 36 ) . The 36 patients who underwent SISG were included as the case group . Thirty-six MPSG patients were included in the control group , in 1:1 ratio with cases after matching for BMI , age , race , gender , and additional demographic data . Operative time ( OT ) in minutes and length of stay ( LOS ) in days was measured and excess weight loss ( EWL ) at 6 months and 1 year was collected and evaluated . Results Mean BMI was equivalent ( SISG 43.06 , MPSG 43.72 , p = 0.36 ) . Mean OT for the SISG was 116.78 and 118.25 for the MPSG ( p = 0.84 ) , and mean LOS was 1.80 for the SISG and 1.75 for the MSPG ( p = 0.75 ) . EWL at 6 months was 58.4 % for the SISG and 58.5 % for the MPSG ( p = 0.98 ) and 72.3 and 74.1 % ( p = 0.77 ) for 1 year , respectively . There were no leaks in either group . There was one reoperation for postoperative bleeding in the MPSG group . Conclusions Sleeve gastrectomy can be performed safely using single incision techniques with equivalent outcomes for weight loss Background One of the most serious complications after laparoscopic sleeve gastrectomy ( LSG ) is gastric leak . Few publications exist concerning the treatment of gastric leak . We sought to determine by way of a prospect i ve study the clinical presentation , postoperative course , and treatment of gastric leak after LSG for obesity . Methods From October 2005 to August 2008 , 214 patients with different degrees of obesity underwent LSG . During surgery , each patient received saline with methylene blue by way of nasogastric tube and had a drain placed . All patients underwent radiologic study with liquid barium sulphate on postoperative day 3 . Results Seven patients developed gastric leak . Leak in two patients ( 28.6 % ) was diagnosed by upper gastrointestinal tract ( UGI ) study . Two patients had type I leak ( 28.6 % ) , and five patients had type II leak ( 71.4 % ) . Four patients underwent reoperation . Three patients were managed medically with enteral or parenteral feeding ; the drain was maintained in situ ; and collection s were drained by percutaneous punctions guided by computed axial tomography . Mean hospital length of stay was 28.8 days , and time to leakage closure was 43 days after surgery . Conclusion Different ways exist to manage gastric leak , depending on the magnitude of the collection and the clinical repercussions . When treatment necessitates reintervention and is performed early , suture repair is more likely to be successful . Leakage closure time will vary Background Bariatric operations mostly combine a restrictive gastric component with a rerouting of the intestinal passage . The pylorus can thereby be alternatively preserved or excluded . With the aim of performing a “ pylorus-preserving gastric bypass ” , we present early results of a proximal postpyloric loop duodeno-jejunostomy associated with a sleeve gastrectomy ( LSG ) compared to results of a parallel , but distal LSG with a loop duodeno-ileostomy as a two-step procedure . Methods 16 patients underwent either a two-step LSG with a distal loop duodeno-ileostomy ( DIOS ) as revisional bariatric surgery or a combined single step operation with a proximal duodeno-jejunostomy ( DJOS ) . Total small intestinal length was determined to account for inter-individual differences . Results Mean operative time for the second-step of the DIOS operation was 121 min and 147 min for the combined DJOS operation . The overall intestinal length was 750.8 cm ( range 600 - 900 cm ) with a bypassed limb length of 235.7 cm in DJOS patients . The mean length of the common channel in DIOS patients measured 245.6 cm . Overall excess weight loss ( % EWL ) of the two-step DIOS procedure came to 38.31 % and 49.60 % , DJOS patients experienced an % EWL of 19.75 % and 46.53 % at 1 and 6 months , resp . No complication related to the duodeno-enterostomy occurred . Conclusions Loop duodeno-enterosomies with sleeve gastrectomy can be safely performed and may open new alternatives in bariatric surgery with the possibility for inter-individual adaptation Background To evaluate changes in obesity-related diseases and micronutrients after laparoscopic sleeve gastrectomy ( LSG ) . Methods We started the procedure in May 2007 , and by December 2011 , 117 patients could be evaluated for a two year follow-up . Comparisons of preoperative status with 12 and 24 months postoperative status were made for body mass index ( BMI ) , obesity-related diseases and micronutrients . Results Major complications included bleeding requiring transfusion at 5.1 % , leak at 1.7 % and abscess without a visible leak at 0.9 % . Mean BMI was reduced from 46.6 ( st and ard deviation ( SD ) 6.0 ) kg/m2 to 30.6 ( SD 5.6 ) kg/m2 at two years , and resolution occurred for 80.7 % of patients with type 2 diabetes , 63.9 % with hypertension , 75.8 % with hyperlipidemia , 93.0 % with sleep apnea , 31.4 % with musculoskeletal pain , 85.4 % with snoring and 73.3 % with urinary incontinence . Amenorrhea resolved in all premenopausal females . The proportion of patients with symptomatic gastroesophageal reflux disease increased from 12.8 % to 27.4 % . The prevalence of patients with low ferritin-levels increased , while 25-hydroxyvitamin D ( 25(OH)D ) deficiency decreased postoperatively . Conclusions LSG is an effective procedure for morbid obesity and obesity-related diseases , but the technique should be further explored particularly to avoid gastroesophageal reflux Introduction Laparoscopic sleeve gastrectomy ( LSG ) is a bariatric procedure with very good long-term weight-reducing and metabolic effects . Aim Here we report 6 years ’ experience with LSG performed in morbidly obese patients by one surgical team focusing on the impact of the degree of sleeve restriction and safety of the procedure without over-sewing the staple line . Material and methods From 2006 to 2012 , 207 morbid obese patients with average age of 43.4 years and average body mass index 44.9 kg/m2 underwent LSG without over-sewing the staple line . The complete 5- and 3-year follow-up is recorded in 59 and 117 patients with prospect i ve data collection at 3 , 6 , 9 , 12 , 18 , 24 , 36 , 42 and 60 months after LSG . Group 1 patients operated in 2006–2008 had smaller sleeve restriction . Group 2 patients operated in 2009–2012 had major sleeve restriction . All procedures were performed without over-sewing of the staple line . Results The average % E BMI L ( excess body mass index loss ) in group 1 patients with minor sleeve restriction reached 54.1 % and average % EWL ( excess weight loss ) was 50.8 % while in group 2 with major sleeve restriction the average % E BMI L reached 69.7 % and average % EWL was 66.8 % . Final weight reduction was significantly higher in group 2 patients compared to group 1 patients with smaller sleeve restriction . Out of 49 patients with preoperatively diagnosed T2DM ( type 2 diabetes mellitus ) was completely resolved in 70.8 % . Pre-operatively diagnosed hypertension normalized in 64.2 % , improved in 23.2 % , and remained unchanged in 12.6 % of patients . Conclusions Carefully performed LSG without over-sewing the staple line is feasible and safe . A better weight-reducing effect was present in patients with major sleeve restriction Background Leaks after sleeve gastrectomy ( SG ) may be due to a mismatch between staple height and tissue thickness . The aim of this study was to determine the range of gastric thicknesses in three areas of stapling . Methods SG was performed using a 40-Fr suction calibration system 4 cm from the pylorus . Measurement of combined gastric walls was accomplished with an applied pressure of 8 g/mm2 on the fundus , midbody , and antrum . Results We enrolled 26 SG patients ( 15 women , 11 men ; mean age 36.8 years ) . Body mass index ( BMI ) averaged 45.3 kg/m2 overall , 44.7 kg/m2 for males and 45.7 kg/m2 for females . Although male patients had a thicker stomach antrum than female patients ( 3.12 vs. 3.09 mm ) , the midbody ( 2.57 vs. 3.09 mm ) and proximal areas ( 1.67 vs. 1.72 mm ) were thicker in female patients . However , some maximum fundus thicknesses were up to 2.83 mm in females and 2.28 mm in males . Some antra were as thick as 4.07 mm in females and 5.39 mm in males . Also , men had a longer average staple line ( 22.95 vs. 19.90 cm ) . Conclusion Because of the range of gastric thicknesses , a single staple height can not be used to appose the full range of gastric wall thicknesses without potentially causing necrosis or poor apposition . To help avoid leaks , a thickness calibration device is needed to determine correct staple height Introduction Laparoscopic sleeve gastrectomy ( LSG ) is now a popular bariatric procedure worldwide with rising prevalence over the last decade . Staple line leak and bleeding are the most dangerous complications of LSG . Staple line reinforcement ( SLR ) by oversewing the staple line was suggested to reduce the incidence of leak and bleeding . We design ed a r and omized controlled prospect i ve study to investigate the value of SLR by invaginating the whole staple line using unidirectional absorbable 3/0 V-Loc 180 sutures ( Covidien , Mansfield , MA , USA ) to no SLR in LSG . Patients and Methods Nine hundred and twenty patients undergoing LSG between March 2016 and March 2017 were included in the study ; they were prospect ively r and omized into two groups : A and B , each of 460 patients . In group A , the entire staple line was invaginated with continuous seromuscular suturing using 3/0 V-Loc 180 suture ( Covidien , Mansfield , MA , USA ) , and in group B , no reinforcement was done . The patients were selected according to National Institute of Health ( NIH ) guidelines . All procedures were performed by the same team of experienced bariatric surgeons . Patients were followed up for 6 weeks after surgery for occurrence of complications . Results The two groups were matched considering the demographic data . Operative time was significantly longer in group A ( P = 0.001 ) , with mean operative time in group A was 69 min , while that in Group B was 50.8 min . Leak occurred in eight cases ( 1.7 % ) in group B and none ( 0 % ) in group A ; leak was significantly lower in group A ( P = 0.008 ) . Bleeding occurred in two patients ( 0.4 % ) in group A and in seven ( 1.5 % ) in group B ( P = 0.178 ) , with no statistically significant difference between both groups as regards bleeding . Conclusion Comparing SLR by invaginating the whole staple line using unidirectional absorbable 3/0 V-Loc 180 sutures ( Covidien , Mansfield , MA , USA ) to no SLR in a relatively large cohort of patients undergoing LSG , in a r and omized controlled prospect i ve study , has proved statistically significant value for SLR by invaginating sutures BACKGROUND Laparoscopic sleeve gastrectomy ( LSG ) has become popular due to its technical ease and excellent short-term results . Underst and ing the risk profile of LSG compared with the gold st and ard laparoscopic Roux-en-Y gastric bypass ( LRYGB ) is critical for patient selection . OBJECTIVES To use traditional regression techniques and r and om forest classification algorithms to compare LSG with LRYGB using the 2015 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Data Registry . SETTING United States . METHODS Outcomes were leak , morbidity , and mortality within 30 days . Variable importance was assessed using r and om forest algorithms . Multivariate models were created in a training set and evaluated on the testing set with receiver operating characteristic curves . The adjusted odds of each outcome were compared . RESULTS Of 134,142 patients , 93,062 ( 69 % ) underwent LSG and 41,080 ( 31 % ) underwent LRYGB . One hundred seventy-eight deaths occurred in 96 ( .1 % ) of LSG patients compared with 82 ( .2 % ) of LRYGB patients ( P<.001 ) . Morbidity occurred in 8 % ( 5.8 % in LSG versus 11.7 % in LRYGB , P<.001 ) . Leaks occurred in 1 % ( .8 % in LSG versus 1.6 % in LRYGB , P<.001 ) . The most important predictors of all outcomes were body mass index , albumin , and age . In the adjusted multivariate models , LRYGB had higher odds of all complications ( leak : odds ratio 2.10 , P<.001 ; morbidity : odds ratio 2.02 , P<.001 ; death : odds ratio 1.64 , P<.01 ) . CONCLUSION In the Metabolic and Bariatric Surgery Accreditation and Quality Improvements data registry for 2015 , LSG had half the risk-adjusted odds of death , serious morbidity , and leak in the first 30 days compared with LRYGB Importance Sleeve gastrectomy is increasingly used in the treatment of morbid obesity , but its long-term outcome vs the st and ard Roux-en-Y gastric bypass procedure is unknown . Objective To determine whether there are differences between sleeve gastrectomy and Roux-en-Y gastric bypass in terms of weight loss , changes in comorbidities , increase in quality of life , and adverse events . Design , Setting , and Participants The Swiss Multicenter Bypass or Sleeve Study ( SM-BOSS ) , a 2-group r and omized trial , was conducted from January 2007 until November 2011 ( last follow-up in March 2017 ) . Of 3971 morbidly obese patients evaluated for bariatric surgery at 4 Swiss bariatric centers , 217 patients were enrolled and r and omly assigned to sleeve gastrectomy or Roux-en-Y gastric bypass with a 5-year follow-up period . Interventions Patients were r and omly assigned to undergo laparoscopic sleeve gastrectomy ( n = 107 ) or laparoscopic Roux-en-Y gastric bypass ( n = 110 ) . Main Outcomes and Measures The primary end point was weight loss , expressed as percentage excess body mass index ( BMI ) loss . Exploratory end points were changes in comorbidities and adverse events . Results Among the 217 patients ( mean age , 45.5 years ; 72 % women ; mean BMI , 43.9 ) 205 ( 94.5 % ) completed the trial . Excess BMI loss was not significantly different at 5 years : for sleeve gastrectomy , 61.1 % , vs Roux-en-Y gastric bypass , 68.3 % ( absolute difference , −7.18 % ; 95 % CI , −14.30 % to −0.06 % ; P = .22 after adjustment for multiple comparisons ) . Gastric reflux remission was observed more frequently after Roux-en-Y gastric bypass ( 60.4 % ) than after sleeve gastrectomy ( 25.0 % ) . Gastric reflux worsened ( more symptoms or increase in therapy ) more often after sleeve gastrectomy ( 31.8 % ) than after Roux-en-Y gastric bypass ( 6.3 % ) . The number of patients with reoperations or interventions was 16/101 ( 15.8 % ) after sleeve gastrectomy and 23/104 ( 22.1 % ) after Roux-en-Y gastric bypass . Conclusions and Relevance Among patients with morbid obesity , there was no significant difference in excess BMI loss between laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass at 5 years of follow-up after surgery . Trial Registration clinical trials.gov Identifier : Background Between 2 and 8 weeks before surgery , most bariatric surgery groups establish strict dietary treatments with a total caloric intake of less than 1,000 kcal/day in order to maximize weight loss during this period of time . Methods A prospect i ve r and omized clinical trial of all the patients undergoing laparoscopic sleeve gastrectomy ( LSG ) was performed . Patients were r and omly assigned into 3 groups : those patients receiving a preoperative regular diet of 900 kcal/day ( group 1 ) , those receiving a preoperative balanced energy high-protein formula ( group 2 ) and those receiving preoperative Immunonutrition ( group 3 ) . Preoperative weight loss , postoperative pain , complications and analytical acute phase reactants were investigated . Results Sixty patients were included in the study , 20 in each group . Preoperative excess weight loss was 7.7 % in group 1 , 12.3 % in group 2 and 15.3 % in group 3 ( p = 0.014 ) . Median postoperative pain was 3.5 in group 1 , 3 in group 2 and 2 in group 3 ( p = 0.048 ) . C-reactive protein determined 24 h after surgery was significantly lower in group 3 than in the other groups . AST and ALT values were significantly lower in group 3 than in the other groups , without significant differences between groups 1 and 2 . Conclusions Preoperative diet with Immunonutrition formulas during 2 weeks achieves a greater preoperative weight loss , lower postoperative pain and lower values of CRP and liver enzymes than high-protein formulas or regular diet , all of them with similar caloric intake Background The combination of pneumoperitoneum and intraoperative retraction of the left lobe of the liver leads to hepatocellular injury during laparoscopic gastric surgery . Fatty livers are more susceptible to ischaemic insults . This trial investigated whether the antioxidant N-acetylcysteine ( NAC ) reduced liver injury during laparoscopic sleeve gastrectomy ( LSG ) . Methods Patients undergoing LSG were r and omised ( single blinded ) to receive intraoperative NAC infusion or st and ard anaesthetic treatment . Blood sample s were taken before and after surgery ( days 0 to 4 ) . Primary endpoints included serum aminotransferases . Secondary measures were C-reactive protein , weight cell count ( WCC ) , cytokines ( interleukin 6 and 10 ) and cytokeratin-18 as markers of apoptosis . Intraoperative liver biopsy sample s were assessed using a locally developed injury score . Results Twenty patients ( 14 females , mean age 44.5 ( SEM ± 2.9 ) years , mean BMI 60.8 ( SEM ± 2.4 ) kg/m2 ) were recruited ( NAC n = 10 , control n = 10 ) . The trial was stopped early after a planned interim analysis . Baseline liver function was similar . The peak rise in liver enzymes was on day 1 , but levels were not significantly different between the groups . Rates of complications and length of stay were not significantly different . Secondary outcome measures , including white cell count ( WCC ) , cytokines and cytokeratin (CK)-18 fragments , were not different between groups . Liver injury scores did not differ significantly . Conclusions NAC did not reduce intraoperative liver injury in this small number of patients . The heterogenous nature of the study population , with differences in co-morbidities , body mass index and intraabdominal anatomy , leads to a varied post-operative inflammatory response . Significant hepatocyte injury occurs through both necrosis and apoptosis Background Laparoscopic sleeve gastrectomy ( LSG ) is considered a primary bariatric surgery and is increasingly being performed worldwide ; however , long-term data regarding the durability of this procedure are inadequate . Here , we report the long-term results of LSGs in comparison to those of gastric bypass surgeries . Methods A prospect ively collected bariatric data base from Ming-Shen General Hospital was retrospectively studied . Five hundred nineteen morbidly obese patients ( mean age 36.0 ± 9.1 years old ( 14–71 ) , 74.6 % female , mean body mass index ( BMI ) 37.5 ± 6.1 kg/m2 ) underwent LSG as a primary bariatric procedure from 2006 to 2012 at our institute . The operative parameters , weight loss , laboratory data , and quality of life were followed . Another two matched groups of laparoscopic Roux-en-Y gastric bypass ( RYGB ) and laparoscopic single anastomosis ( mini- ) gastric bypass ( SAGB ) patients who were matched in terms of age , sex , and BMI were recruited for comparisons . Results The mean surgical time for LSG was 113.5 ± 31.3 min , and the mean blood loss was 49.1 + 100.9 ml . The rate of major complications was 1.6 % , and the average length of the postoperative stay was 3.0 ± 1.7 days . The operation times of the RYGB patients were longer than those of both the LSG and SAGB patients . The RYGB and SAGB patients experienced higher major complication rate than the LSG patients . The weight loss of the LSG patient at 5 years was 28.3 + 8.9 % , and the mean BMI was 27.1 + 4.3 . The RYGB patients exhibited a 5-year weight loss similar to the LSG patients , and the SAGB patients exhibited greater weight loss than both of the other groups . Both the RYGB and SAGB patients exhibited significantly better glycemic control and lower blood lipids than the LSG patients , but the LSG patients exhibited a lesser micronutrient deficiency than the RYGB and SAGB groups . All three of the groups exhibited improved quality of life at 5 years after surgery , and there was no significant between-group difference in this measure . Conclusions LSG appears to be an ideal bariatric surgery , and the efficacy of this surgery is not inferior to that of gastric bypass BACKGROUND Laparoscopic sleeve gastrectomy ( LSG ) is an approved primary procedure for morbid obesity , but it is associated with serious complications , such as staple line leaks and bleeding . The objective of this study was to assess the effectiveness of staple line reinforcement ( SLR ) in reducing leaks and bleeding after LSG . METHODS A total of 1162 patients underwent LSG ( 305 males , 857 females ) . The mean age was 43.7 years and the mean body mass index was 48 kg/m(2 ) . The patients were divided into 6 groups based on the type of SLR , including a no-SLR control group , with evaluation of leaking and bleeding risk and correlation of patients ' characteristics with complications . RESULTS A total of 189 patients underwent LSG without reinforcement . The SLR method was oversewing in 476 patients , bovine pericardium in 312 , synthetic polyester in 76 , glycolide/trimethylene copolymer in 63 , and thrombin matrix in 46 . The overall leak frequency was 2.8 % ; higher with synthetic polyester ( 7.8 % ) , 4.8 % with no reinforcement , and lower with bovine pericardium strips ( .3 % ; P<.01 ) . Postoperative hemorrhage occurred in 35 patients ( 3 % ) , with a higher frequency being observed without SLR ( 13.7 % ; P = .02 ) . Only diabetes was a risk-factor for a leak ( P < .01 ) . CONCLUSION SLR with bovine pericardium strips significantly reduced the leak risk . Postoperative bleeding was significantly lower with all SLR- methods , although there was no significant difference among the various techniques . Patients with type II diabetes had a higher risk of staple line leak after LSG . Further r and omized , controlled studies are needed to improve our underst and ing of the efficacy of SLR during LSG Background Obesity is linked to cardiac disorders with a relative risk of atrial fibrillation of 1.5 ( requiring the use of chronic anticoagulation therapy , CAT ) . However , CAT is a known risk factor for postoperative bleeding after elective surgery . The primary objective of the present study was to evaluate the short- and long-term complications of laparoscopic sleeve gastrectomy ( LSG ) in patients receiving CAT . Methods This is a retrospective analysis of a prospect i ve data base of CAT patients undergoing LSG between March 2004 and December 2012 . This LSG-CAT group was matched 1:2 on preoperative data with patients not receiving CAT ( LSG-control group ) . Primary efficacy criterion was the frequency of CAT-related complications . Secondary efficacy criteria were the major postoperative complications , frequency of revisional surgery , long-term CAT-related complications , and a change in the dose level of oral anticoagulants . Results The LSG-CAT group consisted of 15 patients with a median age of 54 years ( 32–65 ) . The LSG-control group consisted of 30 patients . Median operating time was 75 min in both groups ( p = 0.33 ) . Major complication rates in the LSG-CAT and LSG-control groups were 13.3 and 3.3 % , respectively ( p = 0.20 ) , with one case of postoperative bleeding in each group ( 6.7 and 3.3 % , p = 0.6 ) ; incidence of revisional surgery was 13.3 and 3.3 % ( p = 0.2 ) . There were no postoperative mortalities . After a median follow-up of 14 months ( 9–43 ) , no changes in the dose level of oral anticoagulants were reported . Conclusions LSG in patients receiving CAT is not associated with CAT-specific complications . This surgical procedure enables good weight loss and does not require change in the dose level of oral anticoagulants BACKGROUND Through efficacy and improved safety , multiport laparoscopic sleeve gastrectomy ( LAPS-G ) has emerged as an important and broadly available treatment option for people with severe and complex obesity . Because a single-incision laparoscopic sleeve gastrectomy ( SILS-G ) would be less invasive , we applied this novel surgical technique for a selected number of patients enrolled into our minimally invasive bariatric program . SUBJECTS AND METHODS A retrospective review of prospect ively collected data from 80 morbidly obese patients who qualified for SILS-G or LAPS-G was performed from January 2011 to May 2012 . RESULTS SILS-G and LAPS-G were performed in 40 patients , respectively . All patients were female . Mean age was 41 ( range , 19 - 73 ) years ( SILS-G , 37 [ 19 - 62 ] years ; LAPS-G , 43 [ 24 - 73 ] years ; P = not significant ) . Preoperative body mass index was 40.8 ( 35.1 - 45.0 ) kg/m(2 ) in the SILS-G group and 43.8 ( 35.0 - 47.8 ) kg/m(2 ) in the LAPS-G group ( P = not significant ) . Total operative time was significantly lower in the SILS-G group ( 85±21 minutes ) compared with the LAPS-G group ( 97±26 minutes ) ( P<.05 ) . Median percentage excess weight loss was comparable in both groups ( SILS-G , 57.2 % ; LAPS-G , 53.7 % ) at 6.6 months after surgery . Mean hospital stay was 5 days ( SILS-G , 5 [ 4 - 24 ] days ; LAPS-G , 6 [ 4 - 14 ] days ; P = not significant ) . Complication rates were low in both groups : leakage , 2.5 % in SILS-G and 0 % in LAPS-G ; bleeding , 2.5 % in SILS-G and 2.5 % in LAPS-G ; and trocar-site hernia , 0 % in both groups . Patients operated on with single-incision laparoscopy had a significantly better cosmetic outcome as assessed by a scar satisfaction assessment question naire ( P<.01 ) . CONCLUSIONS SILS-G is a feasible and safe operative procedure that leads to a significant reduction of total operative time compared with a multiport access procedure . Further potential benefits associated with single-incision laparoscopic surgery remain to be investigated objective ly Laparoscopic sleeve gastrectomy has gained popularity and acceptance among bariatric surgeons , mainly as a result of its low morbidity and mortality . Single-incision laparoscopic surgery ( SILS ) , the most recent development in minimally invasive surgery , allows operations to be carried out through only a single incision using special ports . To further minimize the trauma of access incisions , we applied the SIL sleeve gastrectomy on a selected number of patients enrolled into our minimally invasive bariatric program . Between June 2010 and May 2012 , 40 consecutive female patients underwent SIL sleeve gastrectomy . All data ( demographic , morphologic , operative , and follow-up data ) were prospect ively collected in a computerized data bank . All patients were female . Mean age was 37 years ( range , 19 to 62 years ) , preoperative body mass index was 40.8 kg/m(2 ) ( range , 35.1 to 45.0 kg/m(2 ) ) , and excess weight loss was 57.2 per cent at 6.6 months after surgery . Total operative time was 85 ± 21 minutes and mean hospital stay was 5 days ( range , 4 to 24 days ) . Of the patients , two ( 5 % ) sustained postoperative complications such as leakage from the suture line and hemorrhage one in each case . There was no trocar site hernia . SIL sleeve gastrectomy seems to be an effective surgical option for the treatment of morbid obesity . During the first 6 months after the operation , weight loss was excellent . These results are at present comparable to those of multiport sleeve gastrectomy . SIL sleeve gastrectomy is safe and feasible and can be performed without changing the existing principles of this procedure Objective . This prospect i ve study evaluated laparoscopic sleeve gastrectomy for its safety and efficiency in excess weight loss ( % EWL ) in super superobese patients ( BMI > 60 Kg/m2 ) . Results . Thirty patients ( 33 women and 7 men ) were included , with mean age of 35 years ( range 18 to 59 ) . Mean preoperative BMI was 66 Kg/m2 ( range 60 to 85 ) . The study included one patient with complete situs inversus and 4 ( 14 % ) with previous restrictive gastric b and ing . The mean operative time was 120 minutes ( range 80 to 220 min ) and the mean hospital stay was 7.5 days ( 4 to 28 days ) . There was no postoperative mortality or need for a laparotomy conversion . Two subphrenic hematomas , one gastric fistula , and one pulmonary embolism , were the major complications . After 18 months 17 ( 77 % ) had sufficient weight loss and six had insufficient results , leading to either re-sleeve gastrectomy ( 3 ) , or gastric bypass ( 2 ) . Three years after the initial laparoscopic sleeve gastrectomy , the mean EWL was 51 % ( range 21 to 82 ) . Conclusion . The laparoscopic sleeve gastrectomy is a safe and efficient operating procedure for treating super superobesity . In the case of insufficient weight loss , a second-stage operation like resleeve gastrectomy or gastric bypass can be proposed Background In recent years , there has been renewed interest in using robotics in bariatric surgery for the treatment of morbid obesity . However , the high cost of a robotic surgical system has hindered its widespread use in developing countries . This study aims to compare the rate of morbidity , weight loss , and relative costs between laparoscopic ( LSG ) and robotic-assisted sleeve gastrectomy ( RSG ) performed for the treatment of obesity in a single center in Brazil . Methods From January 2011 to March 2013 , 48 severely obese patients underwent either LSG or RSG at our institution and were prospect ively followed up for 12 months . Patients were free to choose either approach and were informed of any extra costs that may be incurred Results Thirty-two patients underwent LSG and 16 patients , RSG . No significant differences were observed between LSG and RSG groups regarding age , sex , BMI , incidence of comorbidities , duration of surgery , and length of hospital stay . Also , there were no significant between-group differences in BMI values evaluated at 6 and 12 months after surgery . Surgical costs were almost twice as high and total hospital costs were approximately 50 % higher in the robotic approach compared to the laparoscopic approach Conclusion Both RSG and LSG had excellent and similar post-operative clinical outcomes . However , the much higher costs of purchasing and maintaining the robotic system are still precluding the use of RSG as a routine approach in the treatment of morbid obesity in Brazil INTRODUCTION Single port instrument delivery extended reach ( SPIDER ( ® ) ) surgical system is a revolutionary surgical platform that allows triangulation of the surgical instruments while eliminating the crossing of instruments , the problematic characteristic of single access laparoscopic surgery . METHODS The purpose of this study was to analyze our initial experience with SPIDER ( ® ) sleeve gastrectomy and to present the technical details of this new minimally invasive approach , performed in ten patients at the La Casamance Private Hospital between November 2012 and April 2013 . All patients were review ed at scheduled post-operative consultations at 1 , 3 and 6 months . In addition to clinical examination , the post-operative consultation at one month also included a satisfaction survey using the Moorehead-Ardelt question naire . RESULTS An initial series of ten sleeve gastrectomies were performed in female patients with a mean age of 41.5 years ( range : 2 - 52 ) . The mean BMI was 40.11 ( range : 37.25 - 44.3 ) . The intervention was performed through a single trocar in all patients with no " conversion " to classic laparoscopy or open surgery . The mean operative time was 61 ± 15.22 minutes ( SD = st and ard deviation ) ( range : 43 - 96 min ) . The mean BMI at one month was 35.5 ( SD:± 3.58 , SEM : ± 1.13 ) ( SEM = st and ard error of mean ) with an average percentage of excess weight loss ( % EWL ) of 32.9 % ( SD:± 8.56 % , SEM:± 2.71 % ) . The mean BMI at three months was 32.4 ( SD : ± 2.78 , SEM : ± 0.88 ) with an average % EWL of 52.7 % ( SD : ± 8.64 % , SEM : ± 2.73 % ) . The mean BMI at six months was 29.9 ( SD:± 2.60 , SEM : ± 0.98 ) with a mean % EWL of 68.8 % ( SD : ± 8.38 % , SEM:± 3.17 % ) . Complete remission of co-morbid conditions was observed in four patients , improvement in three others , and no change in a single patient . The mean duration of hospitalization was 3.1 days . The mean follow-up period was 161 days ( SD:± 57.4 days , range : 90 - 243 days ) . There was no mortality and no intra-operative and post-operative complications were noted . CONCLUSIONS The SPIDER ( ® ) surgical platform seems to be a usable and effective method for performance of minimally invasive single-access sleeve gastrectomy , offering an easy and efficient operative procedure compared to other single-port systems . Prospect i ve long-term studies are recommended before this approach can be vali date d to be of comparable efficiency to conventional multi-port laparoscopic surgery BACKGROUND Venous thromboembolism is the most common postoperative medical complication after bariatric surgery . Mortality associated with thromboembolic processes can reach up to 50%-75 % . The aim of this study was to determine the incidence of deep vein thrombosis ( DVT ) and portal-splenic-mesenteric vein thrombosis ( PSMVT ) in our population undergoing laparoscopic sleeve gastrectomy ( LSG ) as the bariatric technique , with an anti-thromboembolic dosage scheme of 0.5 mg/kg/day 12 hours preoperatively and maintained during 30 days postoperatively . PATIENTS AND METHODS A prospect i ve observational study was performed , including 100 consecutive patients undergoing LSG between October 2007 and September 2013 . To determine the incidence of DVT and PSMVT , all patients undergo contrast-enhanced abdominal computed tomography ( CT ) and Doppler ultrasonography ( US ) of both lower limbs on the third postoperative month , whether they were asymptomatic or symptomatic . RESULTS Contrast-enhanced CT showed 1 case of PSMVT ( 1 % ) . Two patients presented DVT in the right leg ( 2 % ) . All the cases were asymptomatic . CONCLUSIONS The incidence of PSMVT and DVT after LSG with a prophylactic low-molecular-weight heparin dose of 0.5 mg/kg/day and maintained during 30 days postoperatively is 1 % and 2 % , respectively . According to these results , a postoperative screening with Doppler US and /or contrast-enhanced CT seems to be unnecessary Background Bariatric surgery is the most effective treatment for gastro-esophageal reflux disease ( GERD ) in obese patients , with the Roux-en-Y gastric bypass being the technique preferred by many surgeons . Published data reporting the results of laparoscopic sleeve gastrectomy ( LSG ) in patients with GERD are contradictory . In a previous observational study , we found that relative narrowing of the distal sleeve , hiatal hernia ( HH ) , and dilation of the fundus predispose to GERD after LSG . In this study , we evaluated the effects of st and ardization of our LSG technique on the incidence of postoperative symptoms of GERD . Methods This was a concurrent cohort study . Patients who underwent bariatric surgery at our center were followed prospect ively . LSG was performed in all patients in this series . Results A total of 234 patients underwent surgery . There were no cases of death , fistula , or conversion to open surgery . All 134 patients who completed 6–12 months of postoperative follow-up were evaluated . Excess weight loss at 1 year was 73.5 % . In the study group , 66 patients ( 49.2 % ) were diagnosed with GERD preoperatively , and HH was detected in 34 patients ( 25.3 % ) intraoperatively . HH was treated by reduction in three patients , anterior repair in 28 , and posterior repair in three . Only two patients ( 1.5 % ) had symptoms of GERD at 6–12 months postoperatively . Conclusions Our results confirm that careful attention to surgical technique can result in significantly reduced occurrence of symptoms of GERD up to 12 months postoperatively , compared with previous reports of LSG in the literature Background The most frequent and most feared complication after laparoscopic sleeve gastrectomy ( LSG ) is gastric leak ( GL ) . We hypothesize that botulinum neurotoxin ( botulinum type A ( BTX-A ) ) injection into the pyloric sphincter muscle at the time of operation may decrease the risk of postoperative GL . Methods Consecutive patients with morbid obesity ( MO ) treated by LSG were enrolled . Patients were r and omly allocated into two groups : group I ( intrapyloric BTX-A injection was performed ) and group II ( no injection was performed ) . The primary outcome measure was number of patients developing GL . Secondary outcome measures were percent of excess weight loss , postoperative complications , and their management . Results One hundred and fifteen patients ( 86 ( 74.8 % ) females ) were r and omized into two groups of 57 patients ( group I ) and 58 patients ( group II ) . Four patients in group II developed GL versus no patient in group I ( P = 0.04 ) . Ten patients in group I and two in group II developed refractory epigastric pain ( P = 0.01 ) . Other complication rates were comparable for both groups . Mean preoperative BMI of patients in both groups had significantly decreased from 54.64 ± 6.82 to 42.99 ± 5.3 at 6 months and to 39.09 ± 5.14 at 12 months ( P < 0.001 ) . Conclusions LSG is an effective , safe , and minimally invasive procedure for treatment of MO . No patient in whom pyloric BTX-A injection was performed developed postoperative GL versus four patients in whom injection was not performed . The difference in GL rate was statistically significant , thus favoring the use of pyloric BTX-A injection during LSG Abstract Introduction : LigaSure ™ was developed as an alternative to suture ligatures , hemoclips and staplers for ligating vessels and tissue bundles . The aim of the present study was to determine whether LigaSure can be used as a welding instrument in the performance of laparoscopic sleeve gastrectomy . Material and methods : Gastric specimens were assigned into four groups . Group 1 - specimens remained with the staple line intact . Group 2 - the staple line was oversewn . Group 3 - the staple line was resected with LigaSure . Group 4 - staple line was resected with LigaSure and the seal was oversewn . In all specimens the pressure tolerance was assessed using a portable sensor . Results : In group 1 the leak pressure was 34.7 ± 11.7 whereas in group 2 specimens the pressure increased three-fold ( 101.9 ± 21.4 ) . The LigaSure seal alone ( group 3 ) achieved a mean pressure of 13.7 mmHg . However , in group 4 there was an exponential increase on their burst strength up to 142 mmHg ( p = 0.0005 ) . Conclusion : According to our results , LigaSure could be used to perform laparoscopic sleeve gastrectomy with reduction of staple-line bleeding and , when reinforced with a running suture , it achieves a strength that approaches that of staples plus oversewing OBJECTIVE An experience with laparoscopic sleeve gastrectomy using the natural orifice specimen extraction ( NOSE ) technique . BACKGROUND Bariatric surgery is nowadays the only long term effective obesity treatment method . METHODS Twenty one consecutive patients underwent laparoscopic sleeve gastrectomy with the use of natural orifice specimen extraction ( NOSE ) in the Surgical Clinic of Faculty Hospital Ostrava between May 2012 and August 2012 . Inclusion criteria were the body mass index ( BMI ) higher than 35 kg/m2 or higher than 32 kg/m2 accompanied with relevant comorbidities . RESULTS Among 21 patients in this series , there were three men ( 14.3 % ) and 18 women ( 85.7 % ) . Their mean age was 40.9±10.2 years . Their mean preoperative BMI was 40.4±4.6 kg/m2 . No patient had previous bariatric surgery , one patient had laparoscopic fundoplication . All operations were completed laparoscopically with no conversions to an open procedure . In two cases , laparoscopic cholecystectomy was performed and the gallbladder was extracted along with the gastric specimen by transgastric approach . CONCLUSION Laparoscopic sleeve gastrectomy is a safe and effective bariatric procedure with low morbidity and mortality . Based on our initial experiences it could be an indication for NOSE with transgastric approach . Obese patients would benefit from this approach due to the elimination of wound complications ( Tab . 2 , Fig. 3 , Ref . 22 ) Background : Laparoscopic sleeve gastrectomy ( SG ) is an upcoming procedure in bariatric surgery and is currently performed worldwide . Staple line leakage , as the most frequent and most feared complication , is still a major concern . Methods : Since 2005 data from patients undergoing bariatric procedures in Germany have been prospect ively registered in an online data base and analyzed . All patients who had undergone primary SG within a 7-year period were considered for analysis . Results : Using the German Bariatric Surgery Registry , data from more than 11,800 SGs were collected between January 1 , 2005 , and December 31 , 2013 . Staple line leak rate decreased from 6.5 % to 1.4 % . Male sex , higher body mass index , concomitant sleep apnea , conversion to laparotomy , longer operation time , a combination of buttresses and oversewing , and the occurrence of intraoperative complications were associated with a significantly higher leakage rate compared with when using either buttresses or oversewing alone . On multivariable analysis , operation time and year of procedure only had a significant impact on staple line leakage rate . Conclusions : Owing to the growing experience a constant decrease in the leakage rate after SG has been observed . Staple line disruption may still lead to sepsis , multiorgan dysfunction , and increased mortality . The results of the current study demonstrated that there are factors that increase the risk of leakage and which would enable surgeons to define risk groups , select patients more carefully , and offer closer follow-up during the postoperative course with early recognition and adequate treatment BACKGROUND Clinical outcomes after many complex surgical procedures vary widely across hospitals and surgeons . Although it has been assumed that the proficiency of the operating surgeon is an important factor underlying such variation , empirical data are lacking on the relationships between technical skill and postoperative outcomes . METHODS We conducted a study involving 20 bariatric surgeons in Michigan who participated in a statewide collaborative improvement program . Each surgeon su bmi tted a single representative videotape of himself or herself performing a laparoscopic gastric bypass . Each videotape was rated in various domains of technical skill on a scale of 1 to 5 ( with higher scores indicating more advanced skill ) by at least 10 peer surgeons who were unaware of the identity of the operating surgeon . We then assessed relationships between these skill ratings and risk-adjusted complication rates , using data from a prospect i ve , externally audited , clinical - outcomes registry involving 10,343 patients . RESULTS Mean summary ratings of technical skill ranged from 2.6 to 4.8 across the 20 surgeons . The bottom quartile of surgical skill , as compared with the top quartile , was associated with higher complication rates ( 14.5 % vs. 5.2 % , P<0.001 ) and higher mortality ( 0.26 % vs. 0.05 % , P=0.01 ) . The lowest quartile of skill was also associated with longer operations ( 137 minutes vs. 98 minutes , P<0.001 ) and higher rates of reoperation ( 3.4 % vs. 1.6 % , P=0.01 ) and readmission ( 6.3 % vs. 2.7 % ) ( P<0.001 ) . CONCLUSIONS The technical skill of practicing bariatric surgeons varied widely , and greater skill was associated with fewer postoperative complications and lower rates of reoperation , readmission , and visits to the emergency department . Although these findings are preliminary , they suggest that peer rating of operative skill may be an effective strategy for assessing a surgeon 's proficiency Background Laparoscopic sleeve gastrectomy ( LSG ) is a surgical technique that treats morbid obesity . Methods Consecutive patients with morbid obesity treated by LSG at our department were evaluated . Patients enrolled in the study were r and omized into group I ( LSG begins the division 2 cm from the pylorus ) and group II ( LSG begins the division 6 cm from the pylorus ) . The primary outcome measure was the percent of excess weight loss ( % EWL ) ; secondary outcomes included postoperative morbidity and mortality and improvement of comorbidity . Results One hundred five patients ( 79 ( 75.2 % ) were females ) were r and omized into two groups of ( GI ) 52 patients and ( GII ) 53 patients . In group I , the mean % EWL was 51.8 ± 13.9 , 63.8 ± 16.1 and 71.8 ± 12 ; however , in group II , the mean % EWL was 38.3 ± 10.9 , 51.9 ± 13.6 and 61 ± 11.1 at 6 , 12 , and 24 months , respectively ( P = 0.0001 , 0.0001 , 0.003 ) . There was weight regain after 2 years in five patients in group II and only one patient in group I ( P = 0.09 ) . There was no significant difference between both group as regards gastric leakage , vomiting or GER . There was significant improvement in comorbidity after LSG in both groups , but no significant difference between them . Hospital mortality occurred in group II in one case as a result of gastric leakage . Conclusions LSG is a safe and effective procedure with good short-term outcome . Increasing the size of the resected antrum is associated with better weight loss without increasing the rate of complications significantly BACKGROUND Data regarding the management of bariatric patients with cirrhosis are scarce , and there is no strong evidence that supports a specific approach for this group of patients . The aim of this study was to review our experience with cirrhotic patients undergoing bariatric surgery . METHODS A prospect ively maintained data base was review ed to assess the outcomes of bariatric surgery for patients with known cirrhosis and for patients with cirrhosis discovered at surgery ( unknown cirrhosis ) . RESULTS From April 2004 to September 2011 , 23 patients ( 12 with known cirrhosis and 11 with unknown cirrhosis ) met inclusion criteria . There were 14 females and 9 males with a mean age of 51.5 ± 8.3 and a mean body mass index of 48.2 ± 8.6 kg/m2 . Child-Pugh classes were A ( n = 22 ) and B ( n = 1 ) . Patients had a high frequency of diabetes ( 83 % ) , dyslipidemia ( 61 % ) , and hypertension ( 83 % ) . Procedures performed were laparoscopic Roux-en-Y gastric bypass ( LRYGB ) ( n = 14 ) , laparoscopic sleeve gastrectomy ( LSG ) ( n = 8) , and laparoscopic adjustable gastric b and ing ( n = 1 ) . Two patients underwent LSG successfully after transjugular intrahepatic portosystemic shunt . Mean length of hospital stay was 4.3 ± 2.7 days . Complications developed in 8 patients . One patient died of unknown cause 9 months after surgery . No patients had liver decompensation after surgery . The patients lost 67.4 % ± 30.9 % of their excess weight at 12 months follow-up and 67.7 % ± 24.8 % at 37 months follow-up . CONCLUSION LRYGB and LSG can be performed without prohibitive complication rates in carefully selected patients with cirrhosis . In our experience , bariatric patients with cirrhosis achieved excellent weight loss and improvement in obesity-related co-morbidities Introduction Roux-en-Y gastric bypass ( RYGB ) is considered the gold st and ard bariatric procedure with documented safety and effectiveness . Laparoscopic sleeve gastrectomy ( LSG ) is a newer procedure being done with increasing frequency . R and omized comparisons of LSG and other bariatric procedures are limited . We present the results of the first prospect i ve r and omized trial comparing LSG and RYGB in the Polish population . Aim To assess the efficacy and safety of LSG versus RYGB in the treatment of morbid obesity and obesity-related comorbidities . Material and methods Seventy-two morbidly obese patients were r and omized to RYGB ( 36 patients ) or LSG ( 36 patients ) . Both groups were comparable regarding age , gender , body mass index ( BMI ) and comorbidities . The follow-up period was at least 12 months . Baseline and 6 and 12 month outcomes were analyzed including assessment of percent excess weight lost ( % EWL ) , reduction in BMI , morbidity ( minor , major , early and late complications ) , mortality , reoperations , comorbidities and nutritional deficiencies . Results There was no 30-day mortality and no significant difference in major complication rate ( 0 % after RYGB and 8.3 % after LSG , p > 0.05 ) or minor complication rate ( 16.6 % after RYGB and 10.1 % after LSG , p > 0.05 ) . There were no early reoperations after RYGB and 2 after LSG ( 5.5 % ) ( p > 0.05 ) . Weight loss was significant after RYGB and LSG but there was no difference between both groups at 6 and 12 months of follow-up . At 12 months % EWL in RYGB and LSG groups reached 64.2 % and 67.6 % respectively ( p > 0.05 ) . There was no significant difference in the overall prevalence of comorbidities and nutritional deficiencies . Conclusions Both LSG and RYGB produce significant weight loss at 6 and 12 months after surgery . The procedures are equally effective with regard to % EWL , reduction in BMI and amelioration of comorbidities at 6 and 12 months of follow-up . Laparoscopic sleeve gastrectomy and RYGB are comparably safe techniques with no significant differences in minor and major complication rates at 6 and 12 months Summary Background The transumbilical route began being clinical ly feasible with or without unique access devices . Setting The setting for this study was a private practice at Clínica Las Condes , Santiago , Chile . Objective The objective was to describe our experience performing a laparoscopic sleeve gastrectomy ( LSG ) via transumbilical route using a single-port access device in addition to st and ard laparoscopic instruments . Method A prospect i ve nonr and omized protocol was applied to patients fulfilling the following inclusion criteria : to have been medically indicated for an LSG , to have a body mass index ( BMI ) of less than or equal to 40 kg/m2 , and the distance between the xiphoid appendix and umbilicus should be less than 22 cm . All patients were female with a median ( p50 ) age of 34.5 ( ranging from 21 to 57 ) years , a median weight of 92 ( ranging from 82.5 to 113 ) kg , and a median BMI of 35.1 ( ranging from 30.5 to 40 ) kg/m2 . The device insertion technique , the gastrectomy , and postoperative management are described . Results LSG via transumbilical route was successfully carried out in 19 of the 20 patients in whom the procedure was performed ; one patient had to be converted to a conventional laparoscopic procedure . Mean operating time was 127 ( ranging from 90 to 170 ) min . On the second postoperative day , all patients were assessed through an upper gastrointestinal barium-contrasted radiological series . There was neither morbidity nor mortality in this group . Excess weight loss at 25 months after surgery was 114 % . Conclusions Single-port LSG can be successfully performed in selected obese patients with a BMI of less than 40 kg/m2 using traditional laparoscopic instruments . The technique allows performing a safe and effective vertical gastrectomy Objective : Laparoscopic sleeve gastrectomy ( LSG ) has been proposed as an effective alternative to the current st and ard procedure , laparoscopic Roux-en-Y gastric bypass ( LRYGB ) . Prospect i ve data comparing both procedures are rare . Therefore , we performed a r and omized clinical trial assessing the effectiveness and safety of these 2 operative techniques . Methods : Two hundred seventeen patients were r and omized at 4 bariatric centers in Switzerl and . One hundred seven patients underwent LSG using a 35-F bougie with suturing of the stapler line , and 110 patients underwent LRYGB with a 150-cm antecolic alimentary and a 50-cm biliopancreatic limb . The mean body mass index of all patients was 44 ± 11.1 kg/m2 , the mean age was 43 ± 5.3 years , and 72 % were female . Results : The 2 groups were similar in terms of body mass index , age , sex , comorbidities , and eating behavior . The mean operative time was less for LSG than for LRYGB ( 87 ± 52.3 minutes vs 108 ± 42.3 minutes ; P = 0.003 ) . The conversion rate was 0.9 % in both groups . Complications ( < 30 days ) occurred more often in LRYGB than in LSG ( 17.2 % vs 8.4 % ; P = 0.067 ) . However , the difference in severe complications did not reach statistical significance ( 4.5 % for LRYGB vs 1 % for LSG ; P = 0.21 ) . Excessive body mass index loss 1 year after the operation was similar between the 2 groups ( 72.3 % ± 22 % for LSG and 76.6 % ± 21 % for LRYGB ; P = 0.2 ) . Except for gastroesophageal reflux disease , which showed a higher resolution rate after LRYGB , the comorbidities and quality of life were significantly improved after both procedures . Conclusions : LSG was associated with shorter operation time and a trend toward fewer complications than with LRYGB . Both procedures were almost equally efficient regarding weight loss , improvement of comorbidities , and quality of life 1 year after surgery . Long-term follow-up data are needed to confirm these facts Background Staple line bleeding ( SLB ) is a common intraoperative complication following resection in laparoscopic sleeve gastrectomy ( SG ) . Opinion is divided on the best measure to deal with SLB which includes expensive reinforcement strategies , suturing the staple line or diathermy . Tranexemic acid is a relatively inexpensive drug known to reduce bleeding in trauma and surgery . The aim of this study was to evaluate whether intraoperative tranexemic acid reduces staple line bleeding . Methods In this prospect i ve matched comparative study of SG , one cohort of patients was administered tranexemic acid ( 1 g ) after induction and compared to a control group . The primary outcome compared the number of staple line bleeding points requiring intervention intra-operatively . Secondary outcomes included estimated blood loss and operating time . The anaesthetic and thromboprophylaxis protocol s were uniform . Operative technique and stapling equipment were identical in all patients . Results Twenty-five patients were allocated to both the control and treatment arms . Patient characteristics in both groups were similar in age ( median 34 vs 43 years ) , body mass index ( median 54.7 vs 52 kg/m2 ) , gender distribution ( female : male = 20:5 ) and co-morbidities . The treatment group receiving tranexemic acid , required significantly less number of haemostatic stitches for staple line bleeding ( 19 vs 46 , p < 0.05 ) , incurred less intraoperative blood loss ( p < 0.01 ) and had quicker operating times ( median 66 vs 80 min , p < 0.05 ) . There was no difference in morbidity or mortality in both groups . Conclusion Intraoperative prophylactic tranexemic acid use is a simple and economical option for effectively reducing staple line bleeds leading to significant decrease in operating times Abstract Background Crural closure in addition to laparoscopic sleeve gastrectomy ( LSG ) represents a valuable option for the synchronous management of morbid obesity and hiatal defects , providing good outcomes in terms of weight loss and gastroesophageal reflux disease ( GERD ) symptoms control . The aim of this prospect i ve study was to evaluate the safety and effectiveness of the reinforced cruroplasty during LSG compared with a concurrent group of simple cruroplasty . Methods The study groups included 96 morbidly obese patients who underwent simultaneous LSG and cruroplasty . Group A : 48 patients with hiatal areal defect < 4 cm2 and normal pillars ( simple posterior cruroplasty ) ; group B : 48 patients with hiatal areal defect > 4 and < 8 cm2 with weakness of the right pillar ( on-lay synthetic absorbable mesh-reinforced cruroplasty ) . Upper GI symptoms were assessed by Roma III st and ard question naire . Endoscopy , imaging , esophageal 24-h pH monitoring and HR manometry were performed in cases of persistent or recurrent symptoms after surgery . Results Mortality rate was nil . The conversion rate to open was 1 % . Intra-operative diagnosis of hiatal hernia occured in 41 patients ( 42.7 % ) . Mesh-related complications were none . Perioperative complications occurred in four patients ( 4.1 % ) . After 19- to 21-month follow-up , GERD symptom remission occurred in 89 % of patients . GERD symptoms were detected postoperatively in eight patients : six in group A ( five symptomatic and radiological recurrences and one persistent ) and two in group B ( one persistent and one de novo GERD ) ( P < 0.05 ) . Conclusions The synthetic absorbable mesh offers an effective option for crural repair during LSG with no clinical recurrences at 19 months . The midterm results of this prospect i ve comparative study evaluating two different technical options for cruroplasty confirm that the simultaneous procedures are safe and cruroplasty is effective in mild-to-moderate GERD control Background Leaks after laparoscopic sleeve gastrectomy ( LSG ) are serious complications of this procedure . The objective of the present study was to evaluate the costs of leaks after LSG . Setting Private hospital , France . Methods A retrospective analysis was conducted on a prospect i ve cohort of 2012 cases of LSG between September 2005 and December 2014 . Data were collected on all diagnostic and therapeutic measures necessary to manage leaks , ward , and intensive care unit ( ICU ) length of stay . Additional outpatient care was also analyzed . Results Twenty cases ( 0.99 % ) of gastric leak were recorded . Fifteen patients had available data for cost analysis . Of these , 13 patients were women ( 86.7 % ) with a mean age of 41.4 years ( range 22–61 ) and mean BMI of 43.2 kg/m2 ( range 34.8–57.1 ) . The leaks occurred after 7.4 days ( ±2.3 ) postoperatively . Only one gastric leak was recorded for the last 800 cases in which absorbable staple line reinforcement was used . Mean intra-hospital cost was 34398 € ( range 7543–91,632 € ) . Prolonged hospitalization in ICU accounted for the majority of hospital costs ( 58.9 % ) . Mean additional outpatient costs for leaks were 41,284 € ( range 14,148–75,684 € ) . Conclusions Leaks after LSG are an expensive complication . It is therefore important to take all necessary measures to reduce their incidence . Our data should be considered when analyzing the cost effectiveness of staple line reinforcement usage Background The aim of this study was to evaluate the effectiveness and safety of laparoscopic sleeve gastrectomy ( LSG ) for the treatment of obesity in ethnic Chinese in Hong Kong . Methods Seventy consecutive Chinese patients ( 49 females ; mean age 34.7 ± 8.8 [ range 18–56 ] years ) received LSG for the treatment of obesity from May 2006 to Nov 2007 as a st and -alone procedure for weight reduction . Mean baseline body weight ( BW ) and body mass index ( BMI ) were 108.9 ± 22.1 kg ( range 71.0–164.9 kg ) and 40.7 ± 7.8 kg/m2 ( range 27.4–68.4 kg/m2 ) , respectively . Outcome measures were collected and assessed in a prospect i ve manner . Results All procedures were performed laparoscopically with no conversion . There was neither mortality nor any postoperative complications that required reoperation . Major complication occurred in two patients ( 2.9 % ; esophagogastric junction [ EGJ ] leak and stomach tube stricture ) . Mean follow-up was 7.1 ± 5.0 months . Mean procedure time was 90.6 ± 39.4 min , and mean hospital stay was 3.8 ± 2.3 days . Mean BMI loss was 6.3 ± 2.5 , 9.0 ± 3.4 and 12.3 ± 4.5 kg/m2 at 3 , 6 , and 12 months . Mean percent of excess BW loss was 48.5 ± 28.4 , 69.7 ± 31.7 , and 63.5 ± 29.4 at 3 , 6 , and 12 months . Conclusion LSG is safe and effective in achieving significant weight loss in obese ethnic Chinese patients Background and AimS taple line complications and axial rotation of the gastric tube after sleeve gastrectomy are well-recognized complications of the procedure . The present study aims to investigate the role of staple line inversion and distal fixation to the transverse mesocolon in reducing these complications . Patients and Methods This is a retrospective analysis of prospect ively collected data of 252 patients with morbid obesity who underwent laparoscopic sleeve gastrectomy ( LSG ) . Patients were subdivided into two groups : group I comprising 124 patients did not have distal sleeve fixation and group II comprising 128 patients underwent staple line inversion and distal fixation . Results Patients were 171 females and 81 males with a mean age of 33.2 ± 8.7 years and a mean preoperative body mass index ( BMI ) of 50.9 ± 8.6 Kg/m2 . The mean operating time was 103.9 ± 26.9 min and the median hospital stay was 1 day . Major complications were detected in 15 ( 5.9 % ) patients , who were all in group I. Group I had significantly shorter operative time and significantly higher rates of staple line bleeding ( 4 % in group I versus 0 in group II ) and gastric axial rotation ( 5.6 % in group I versus 0 in group II ) . There were no significant differences between the two groups regarding early postoperative vomiting ( 21.7 % versus 26.5 % ) and staple line leak ( 2.4 % versus 0 ) . ConclusionS taple line inversion and distal fixation to the transverse mesocolon can be a simple , effective strategy to prevent staple line bleeding , and gastric axial rotation , though it prolonged the operative time of LSG Background The purpose of this paper was to search for predictive factors for proximal leakage after laparoscopic sleeve gastrectomy ( LSG ) in a large cohort from a single referral center . Material s and Methods One thous and seven hundred and thirty-eight patients , collected in a prospect ively held data base from 2008 to 2016 , were retrospectively analyzed . The correlation between postoperative leakage and both preoperative ( age , gender , height , weight , BMI , and obesity-related morbidities ) and operative variables ( the distance from pylorus at which the gastric section was started , operative time , experience of surgeons who performed the LSG , and the surgical material s used ) was analyzed . The experience of the surgeons was calculated in the number of LSGs performed . The surgical material s considered were stapler , cartridges , and reinforcement of the suture . Results Proximal leakage was observed in 45 patients out of 1738 ( 2.6 % ) . No correlation was found between leakage and the preoperative variables analyzed . The operative variables that were found to be associated with lower incidence of leakage at the multivariate analysis ( p < 0.05 ) were the reinforcement of the staple line ( or overriding suture or buttressing material s ) and the experience of the surgeons . A distance of less than 2 cm from the pylorus result ed to be significantly related to a higher incidence of fistula at the univariate analysis . Conclusions In this large consecutive cohort study of LSG , proximal staple line reinforcement ( buttress material or suture ) reduced the risk of a leak . The risk of a proximal leak was much higher in the surgeons first 100 cases , which has implication s for training and supervision during this “ learning curve ” period Background Laparoscopic greater curvature plication ( LGCP ) is an emerging restrictive bariatric procedure that successfully reduces the gastric volume by plication of the gastric greater curvature . The aim of this prospect i ve nonr and omized study was to compare short-term outcomes and associated complications between LGCP and laparoscopic sleeve gastrectomy ( LSG ) . Methods From January 2011 to November 2011 , a total of 39 patients were allocated to undergo either LGCP ( n = 19 ) or LSG ( n = 20 ) . Data on the operative time , complications , hospital stay , overall cost of LSG and LGCP , body mass index loss ( BMI L ) , percentage of excess weight loss ( % EWL ) , loss of appetite and improvement of comorbidities were collected during the follow-up examinations . Results All procedures were completed laparoscopically . The mean operative time was 95.0 ± 17.4 minutes for the LGCP group and 85.5 ± 18.4 minutes for the LSG group ( P = 0.107 ) . No patient required reoperation due to an early complication . One patient in the LSG group was readmitted because of gastric stenosis . The mean hospital stay was 4.2 ± 1.9 days in the LGCP group and 3.9 ± 1.7 days in the LSG group ( P = 0.595 ) . The total cost of LSG was $ 7,826 ± 537 compared to LGCP ( $ 3,358 ± 264 ) ( P < 0.001 ) . One year after surgery , the mean % EWL was 58.8 ± 16.7 % ( n = 11 ) in the LGCP group and 80.0 ± 26.8 % ( n = 11 ) in the LSG group ( P = 0.038 ) . Loss of feeling of hunger was reported in 27.3 % LGCP patients and 72.7 % LSG patients ( P = 0.033 ) at 1 year after surgery . The comorbidities , including diabetes , sleep apnea and hypertension , were markedly improved in both groups 6 months after surgery . Conclusions The short-term outcomes of our study demonstrate that compared with LSG , LGCP is inferior as a restrictive procedure for weight loss , despite its significantly smaller cost . Longer follow-up and prospect i ve comparative trials are needed to confirm the long-term outcomes of this novel procedure and make definitive conclusions Introduction Sleeve gastrectomy has gained popularity over the past decade due to its safety , feasibility , and good results . The purpose of this study is to describe our results , both short and long term , with this procedure . Material and Methods This study is a nonr and omized , controlled , retrospective review of 409 patients who underwent a minimally invasive sleeve gastrectomy at the University of Illinois Hospital and Health System from January 2008 to December 2013 . A total of 304 patients underwent a laparoscopic sleeve gastrectomy , and another 105 patients underwent a robotic procedure using the da Vinci Surgical System ® . Patient demographics , comorbidities , date of surgery , postoperative morbidity and mortality , operating time , length of stay , and excess weight loss were review ed . Results The mean age was 41 years ( 18–70 ) with no statistical difference between the two groups . Patient ’s demographics were similar ( p = 0.395 ) in both groups . The mean operative time for the robotic group was 110.6 versus 84.18 min in the laparoscopic group , which was statistically significant ( p < 0.05 ) . There were no significant differences between the two groups with regard to the perioperative complications , length of stay , or % excess weight loss . Conclusion There is no significant difference between the robotic and laparoscopic group in terms of complications , length of stay , and estimated blood loss . Robot-assisted sleeve gastrectomy is associated with longer operative time and increased cost The main early complications of Laparascopic Sleeve Gastrectomy are bleeding and gastric leakage . Many reinforcement methods are performed in order to reduce these complications . In this prospect i ve , r and omized study , we compared four different techniques to evaluate staple line reinforcement in Laparascopic Sleeve Gastrectomy . Between January 2012 and May 2013 , 65 patients were prospect ively r and omized into four groups in which different techniques were used in h and ling the staple line during Laparascopic Sleeve Gastrectomy . Of the four groups , there was n't any reinforcement used on 15 patients during LSG ( group 1 ) , continuous serosal 3 - 0 prolene sutures were used on 16 patients for staple line reinforcement ( group 2 ) , staple line was supported with v-loc suture in 16 patients ( group 3 ) , and 18 patients had Tisseel fibrin sealant applied throughout the staple line ( group 4 ) . 40 of 65 patients were females , the mean age was 36.8 years ( 20 - 58 years ) , and the mean BMI was 49.2 ( 41 - 60 kg/m² ) . Characteristics of patients among groups were similar . There was n't any significant difference found between groups for BMI . Gastric leakage was detected from the staple line in 2 patients of the v-loc group . According to our results , we demonstrated that good results can be obtained without any reinforcement . Reinforcement with propylene suture only prolongs the operation time , and tissue fibrin sealent increases the cost . In conclusion , we should be more careful using v-loc sutures , and further series with larger numbers are needed to test v-loc BACKGROUND Advanced age has traditionally been considered a relative contraindication to bariatric surgery due to increased perioperative risk and less weight loss . However , it is now being reconsidered in older patients after encouraging results in recent series and the increasing life expectancy . We compared operative and postoperative outcomes of laparoscopic sleeve gastrectomy in patients over 60 years with outcomes in younger patients . We also , analyzed the effect of bariatric surgery on improvement and resolution of co-morbidities in the older group . METHODS From November 2008 to November 2013 , 130 patients underwent laparoscopic sleeve gastrectomy . Of these , 28 patients ( 21.5 % ) were 60 years or older . Outcomes in terms of perioperative complications , short-term and medium-term weight loss , remission or improvement of co-morbidities and medication requirements were extracted from our prospect i ve data base . RESULTS Short-term mortality was 0 % and 30-day complication rate was similar in both groups ( 17.9 % versus 17.6 % according to Clavien-Dindo classification ) . At 12 months postsurgery , older patients had lost 49 % percent of excess weight compared to 60 % in the younger group ( P = 0.012 ) . At 2 years , the results were 45 % versus 60 % , respectively , with P = 0.015 . At least 1 major co-morbidity improved in 65.2 % of older patients . Before surgery , the older group took an average of 4.3 medications compared to 2.7 at 1 year after surgery ( P<0.001 ) . CONCLUSION Laparoscopic sleeve gastrectomy is a safe and effective treatment for morbid obesity in people over 60 years , although younger patients show greater weight loss . Daily medication requirements and co-morbidities decrease significantly in older patients after this procedure Different hormones and peptides involved in inflammation have been studied in and related to obesity . The aim of our work is to assess the variations of different molecules related to inflammation in obese patients during the first year following sleeve gastrectomy . This was a prospect i ve study on patients who underwent sleeve gastrectomy . The variations in different clinical , anthropometric , and analytical parameters related to inflammation were determined and analysed in all patients at the preoperative visit and at the first and fifth days , first and sixth months , and 1 year following surgery . We enrolled 20 patients to the study . The median body mass index ( BMI ) before intervention was 48.5 kg/m2 . With respect to comorbidities , 70 % of the patients had obstructive sleep apnoea syndrome ( OSA ) , 65 % high blood pressure , 45 % dyslipidaemia , and 40 % diabetes mellitus ( DM ) . The median percentage of BMI lost ( % BMI L ) 1 year after the intervention was 71 % . The dyslipidaemia healing or improvement rate was 100 % , whereas it was 87.5 % for diabetes , 84.6 % for hypertension , and 57.1 % for OSA . During the 1-year postintervention period , the average levels of adiponectin increased , although not significantly , whereas those of leptin significantly decreased . In addition , the blood levels of MCP-1 , IL-6 , CRP , ferritin , and PAI-1 significantly decreased in that period . Sleeve gastrectomy is a surgical technique that is associated with improvements in body weight and comorbid conditions from the first postoperative months , which lead to significant variations in the levels of different inflammation-related parameters and a decrease in the levels of leptin , IL-6 , CRP , MCP-1 , ferritin , and serpin ( PAI-1 ) INTRODUCTION The use of the endoscope for the calibration of the gastric sleeve , instead of the st and ard use of the bougie , is a safe procedure and gives the surgeon a higher sense of security . The aim of this study was to evaluate the effect of the use of endoscopic guidance on postoperative complications and mid-term results of the bariatric procedure . PATIENTS AND METHODS A prospect i ve , nonr and omized study was performed at the General University Hospital of Elche ( Alicante , Spain ) between 2010 and 2013 . The patients were divided into the bougie calibration group and the endoscopic calibration group . The decision of which method to use depended on the availability of an endoscopist at the time of the surgery . RESULTS Fifty patients were included in the study , 44 females ( 88 % ) and 6 males ( 12 % ) , with a mean age of 43.3 years and a preoperative mean body mass index of 50.6 kg/m(2 ) . In the endoscopic calibration group , a bleeding point in the staple line was detected and sclerosed with adrenaline in 1 patient . In the bougie calibration group there were no cases of postoperative digestive bleeding . The intraoperative tightness check with blue dye and air insufflation through an orogastric tube in the bougie calibration group was negative in all the patients . In the endoscopic calibration group the check with blue dye was also negative in all cases , but the second test with air detected the exit of air bubbles in 1 case . There were no significant differences in the operation time between groups . A significant reduction in the major complications rate was observed in the endoscopic calibration group ( odds ratio=0.9 ; P=.034 ) . CONCLUSIONS Endoscopic calibration is associated with lower postoperative complications after laparoscopic sleeve gastrectomy Background Gastroesophageal reflux disease ( GERD ) is present in half of morbidly obese patients . Published data reporting the results of laparoscopic sleeve gastrectomy ( LSG ) in patients with GERD are contradictory . We have shown in a previous study that symptoms of GERD can be reduced for up to 12 months after LSG with careful attention to surgical technique . The present study prospect ively evaluated the effect of a st and ardized LSG technique on the incidence of postoperative GERD symptoms in a larger sample , and followed patients for up to 22 months . Methods This was a concurrent cohort study . All patients who underwent LSG at our center completed a st and ard multidisciplinary preoperative evaluation and were followed prospect ively . Results A total of 382 patients underwent surgery . There were no cases of death or fistula . GERD was diagnosed in 170 patients ( 44.5 % ) preoperatively , and hiatal hernia ( HH ) was detected in 142 patients ( 37.2 % ) intraoperatively . Between 6 and 22 months postoperatively , 373 patients were completely evaluated . Ten ( 2.6 % ) had GERD symptoms 6–22 months postoperatively , and 94 % of patients with preoperative GERD symptoms were asymptomatic at follow-up 6–22 months after LSG . Only 1 patient ( 0.5 % ) of a subgroup of 174 without HH or esophagitis at preoperative evaluation had GERD at follow-up . Conclusions Our results confirm that , contrary to previous reports of LSG in the literature , careful attention to surgical technique can result in significantly reduced GERD symptoms up to 22 months postoperatively suggesting that LSG does not predispose patients to GERD during that period Background Little basic science data exists regarding the thickness of transected stomach as the limits of smaller gastric sleeves are created closer to the lesser curvature in laparoscopic sleeve gastrectomy ( SG ) . We sought to determine the tissue thickness trends along the staple line and examine what factors might predispose to thicker tissue . Methods This was a single-center , single-surgeon nonr and omized prospect i ve study of patients undergoing SG . Excised SG specimens , with patient consent , underwent tissue measurement at multiple predetermined locations and at the midpoint of each fired staple cartridge . Results After 9 months , ending in July 2012 , we met our goal enrollment of 50 gastric sleeve specimens . Most of the patients were female ( 80 % ) and white ( 92.5 % ) . Average age was 42 years ( range , 19–60 years ) , and average body mass index ( BMI ) was 49 kg/m2 ( range , 34–82 kg/m2 ) . Tissue thickness was significantly different ( p < 0.01 ) at each location , with the antrum being the thickest at 2.70 mm , followed by the midbody at 2.33 mm , and the fundus at 1.97 mm . Both male gender ( + 0.32 mm , p = 0.04 ) and BMI over 50 kg/m2 ( + 0.33 mm , p < 0.01 ) were associated with thicker tissue , but only in the antrum . The most significant transitions in thickness occurred on the fourth and fifth staple fires , dropping 0.24 mm ( p = 0.02 ) and 0.35 mm ( p < 0.01 ) , respectively . Conclusions Tissue thickness of excised SG specimens varies on the basis of location with the antrum being the thickest . Both BMI ( > 50 kg/m2 ) and gender ( male ) are associated with increased tissue thickness , but only in the antrum . Surgeons should consider using a thicker staple load , such as black , when these factors are present . Also , significant changes in tissue thickness at the fourth and fifth staple fires suggest stepwise alteration in staple cartridge color selection Background Increased visceral adipose tissue is a risk factor for the metabolic complications associated with obesity and promotes a low- grade chronic inflammatory process . Resection of the great omentum in patients su bmi tted to a bariatric procedure has been proposed for the amelioration of metabolic alterations and the maximization of weight loss . The aim of the present study was to investigate the impact of omentectomy performed in patients with morbid obesity undergoing sleeve gastrectomy ( SG ) on metabolic profile , adipokine secretion , inflammatory status , and weight loss . Methods Thirty-one obese patients were r and omized into two groups : SG alone or with omentectomy . Adiponectin , omentin , interleukin-6 ( IL-6 ) , tumor necrosis factor-α ( TNF-α ) , high-sensitivity C-reactive protein ( hs-CRP ) , blood lipids , fasting glucose , insulin , and insulin resistance were measured before surgery and at 7 days , and 1 , 3 and 12 months after surgery . Results During the 1-year follow-up , body mass index ( BMI ) decreased markedly and comparably in both groups ( p < 0.001 ) . Insulin , IL-6 , and hs-CRP levels decreased significantly compared to baseline ( p < 0.05 ) in both groups with no significant difference between groups . Adiponectin and high-density lipoprotein cholesterol levels were significantly and similarly increased compared to baseline ( p < 0.001 ) in both groups . Omentin levels increased significantly ( p < 0.05 ) in the control group and decreased in the omentectomy group 1 year postoperatively . There was no significant change in TNF-α levels in either group . Conclusions The theoretical advantages of omentectomy in regard to weight loss and obesity-related abnormalities are not confirmed in this prospect i ve study . Furthermore , omentectomy does not induce important changes in the inflammatory status in patients undergoing SG Background The surgical technique of laparoscopic sleeve gastrectomy ( LSG ) has not been fully st and ardized yet and there is the unresolved question of what is the optimum size of retained pyloric antrum . The aim of our research was to prove that even after a radical resection of the pyloric antrum the physiological stomach evacuation function can still be preserved . Methods Our study was based on 12 patients , who were r and omly divided into two groups . Patients undergoing radical antrum resection ( RA group ) underwent gastric emptying scintigraphy to determine the evacuation half-time ( T1/2 ) and food retention in the 90th minute of the test ( % GE ) both before the operation and 3 months afterward . Patients in whom the antrum was preserved ( PA group ) served as a control group for comparison of postoperative weight loss ( in kilogram ) , decrease in body mass index ( BMI ) , and decline in excess weight ( % EWL ) . The result ing changes were statistically processed . Results In the RA group , the average time T1/2 declined from 57.5 to 32.25 min ( p = 0.016 ) and average retention % GE dropped from 20.5 to 9.5 % ( p = 0.073 ) . Differences in the average values of weight , BMI , or % EWL between both groups were of no statistical significance ( p > 0.8 ) . Conclusions In the RA group , an increase in gastric emptying postoperatively was noted . Complications such as failure of stomach evacuation were not observed in the RA group . Our results suggest that even more radical resection of the pyloric antrum performed by LSG is possible without concerns of postoperative disorder of the stomach evacuation function Abstract Background Laparoscopic sleeve gastrectomy ( LSG ) has become a widely used primary bariatric surgery . As this is a restrictive procedure , calibrating bougie size is assumed to impact on both morbidity and weight loss . However , no prospect i ve studies have confirmed this hypothesis . The objective of this trial was to compare LSG outcomes using different calibrating bougie diameters . Material s and methods A r and omized controlled trial : 126 patients undergoing LSG were r and omized to either a 27-Fr ( group A ) or a 39-Fr ( group B ) calibrating bougie . Inclusion criteria were BMI 40–50 kg/m2 , aged 20–70 and absence of prior gastric surgery . All surgeries were performed by the same surgeon . Sample size was calculated to detect a six-point difference in percentage of excess weight loss ( % EWL ) at 1 year after surgery , considering an α error = 0.05 and a β error = 0.2 . The volume of resected stomach , morbidity and weight loss at 6 months and at 1 year after surgery were analyzed . Results Groups ( group A n = 62 , group B n = 64 ) were similar in BMI ( 44.3 vs. 43.5 ) , aged ( 41.9 vs. 42.2 ) and female percentage ( 87.1 vs. 84.3 % ) . A 1-year follow-up was achieved in 90.1 and 87.1 % , respectively . Two major complications occurred , one leak in each group ( 1.6 % ) . The volume of resected stomach was similar ( 426 vs. 402 ml , P = 0.71 ) , as well as 6 months % EWL ( 66.3 vs. 66.6 % ; P = 0.91 ) and 1 year % EWL ( 75.6 vs. 71.3 % , P = 0.21 ) . A 1-year % EWL higher than 50 was achieved in 96.5 % of patients in group A versus 85.2 % in group B ( P = 0.11 ) . Conclusions The use of different bougie diameters had no impact on the volume of resected stomach , morbidity or short-term weight loss after LSG , although a trend was seen toward better weight loss with the smaller bougie . A longer-lasting follow-up will be necessary to further assess differences Background Laparoscopic sleeve gastrectomy ( LSG ) is currently the leading bariatric procedure and targets , among other obesity classes , patients with BMI 30–35 kg/m2 , which are reaching alarming proportions . Methods Between February 2010 and August 2015 , data on 541 consecutive patients with BMI 30–35 kg/m2 undergoing LSG were prospect ively collected and analyzed . Results Mean age was 32 ± 8 years ( 13–65 ) and 419 ( 77.4 % ) were women . Preoperative weight was 92.0 ± 8.8 kg ( 65–121 ) and BMI was 32.6 ± 1.5 kg/m2 ( 30–35 ) . Comorbidities were detected in 210 ( 39 % ) patients . Operative time was 74 ± 12 min ( 40–110 ) and postoperative stay was 1.7 ± 0.22 days ( 1–3 ) . There were no deaths , leaks , abscesses or strictures and the rate of hemorrhage was 1.2 % . At 1 year , 98 % were followed and BMI decreased to 24.7 ± 1.6 , the percentage of total weight loss ( % TWL ) was 24.1 ± 4.7 while the percentage of excess BMI loss ( % E BMI L ) reached 106.1 ± 24.1 . At 5 years , 76 % of followed patients achieved a ≥50 % E BMI L. Conclusion With appropriate surgical expertise , LSG in patients with BMI 30–35 kg/m2 achieved excellent outcomes with a zero fistula rate Background Laparoscopic sleeve gastrectomy ( LSG ) is an emerging surgical technique with encouraging results . The objective of this study is to report surgical results after 1,000 consecutive LSG cases as a st and -alone procedure for morbid obesity during a 3-year follow-up . Methods Data were obtained by review of our prospect ively maintained data base , patients ’ clinical charts , and phone interview of all patients who underwent LSG in our institution from December 2005 to February 2010 . Results There were 773 ( 77.3 % ) women whose preoperative age and BMI was 36.9 ± 11.5 years and 37.4 ± 4.0 kg/m2 , respectively . The most common co-morbid conditions were insulin resistance 55.1 % , dyslipidemia 45.5 % , arterial hypertension 23.1 % , hypothyroidism 15.4 % and non-alcoholic fatty liver disease 12 % . Excess weight loss was as follows : 1 year 86.6 % , 2 years 84.1 % , and 3 years 84.5 % . Early and late complications occurred in 34 ( 3.4 % ) and 20 ( 2.0 % ) patients , respectively . Reoperation was required in seven ( 0.7 % ) patients . There was no mortality during follow-up . Conclusions LSG seems to be a safe and effective surgical technique for morbid obesity as a st and -alone procedure BACKGROUND Prompt management of laparoscopic sleeve gastrectomy ( LSG ) complications is essential in avoiding prolonged hospital stay and associated mortality . The value of routine computed tomography ( CT ) scan examination in early diagnosis of postoperative complications after LSG has not been studied . OBJECTIVES To prospect ively assess the impact of postoperative day ( POD ) 2 CT scan after LSG . SETTING Department of Minimally Invasive Digestive Surgery , Antoine-Beclere Hospital , AP-HP , Paris-Saclay University , France . METHODS Data were prospect ively gathered for 1000 patients undergoing single-incision LSG and POD 2 CT scan . Complications were identified and treatment modalities decided according to the severity of complications . Sensitivity , specificity , and positive and negative predictive values were calculated for the diagnosis of surgical complications on POD 2 CT scan . RESULTS Mean age was 40.1 years and median BMI 42.6 kg/m² . Early postoperative surgical complications occurred in 66 patients ( 6.6 % ) . Intraabdominal bleeding/hematoma occurred in 38 patients , with 3 requiring emergent reoperation on POD 1 . POD 2 CT scan detected this complication in 32 patients ( sensitivity : 91.4 % ) . Twenty-four ( 63.1 % ) patients were treated with relaparoscopy and drainage while 14 ( 36.9 % ) received conservative management . Postoperative transfusion was required in 7 patients . Twenty-eight patients suffered a gastric staple line leak , 13 ( sensitivity : 46.4 % ) detected on POD 2 CT scan . Three patients ( 10.7 % ) received pure surgical treatment , 16 ( 57.1 % ) combined relaparoscopy and endoscopic treatment , and 9 ( 32.2 % ) had pure endoscopic treatment . CONCLUSION POD 2 abdominal CT scan is an efficient diagnostic tool for detecting active bleeding/hematoma , but shows less impressive results with gastric staple line leak detection . A combination of clinical surveillance and early imaging allowed prompt management of complicated cases , avoiding further morbidity Purpose Laparoscopic sleeve gastrectomy ( SG ) has gained popularity and acceptance among bariatric surgeons , mainly due its low morbidity and mortality . The purpose of the present study was to evaluate the efficacy of SG on weight loss , and to determine the postoperative course , clinical presentation and treatment of complications after SG . Methods Between January 2006 and October 2012 , 153 consecutive patients underwent SG . All data were prospect ively collected in a computerized data base . Results This series comprised 119 females and 34 males with a median age of 46 years and a median preoperative BMI of 42.3 kg/m2 . The median EWL was 53.0 % after 18.4 months of follow-up . The median postoperative BMI was 33.3 kg/m2 ( range 19.7–56.1 kg/m2 ) . Eight patients ( 5.2 % ) required re-laparoscopy to manage postoperative hemorrhage ( 3.3 % ) and leakage ( 1.9 % ) . Neither abdominal drains nor postoperative contrast-swallow studies were successful in diagnosing hemorrhage or leaks in our patients . ConclusionS G is an effective procedure to achieve significant short-term weight loss . Clinical signs , such as tachycardia , pain , fever and hypotension , provide the best evidence of the presence of postoperative leakage or bleeding . An early diagnosis of these complications is the key to ensuring adequate treatment with immediate re-laparoscopy Background Leaks and bleeding are serious postoperative complications after a sleeve gastrectomy ( SG ) . The objective of the present study was to evaluate the costs of leaks and bleeding after SG . Methods A retrospective analysis was conducted of a prospect i ve cohort of primary SGs between August 2006 and September 2013 in a bariatric center . All SGs were performed consistently without reinforcement of the staple line . Abscesses adjacent to the staple line were also regarded as leaks . Data were collected on all diagnostic and therapeutic measures necessary to manage leaks or bleeding , days of hospitalization and parenteral feeding , number of blood products , antibiotics , and additional outpatient department visits . Results One thous and two hundred sixty one patients underwent a SG . Leaks occurred in 32 ( 2.5 % ) and bleeding in 27 ( 2.1 % ) patients . Median additional costs for leaks were € 9284 ( range € 1748–125,684 ) and € 4267 ( range € 1524–40,022 ) for bleeding . Prolonged hospitalization in the ward and ICU accounted for the majority of costs , 50.3 and 31.4 % , respectively , for leaks and 42.0 and 34.8 % for bleeding . Conclusions These data provide insight into the costs of major complications after SG . A wide range is seen especially due to prolonged hospitalization in the ward and ICU . High costs are an additional argument to reduce complication rate . These data should be considered when analyzing the cost-effectiveness of staple line reinforcement Background Laparoscopic sleeve gastrectomy ( LSG ) is becoming one of the most popular bariatric procedures because of its short operative time , good resolution of comorbidities , excellent weight loss , and low complications rate . However , the safety of LSG as a day-surgery procedure has not yet been widely documented . Methods A retrospective analysis of a prospect ively collected bariatric data base , in a single institution , between August 2012 and February 2015 , yielded 980 patients who underwent LSG ; 328 patients ( 33.5 % ) responded to established criteria and were operated on a 1-day surgery basis ( length of stay < 12 h ) . Results There were 258 ( 78 % ) primary LSG and 70 revisional LSG ( 22 % ) performed on 284 females and 44 males , with a mean age ( ±SD ) of 38 ± 9 years . Mean ( ±SD ) preoperative body mass index ( BMI ) was 45 ± 6 kg/m2 . Operative time was 68 ± 17 min ( mean ± SD ) . There were no deaths . A total of 322 patients ( 98.2 % ) were discharged home the day of surgery . There were 6 ( 1.8 % ) unplanned overnight hospitalization , and 28 patients ( 8.5 % ) were readmitted between days 1 and 30 . Most patients ( 25/34 , 73 % ) were hospitalized for minor problems , such as pain , nausea , and /or vomiting . There were two cases of ( 0.6 % ) gastric staple line leaks , three ( 0.9 % ) of intra-abdominal hematomas , two ( 0.6 % ) of pneumonia , one ( 0.3 % ) of acute pancreatitis , and one ( 0.3 % ) of urinary tract infection . All patients recovered well . Conclusions LSG can be performed as an outpatient procedure in selected patients , with acceptable results in terms of retention , readmission , and complication rates Background No r and omized comparative trials have presented long-term outcomes for laparoscopic sleeve gastrectomy ( LSG ) and laparoscopic Roux-en-Y gastric bypass ( LRYGB ) . The present study was design ed to compare the efficacy and safety of these two procedures . Methods From January 2007 to July 2008 , 64 eligible patients were r and omly assigned to LSG or LRYGB . During the 5-year follow-up , we compared morbidity rate , body mass index ( BMI ) , percent of excess weight loss ( % EWL ) , Moorehead-Ardelt ( M-A ) II quality of life , and resolution or improvement rate of obesity-related comorbidities between the groups . Results Both groups were matched with respect to age , gender , and BMI . Slightly more major complications were observed in patients undergoing LRYGB ( P > 0.05 ) . Weight loss was significantly better with LRYGB except during the first postoperative year . At 5 years , % EWL for LSG and LRYGB was 63.2 ± 24.5 % and 76.2 ± 21.7 % ( P = 0.02 ) , respectively . No statistical difference was observed in quality of life between the groups at all intervals ( P > 0.05 ) . At the last follow-up , most comorbidities in both groups were resolved or improved , with no difference between the groups ( P > 0.05 ) . Conclusion LRYGB and LSG are equally safe and effective in quality of life and improvement or resolution of comorbidities , and LRYGB possesses the superiority in terms of weight loss . Further studies are needed to evaluate micronutrient deficiencies of these procedures Background The main drawback of laparoscopic sleeve gastrectomy ( LSG ) is the severity of postoperative complications . Staple line reinforcement ( SLR ) is strongly advocated . The purpose of this study was to compare prospect ively and r and omly three different techniques of SLR during LSG . Methods From April 2010 to April 2011 , patients su bmi tted to LSG were r and omly selected for the following three different techniques of SLR : oversewing ( group A ) ; buttressed transection with a polyglycolide acid and trimethylene carbonate ( group B ) ; and staple-line roofing with a gelatin fibrin matrix ( group C ) . Primary endpoints were reinforcement operative time , incidence of postoperative staple-line bleeding , and leaks . Operative time was calculated as follows : oversewing time in group A ; positioning of polyglycolide acid and trimethylene carbonate over the stapler in group B ; and roofing of the entire staple line in group C. Results A total of 120 patients were enrolled in the study ( 82 women and 38 men ) . Mean age was 44.6 ± 9.2 ( range , 28–64 ) years . Mean preoperative body mass index was 47.2 ± 6.6 ( range , 40–66 ) kg/m² . Mean time for SLR was longer in group A ( 14.2 ± 4.2 ( range , 8–18 ) minutes ) compared with group B ( 2.4 ± 1.8 ( range , 1–4 ) minutes ) and group C ( 4.4 ± 1.6 ( range , 3–6 ) minutes ; P < 0.01 ) . Four major complications were observed ( 3.3 % ): one leak and one bleeding in group A ; one bleeding in group B ; and one leak in group C , with no significant differences between the groups . No mortality was observed . Conclusions SLR with either polyglycolide acid with trimethylene carbonate or gelatin fibrin matrix is faster compared with oversewing . No significant differences were observed regarding postoperative staple-line complications Objectives : In this study , we report long-term outcomes of high-risk , high- BMI ( body mass index ) patients who underwent laparoscopic sleeve gastrectomy ( LSG ) . Background : Short- and medium-term data appear to support the effectiveness of LSG , but long-term data to support its durability are sparse . Methods : A prospect i ve data base was review ed on all high-risk patients who underwent LSG as part of a staged approach for surgical treatment of severe obesity between January 2002 and February 2004 . We included only patients who did not proceed to second-stage surgery ( gastric bypass ) . Analyzed data included demographics , BMI , comorbidities , and surgical outcomes . All partial gastrectomies were performed using a 50F bougie . Results : Seventy-four patients underwent LSG , and follow-up data were available on 69 of 74 patients ( 93 % ) . The mean age was 50 years ( 25–78 ) and the mean number of co-morbidities was 9.6 . Perioperative mortality ( < 30 days ) was zero , and the incidence of short- and long-term postoperative complications was 15 % . The mean overall follow-up time period was 73 months ( 38–95 ) . Mean excess weight loss ( EWL ) at 72 , 84 , and 96 months after LSG was 52 % , 43 % , and 46 % , respectively , with an overall EWL of 48 % . The mean BMI decreased from 66 kg/m2(43–90 ) to 46 kg/m2 ( 22–73 ) . Seventy-seven percent of the diabetic patients showed improvement or remission of the disease . Conclusions : This study reports the longest follow-up of LSG patients thus far and supports the effectiveness , safety , and durability of laparoscopic sleeve gastrectomy as a definitive therapeutic option for severe obesity , even in high-risk , high- BMI patients Background Laparoscopic Sleeve Gastrectomy ( LSG ) is a relatively new procedure that is gaining wide acceptance . However , laparoscopic Roux-en-Y Gastric Bypass ( LRYGB ) remains one of the most commonly performed bariatric procedures with the best long-term results . There are few studies comparing LSG with LRYGB . The aim of this study is to compare the safety and outcome of LSG to LRYG in a single accredited center . Methods A retrospective analysis of data collected prospect ively on patients undergoing either LSG or LRYGB between January 2009 and December 2012 was performed . LSG was performed using 36Fr bougie , while LRYGB was perfromed with a 25-mm circular stapler . The primary outcomes included length of stay ( LOS ) , 30-day complication and readmission rates , and excess weight loss ( % EWL ) at 3 , 6 , 12 , and 24 months postoperatively . LSG patients were also divided into different categories based on BMI and their % EWL compared to LRYGB . Results A total of 885 patients were included in our analysis . 547 patients underwent LRYGB ( 61.8 % ) and 338 underwent LSG ( 38.2 % ) . Thirty-day complication and readmission rates for LRYGB and LSG were ( 1.5 and 5.1 % vs 0.6 and 0.3 % , respetively , p > 0.05 ) . % EWL for LRYGB was significantly higher than LSG at 3 , 6 , 12 , and 24 months . LSG with a BMI < 40 achieved a similar % EWL to LRYGB in the first 12 months . Conclusions LSG seems to have a better safety profile in the short-term compared to LRYGB . However , at 2 years , LRYGB patients achieved a significantly higher EWL compared to LSG patients . R and omized clinical trials are needed to better eluci date our findings BACKGROUND A growing body of evidence supports the laparoscopic sleeve gastrectomy ( LSG ) as a safe and effective procedure for sustained weight loss and amelioration of weight-related co-morbidities . Procedures performed in ambulatory surgery centers ( ASC ) can provide several advantages over hospital-based surgery . We present our results of 250 consecutive patients undergoing LSG in an ASC . The objective of this study was to assess the safety and efficacy of outpatient LSG in a freest and ing ASC . METHODS Data was collected prospect ively from 250 consecutive patients who underwent LSG at a freest and ing ASC . Patients were excluded from the ASC if they weighed>450 pounds , if anticipated operative time was>2 hours , if the patient had impaired mobility limiting early ambulation , or if there were medical problems requiring postoperative monitoring beyond 23 hours . Revisions were not included in this study . RESULTS Mean age was 47 years ( range , 23 - 74 yr ) . Mean preoperative body mass index ( BMI ) was 43 kg/m² ( 29 - 71 kg/m² ) . Mean operative time was 60 minutes ( 31 - 161 min ) . Mean recovery room time was 131 minutes ( 30 - 385 min ) . Mean percent excess weight loss ( % EWL ) was 60 % at 1 year and 63 % at 2 years . Nine patients ( 3.6 % ) were readmitted within 30 days . Two patients ( .8 % ) were transferred from the ASC to a hospital . There was 1 staple line leak ( .4 % ) . There were no open conversions and no deaths . CONCLUSIONS LSG can be performed safely in a freest and ing ASC in select patients with outcomes comparable to the inpatient st and ard . Additional studies are needed to formulate selection criteria and guidelines to maximize patient safety and outcomes Background Laparoscopic sleeve gastrectomy ( LSG ) has been gaining acceptance because it has shown good short- and mid-term results as a single procedure for morbid obesity . The aim of this study was to compare short- and mid-term results between laparoscopic Roux-en-Y gastric bypass ( LRYGB ) and LSG . Methods Observational retrospective study from a prospect i ve data base of patients undergoing LRYGB and LSG between 2004 and 2011 , where 249 patients ( mean age 44.7 years ) were included . Patients were followed at 1 , 3 , 6 , 12 , and 18 months , and annually thereafter . Short- and mid-term weight loss , comorbidity improvement or resolution , postoperative complications , re- interventions , and mortality were evaluated . Results One hundred thirty-five LRYGB and 114 LSG were included . Significant statistical differences between LRYGB and LSG were found in operative time ( 153 vs. 93 min . p < 0.001 ) , minor postoperative complications ( 21.5 % vs. 4.4 % , p = 0.005 ) , blood transfusions ( 8.8 % vs. 1.7 % , p = 0.015 ) , and length of hospital stay ( 4 vs. 3 days , p < 0.001 ) . There were no differences regarding major complications and re- interventions . There was no surgery-related mortality . The percentage of excess weight loss up to 4 years was similar in both groups ( 66 ± 13.7 vs. 65 ± 14.9 % ) . Both techniques showed similar results in comorbidities improvement or resolution at 1 year . Conclusions There is a similar short- and mid-term weight loss and 1-year comorbidity improvement or resolution between LRYGB and LSG , although minor complication rate is higher for LRYGB . Results of LSG as a single procedure need to be confirmed after a long-term follow-up Background The sleeve gastrectomy is an example of minimally invasive surgery . It is important to determine the critical steps of the procedure in order to reduce complications and increase safety and efficiency . Objective The aim of this study was to detect the key elements of the sleeve gastrectomy and find the potential hazard zones of the procedure . Setting Bariatric department of a large teaching hospital in the Netherl and s. Methods A prospect i ve clinical observation study was performed including 60 sleeve gastrectomy procedures . An expert panel determined the key steps , and two experts assessed the procedures systematic ally for technical errors according to the principles of Observational Clinical Human Reliability Assessment ( OCHRA ) . Results A total of 213 technical errors have been made , and the majority were made during mobilization of the greater curvature and during stapling of the stomach . In 44.6 % , errors had consequences and 96 additional actions were performed . There was a significant correlation between errors during opening of the lesser sac and postoperative complications , and between repositioning of the stapler and postoperative complications . Conclusions In this study , the 13 key steps of the SG were defined , and OCHRA was considered a valuable assessment tool for surgical performance and potential hazard zones . Most consequential errors are made during dissection of the greater curvature and during stapling of the stomach . Errors during the start of mobilization of the greater curvature and repositioning of the stapler lead to longer duration of the procedure and are associated with a higher risk of postoperative complications AIM To compare the mid-term outcomes of laparoscopic sleeve gastrectomy ( LSG ) and laparoscopic Roux-en-Y gastric bypass ( LRYGB ) in obese Korean patients . METHODS All consecutive patients who underwent either LSG or LRYGB with primary to treat morbid obesity between January 2011 and December 2012 were retrospectively review ed . Patients with a body mass index ( BMI ) ≥ 30 kg/m(2 ) with inadequately controlled obesity-related comorbidities ( e.g. , diabetes , obstructive sleep apnea , hypertension , or obesity-related arthropathy ) or BMI ≥ 35 kg/m(2 ) were considered for bariatric surgery according to the International Federation for the Surgery of Obesity-Asia Pacific Chapter Consensus statements in 2011 . The decision regarding the procedure type was made on an individual basis following extensive discussion with the patient about the specific risks associated with each procedure . All operative procedures were performed laparoscopically by a single surgeon experienced in upper gastrointestinal surgeries . Baseline demographics , perioperative surgical outcomes , and postoperative anthropometric data from a prospect ively established data base were thoroughly review ed and compared between the two surgical approaches . RESULTS One hundred four patients underwent LSG , and 236 underwent LRYGB . Preoperative BMI in the LSG group was significantly higher than that of the LRYGB group ( 38.6 kg/m(2 ) vs 37.2 kg/m(2 ) , P = 0.024 ) . Patients with diabetes were more prevalent in the LRYGB group ( 18.3 % vs 35.6 % , P = 0.001 ) . Operating time and hospital stay were significantly shorter in the LSG group compared with the LRYGB group ( 100 min vs 130 min , P < 0.001 ; 1 d vs 2 d , P = 0.003 ) , but the incidence of perioperative complications was similar between the groups ( P = 0.351 ) . The mean percentage of excess weight loss ( % EWL ) was 71.2 % for LRYGB , while it was 63.5 % for LSG , at mean follow-up periods of 18.0 and 21.0 mo , respectively ( P = 0.073 ) . The % EWL at 1 , 3 , 6 , 12 , 18 , 24 , and 36 mo was equivalent between the groups . Four patients required surgical revision after LSG ( 4.8 % ) , while revision was only required in one case following LRYGB ( 0.4 % ; P = 0.011 ) . CONCLUSION Both LSG and LRYGB are effective procedures that induce comparable weight loss in the mid-term and similar surgical risks , except for the higher revision rate after LSG BACKGROUND Our objective was to ascertain procedure-related morbidity among laparoscopic Roux-en-Y gastric bypass ( LRYGB ) , laparoscopic sleeve gastrectomy ( LSG ) , and laparoscopic adjustable gastric b and ing ( LAGB ) patients . These are the 3 most common bariatric procedures performed worldwide . We review ed our experience since the introduction of LSG and compared the procedure-related morbidity among all 3 procedures . STUDY DESIGN We conducted a retrospective review of a prospect ively collected data base of all morbidly obese patients who underwent bariatric surgery between the years 2005 and 2011 . We identified and compared complications , mortality , readmissions , and reoperations in patients who underwent LRYGB , LAGB , and LSG . RESULTS A total of 2,199 bariatric procedures were performed during this period of time . Of those procedures , 1,327 were LRYGB , 619 were LSG , and 253 were LAGB . Perioperative mortality was not applicable for all 3 procedures . The leak rate was 0.5 % for LRYGB and 0.3 % for LSG , and was not applicable for LAGB . The average number of readmissions postoperatively was less than 2 times for all 3 procedures : LRYGB 1.96 times , LSG 1.49 times , and LAGB 1.54 times . The percentages of procedures requiring reoperations due to complications or failures were 14.6 % in the LAGB group , 6.6 % in the LRYGB group , and 1.8 % in the LSG group . CONCLUSIONS In short- and mid-term follow-up , LSG appears to have the lowest procedure-related morbidity when compared with LRYGB and LAGB Background Fistula is the most fearsome complication after sleeve gastrectomy . The outcome depends on early and timely diagnosis . C-reactive protein ( CRP ) and procalcitonin ( PCT ) have not been extensively evaluated in this context . Objective This study aim ed to evaluate the interest of C-reactive protein ( CRP ) and procalcitonin ( PCT ) assay for the early detection of gastric fistula after sleeve gastrectomy and to study the PCT as an adjunctive marker to the CRP . Setting Private Practice . Patients and methods This is a retrospective analysis of data collected prospect ively . This study was carried out in 97 patients who underwent sleeve gastrectomy between January 2011 and December 2012 . The fistula is an abnormal connection between two organs . An abscess is a collection of pus . Results The rate of postoperative complications ( fistulas and abscesses ) was 7.2 % . The incidence of fistula was 2 % and the incidence of abscess was 5 % . Both CRP and PCT were significantly higher in patients with postoperative fistula or abscess . Mean CRP was 61.3 mg/l in patients without complications and 161.3 mg/l in case of complications ( p = 0.02 ) . Mean postoperative PCT was 0.062 ng/ml in uncomplicated patients versus 0.108 mg/l in those with complications ( p = 0.0006 ) . CRP and PCT measured during the postoperative period were correlated with the occurrence of postoperative complications . Conclusion Early detection of fistula or abscess after sleeve gastrectomy simplifies the management of these complications . While the ideal biomarker of infection does not yet exist , this study shows that clinical observations in association with CRP and PCT measurements could be of help for the early detection of septic complications after sleeve gastrectomy The number of laparoscopic bariatric procedures being performed in the USA has increased dramatically in the past decade . Because of limited health-care re sources , hospital administrators and insurance carriers are placing emphasis on length of stay and patient outcomes . The goal of this study was to evaluate the feasibility and safety of a clinical pathway in managing patients undergoing bariatric surgery in a Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program ( MBSAQIP ) accredited center . The setting was a university hospital in USA . A retrospective analysis of data collected prospect ively on patients undergoing bariatric surgery at St Luke ’s University was performed . Patients included underwent either a laparoscopic Roux-en-Y gastric Bypass ( LRYGB ) or laparoscopic sleeve gastrectomy ( LSG ) . Patients were subjected to a clinical protocol and discharged when discharge criteria were met . The primary outcomes were length of stay , 30 day readmission , complication , and reoperation rates . A cost analysis of the savings accrued was also performed . Two hundred twenty-nine patients were included in our analysis ( 80.4 % females and 19.6 % males ) . Seventy-one patients ( 31 % ) underwent LSG , and 158 patients ( 69 % ) underwent LRYGB . The average length of stay was 32.45 h ( range 24–72 h ) . The 30-day readmission rate was 3.0 % ( 7/229 patients ) . The 30 day complication rate ( including intervention , reintubation , and reoperation ) was 2.6 % ( 6/229 ) . The 30 day mortality rate was 0 . The average prospect i ve cost savings were $ 2,016 and $ 1,209 per LRYGB and LSG patient , respectively . Our bariatric surgery clinical protocol is feasible and safe with substantial prospect i ve cost savings at St Luke ’s University and Health Network . Patients subjected to our protocol have low readmission and complication rates . Further studies are needed to fully eluci date the benefit of this innovative new protocol in bariatric surgery INTRODUCTION Among the surgical procedures for treatment of morbid obesity , laparoscopic sleeve gastrectomy has known widespread diffusion in the last years , although it is not free from significant morbidity rates . Aim of this work is to evaluate the incidence of Helicobacter pylori ( HP ) infection on the postoperative outcome of patients undergoing laparoscopic sleeve gastrectomy . METHODS Between January 2008 and December 2013 , 184 patients ( 65 males , 119 females ) , mean age 35.8 ± 5.7 years , affected with morbid obesity , mean BMI 46.6 ± 6.7 , underwent laparoscopic sleeve gastrectomy . All the specimens at the end of the operation were analysed by the same pathologist . Histological grading was based on the Sidney classification . RESULTS Seventy-two of the patients ( 39.1 % ) were HP positive , while 112 ( 60.9 % ) were negative . No significant differences were observed between the HP+ and HP- group in terms of age , sex , weight , BMI , incidence of comorbidities and duration of follow-up . All the operations were completed via laparoscopic approach . No mortality was observed . Postoperative complications occurred in 5 patients ( 2.7 % ) : three leaks ( 1.6 % ) , all in the HP- group and two bleedings ( 1.1 % ) , one in the HP+ and one in the HP- group . In two cases a reintervention was necessary . No significant differences were observed in the morbidity rates between the two groups . Overall mean excess weight loss at 6 months , 12 months and 24 months was respectively 47.4 ± 11.3 % , 61.1 ± 12.4 % and 68.4 ± 13.5 % , with no significant differences between the HP+ and HP- groups . CONCLUSIONS HP infection seems not to influence postoperative outcome of patients operated of laparoscopic sleeve gastrectomy BACKGROUND Reinforcement of the staple line in laparoscopic sleeve gastrectomy ( LSG ) is a practice that leads to less morbidity , but equivocal results have been reported in the literature . MATERIAL S AND METHODS This is a prospect i ve r and omized study comparing two groups of patients who underwent LSG . In one group LSG was performed with a running absorbable suture placement at the staple line . In the other group the running suture was not placed . General data of the patients , as well as intraoperative and postoperative data , were gathered and statistically analyzed . RESULTS Overall , 146 patients were subjected to LSG . In 84 patients a running suture was placed , and in 62 patients no suture was placed . No significant differences were found between the two groups in demographic data . No significant differences were found also in the intraoperative data , such as number of trocars , number and type of cartridges , drain placement , and operative time ( 45±21 versus 40±20 minutes , respectively ; P<.05 ) . Intraoperative complications were significantly more in the group with the suture placement ( 33.3 % versus 16.1 % , respectively ; P<.05 ) . Hematomas developed intraoperatively in more patients after the placement of the running suture ( 9.5 % versus 0.0 % , respectively ; P<.05 ) . Postoperatively , there was no significant difference in morbidity between the two groups ( 8.3 % versus 9.7 % , respectively ; P>.05 ) . CONCLUSIONS After this r and omized study , final conclusions about the efficacy of this running suture to the staple line can not be made . To the contrary , problems seem to exist after such reinforcement of the staple line , such as hematomas . Dealing with possible leaks and hemorrhage of the staple line is also problematic after placement of the running suture Background Few reports have compared laparoscopic sleeve gastrectomy ( LSG ) to laparoscopic Roux-en-Y procedure ( LRNY ) . This study aims at comparing the 5-year follow-up results of mini gastric bypass ( MGB or omega gastric bypass ( OGB ) ) and LSG in terms of weight loss , weight regain , complications , and resolution of co-morbidities . Methods A retrospective analysis of the prospect ively collected data base was done from the start of our bariatric practice from February 2007 to August 2008 ( minimum 5-year follow-up ) . During this period , 118 patients underwent LSG . These patients were matched in age , gender , preoperative weight , and BMI to 104 patients who underwent MGB in the same time period . The results were compared . Results Follow-up was achieved in 72 MGB vs 76 LSG patients up to 5 years . The mean BMI for the MGB and LSG group was 44 ± 3.1 and 42 ± 5.2 kg/m2 , respectively ( P < 0.001 ) . The average percentage of excess weight loss ( % EWL ) for MGB vs LSG was 63 vs 69 % at 1 year and 68 vs 51.2 % at 5 years ( P = 0.166 ) , respectively . Post-op gastro-esophageal reflux disease ( GERD ) was seen in 2.8 % MGB patients and marginal ulcer was diagnosed in 1 MGB patient ( 1.4 % ) . GERD was seen in 21 % post-LSG patients . Conclusions Both MGB and LSG are safe , short , and simple operations . Weight loss is similar in MGB and LSG in the first years , but lesser % EWL with LSG at 5 years ( 68 % in MGB vs 51 % in LSG ) . Post-op GERD is more common after LSG BACKGROUND Although laparoscopic sleeve gastrectomy ( LSG ) was initially described as the first step of a 2-stage procedure for high-risk patients requiring laparoscopic Roux-en-Y gastric bypass ( LRYGB ) , it is now being used as a single-stage procedure . Experience with laparoscopic bariatric surgery is growing , such that LRYGB is increasingly feasible for patients with body mass index ( BMI ) ≥ 50 kg/m² . Nevertheless , outcomes for such category of patients following LSG and LRYGB are lacking . OBJECTIVE To compare weight loss and changes in obesity related co-morbidities at one year following LSG with LRYGB in patients with BMI ≥ 50 kg/m² . SETTING S The prospect i ve data base of a single surgery university center was queried for clinical and other relevant data . METHODS From January 2004 to January 2013 , 74 and 285 patients underwent LSG or LRYGB with a BMI ≥ 50 kg/m² . At one year , rate of follow-up was 92.8 % . Success of surgery was defined as % of excess weight loss (%EWL)≥ 50 % at one year . Logistic regression was used to compute odds ratio ( OR ) to evaluate the success at one year of surgery . RESULTS LSG ( N = 74 ) and LGBP ( N = 285 ) groups did not differ for initial BMI ( 57.2 ± 7.1 versus 56.7 ± 5.5 kg/m² ; P = .52 ) , % of female ( 64.6 % versus 73.7 % , P = .13 ) or major adverse postoperative events ( 5.7 % versus 6.7 % ; P = .85 ) . At one year , the mean percentage of weight loss ( % ) ( 22.0 ± 7.6 versus 30.3 ± 7.4 ; P < .0001 ) and percentage of excess weight loss ( % ) ( 40.2 ± 15.2 versus 55.0 ± 14.6 ; P < .0001 ) and rates of remission of diabetes ( 47.5 % versus 70.7 % ; P = .01 ) were greater in the LGBP than LSG group . In multivariate analyses ( OR ) , LSG was an independent factor of failure of weight loss ( .12 ; P < .0001 ) CONCLUSION : After 1 year of follow-up in patients with a BMI ≥ 50 kg/m² , LRYGB provides better weight loss and resolution in diabetes than LSG with similar postoperative morbidity . Further long-term studies are needed to confirm these results INTRODUCTION Laparoscopic sleeve gastrectomy ( LSG ) is a popular bariatric procedure with a low complication rate . Serious complications after LSG include gastric leak and staple line bleeding . In order to reduce these complications , staple line reinforcement has been practice d variably by many surgeons . There is no conclusive evidence to suggest that routine oversewing of the staple line or reinforcement with buttressing material after LSG decreases these complications . We therefore undertook a prospect i ve r and omized controlled trial to evaluate the impact of oversewing of the staple line in preventing complications after LSG . PATIENTS AND METHODS Sixty patients undergoing LSG were r and omly allocated to two groups . In Group A , the entire staple line was reinforced with continuous suturing , and in Group B , no reinforcement was used . Thirty patients were enrolled in each group . Indications for this procedure were morbidly obese ( body mass index ≥40 kg/m(2 ) ) or severely obese ( body mass index ≥35 kg/m(2 ) ) patients with comorbidities including type 2 diabetes mellitus , hypertension , sleep apnea , and osteoarthritis . Complications including gastric leak , bleeding , and stricture were recorded . RESULTS The demographic parameters were comparable in the two groups . Two cases of early gastric leak occurred in Group B and none in Group A. There was no case of staple line bleeding or stricture in either group , although 1 patient in Group B had bleeding from the omentum that required re-operation . The overall surgical complication rate was 5 % . The mean operative time in Group A ( 139±10 minutes ) was significantly greater than in Group B ( 117±19 minutes ) ( P=.02 ) . CONCLUSIONS Oversewing of the staple line may lead to reduction in leak rate , although a larger study is required to reach a definitive conclusion . The incidence of staple line bleeding can be minimized by following meticulous technique and adequate compression time after closure of the stapler rather than placing undue emphasis on oversewing and expensive buttressing material Background This is a 2-year study to evaluate the feasibility ; outcomes in terms of postoperative pain , weight loss , and complication rates ; and cosmesis of the single-incision sleeve gastrectomy versus the conventional multiport sleeve gastrectomy . Methods A prospect i ve comparative analysis was done in 300 patients in each arm who underwent laparoscopic sleeve gastrectomy and single-incision sleeve gastrectomy from September 2009 till January 2012 . Both groups were matched for age and BMI . Postoperative pain scoring was done using visual analogue scale . Outcomes in terms of pain score , scar satisfaction score , excess weight loss , resolution of co-morbidities , and complications were compared in both groups at the end of 6 months , 1 year , and 2 years . Results Female patients preferred to undergo single-incision sleeve gastrectomy . Operating time and intraoperative blood loss were comparable in both groups . Visual analogue scale ( VAS ) scoring revealed lesser postoperative pain in the single-incision group . Excess weight loss and resolution of co-morbidities were also comparable in both groups at 6 months , 1 year , and 2 years . Incisional hernia was seen in 3 patients ( 1 % ) in the single-incision group . Leak rate was comparable . Cosmetic satisfaction was superior in patients who underwent single-incision surgery . Conclusions Surgical outcomes are comparable in both groups at the end of 2 years . The myth of high long-term incisional hernia rate after single-incision surgery has been dispelled . Single-incision surgery is less painful with better cosmesis . It has come of age and should no longer be considered as an experimental procedure ABSTRACT Introduction : Although its excellent results , laparoscopic sleeve gastrectomy ( LSG ) presents major complications ranging from 0 % to 29 % . Among them , the staple line leak presents an incidence varying from 0 % to 7 % . Many trials debated about different solutions in order to reduce leaks ’ incidence . No author has investigated the role of gastric decompression in the prevention of this complication . Aim of our work is to evaluate if this procedure can play a role in avoiding the occurrence of staple line leaks after LSG . Material s and Methods : Between January 2008 and November 2012 , 145 patients were prospect ively and r and omly included in the study . Seventy patients composed the group A , whose operations were completed with placement of nasogastric tube ; the other 75 patients were included in the group B , in which no nasogastric tube was placed . Results : No statistical differences were observed between group A and group B regarding gender distribution , age , weight , and BMI . No intraoperative complications and no conversion occurred in both groups . Intraoperative blood loss ( 50.1 ± 42.3 vs. 52.5 ± 37.6 ml , respectively ) and operative time ( 65.4 ± 25.5 vs. 62.6 ± 27.8 min , respectively ) were comparable between the two groups ( p : NS ) . One staple line leak ( 1.4 % ) occurred on 6th postoperative day in group A patients . No leak was observed in group B patients . Postoperative hospital stay was significantly longer in group A vs. group B patients ( 7.6 ± 3.4 vs. 6.2 ± 3.1 days , respectively , p : 0.04 ) . Conclusions : Routine placement of nasogastric tube in patients operated of LSG seems not useful in reducing leaks ’ incidence HYPOTHESIS The use of staple-line reinforcement sleeves during laparoscopic gastric bypass reduces staple-line bleeding , which may translate into a reduction in the rate of gastrointestinal hemorrhage . DESIGN Prospect i ve r and omized trial . SETTING University hospital . PATIENTS AND INTERVENTIONS Thirty-four patients undergoing laparoscopic gastric bypass were r and omly assigned to receive either no reinforcement ( control group , n = 17 ) or reinforcement of the staple line with glycolic copolymer sleeves ( treatment group , n = 17 ) . MAIN OUTCOME MEASURES Demographic data , the number of stapler loads used , the number of staple-line bleeding sites , the amount of blood loss , the length of time required to obtain hemostasis of the staple lines , operative time , intraoperative and postoperative complications , and serial hemoglobin levels . RESULTS The mean number of stapler loads used was similar between groups . The mean number of staple-line bleeding sites was significantly fewer in the treatment group for division of gastric tissue ( 0.4 vs 2.5 bleeding sites ) , jejunal tissue ( 0.1 vs 0.6 bleeding site ) , and mesenteric tissue ( 0 vs 0.8 bleeding site ) . The mean blood loss was lower in the treatment group ( 84 vs 129 mL ) . Staple misfire occurred in 1 ( 0.7 % ) of 143 stapler loads used in the treatment group compared with 0 ( 0 % ) of 138 stapler loads used in the control group . The time to obtain staple-line hemostasis was shorter in the treatment group ( 1.2 vs 10.1 minutes ) . The total operative time was similar between groups . There was no mortality or postoperative leaks . One patient in the control group had postoperative gastrointestinal hemorrhage requiring blood transfusion and reoperation . There was no significant difference in the mean hemoglobin level between groups on the first postoperative day . CONCLUSIONS The use of glycolide copolymer staple-line reinforcement sleeves in patients undergoing laparoscopic gastric bypass is safe and significantly reduces staple-line bleeding sites and may reduce the incidence of gastrointestinal hemorrhage Introduction Although bariatric surgery is actually mainly performed laparoscopically , analgesic optimization continues being essential to reduce complications and to improve the patients ’ comfort . The aim of this study is to evaluate the postoperative pain after analgesia iv exclusively , or associated with epidural analgesia or port-sites infiltration with bupivacaine . Patients and methods A prospect i ve r and omized study of patients undergoing laparoscopic sleeve gastrectomy between 2012 and 2014 was performed . Patients were divided into three groups : Analgesia iv exclusively ( Group 1 ) , epidural analgesia + analgesia iv ( Group 2 ) and port-sites infiltration + analgesia iv ( Group 3 ) . Pain was quantified by means of a Visual Analogic Scale , and morphine rescue needs were determined 24 h after surgery . Results A total of 147 were included . Groups were comparable in age , gender and BMI . There were no differences in operation time , complications , mortality or hospital stay between groups . Median pain 24 h after surgery was 5 in Group 1 , 2.5 in Group 2 and 2 in Group 3 ( P = 0.01 ) , without statistically significant differences between Groups 2 and 3 . In Group 1 , morphine rescue was necessary in 16.3 % of the cases , 2 % in Group 2 and 2 % in Group 3 ( P = 0.014 ) , without statistically significant differences between Groups 2 and 3 . Conclusion Epidural analgesia and port-sites infiltration with bupivacaine , associated with analgesia iv , reduce the postoperative pain , when compared with analgesia iv exclusively . Clinical trials Clinical Trials.gov Identifier : NCT02662660 Importance Laparoscopic sleeve gastrectomy for treatment of morbid obesity has increased substantially despite the lack of long-term results compared with laparoscopic Roux-en-Y gastric bypass . Objective To determine whether laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass are equivalent for weight loss at 5 years in patients with morbid obesity . Design , Setting , and Participants The Sleeve vs Bypass ( SLEEVEPASS ) multicenter , multisurgeon , open-label , r and omized clinical equivalence trial was conducted from March 2008 until June 2010 in Finl and . The trial enrolled 240 morbidly obese patients aged 18 to 60 years , who were r and omly assigned to sleeve gastrectomy or gastric bypass with a 5-year follow-up period ( last follow-up , October 14 , 2015 ) . Interventions Laparoscopic sleeve gastrectomy ( n = 121 ) or laparoscopic Roux-en-Y gastric bypass ( n = 119 ) . Main Outcomes and Measures The primary end point was weight loss evaluated by percentage excess weight loss . Prespecified equivalence margins for the clinical significance of weight loss differences between gastric bypass and sleeve gastrectomy were −9 % to + 9 % excess weight loss . Secondary end points included resolution of comorbidities , improvement of quality of life ( QOL ) , all adverse events ( overall morbidity ) , and mortality . Results Among 240 patients r and omized ( mean age , 48 [ SD , 9 ] years ; mean baseline body mass index , 45.9 , [ SD , 6.0 ] ; 69.6 % women ) , 80.4 % completed the 5-year follow-up . At baseline , 42.1 % had type 2 diabetes , 34.6 % dyslipidemia , and 70.8 % hypertension . The estimated mean percentage excess weight loss at 5 years was 49 % ( 95 % CI , 45%-52 % ) after sleeve gastrectomy and 57 % ( 95 % CI , 53%-61 % ) after gastric bypass ( difference , 8.2 percentage units [ 95 % CI , 3.2%-13.2 % ] , higher in the gastric bypass group ) and did not meet criteria for equivalence . Complete or partial remission of type 2 diabetes was seen in 37 % ( n = 15/41 ) after sleeve gastrectomy and in 45 % ( n = 18/40 ) after gastric bypass ( P > .99 ) . Medication for dyslipidemia was discontinued in 47 % ( n = 14/30 ) after sleeve gastrectomy and 60 % ( n = 24/40 ) after gastric bypass ( P = .15 ) and for hypertension in 29 % ( n = 20/68 ) and 51 % ( n = 37/73 ) ( P = .02 ) , respectively . There was no statistically significant difference in QOL between groups ( P = .85 ) and no treatment-related mortality . At 5 years the overall morbidity rate was 19 % ( n = 23 ) for sleeve gastrectomy and 26 % ( n = 31 ) for gastric bypass ( P = .19 ) . Conclusions and Relevance Among patients with morbid obesity , use of laparoscopic sleeve gastrectomy compared with use of laparoscopic Roux-en-Y gastric bypass did not meet criteria for equivalence in terms of percentage excess weight loss at 5 years . Although gastric bypass compared with sleeve gastrectomy was associated with greater percentage excess weight loss at 5 years , the difference was not statistically significant , based on the prespecified equivalence margins . Trial Registration clinical trials.gov Identifier : BACKGROUND Surgery remains the most effective intervention for obesity and its comorbidities . However , the long-term efficacy of bariatric procedures is rarely reported . This study addresses operative trends , efficiency , and long-term outcomes from a large bariatric program . STUDY DESIGN Data were prospect ively collected on 3,460 patients undergoing 3,503 operations from January 2004 to March 2013 . Primary procedures included Roux-en-Y gastric bypass ( RY ; n = 2,966 ) , adjustable b and ( AB ; n = 352 ) , and sleeve gastrectomy ( SG ; n = 118 ) . There were 67 revisional procedures ( RP ) . Mean operative time , hospital length of stay , major 30-day morbidity/mortality , follow-up compliance , and weight loss per procedure at follow-up were recorded . RESULTS Mean operative times decreased to the following : RY , 53 minutes ; AB , 35 minutes ; SG , 46 minutes ; and RP , 71 minutes . Mean length of stay was reduced to the following : RY , 1.53 days ; AB , 0.97 days ; SG , 2.12 days ; and RP , 2.68 days . Major complications were mortality , 0.09 % ; leak , 0.51 % ; bleed , 2.37 % ; pneumonia , 0.63 % ; venous thromboembolism , 0.40 % ; and reoperation , 2.34 % . The complication rate was lowest for AB and highest for SG ( p < 0.05 ) . Adjustable b and was the initial procedure in 73 % of cases requiring RP . Follow-up compliance was 93 % at 1 year , 79 % at 3 years , 71 % at 5 years , and 33 % at 9 years . Adjustable b and offered significant weight loss at 1 and 3 years ( p < 0.0001 ) , but less than RY or SG ( p < 0.0001 ) . Excess weight loss was not significantly different between RY and SG at 1 year . Significant weight loss with RY persisted at 7 to 9 years ( p < 0.0001 ) . CONCLUSIONS Our bariatric program experienced an increase in SG and RP and a decrease in AB . Optimization of care reduced operative time and length of stay . All procedures achieved significant weight loss in the first year . Adjusted b and had the lowest morbidity , but inferior weight loss and greater need for revision . Long-term weight-loss data are only available for RY Background Sleeve gastrectomy is a common procedure in recent years for treatment of morbid obesity however leak from staple-line is its main challenging complication . Despite numerous studies regarding leak after sleeve gastrectomy , there is still no conclusion on reinforcement of staple-line in this procedure . The purpose of this study was to compare two methods of oversewing staple-line versus no reinforcement . Methods Resected stomachs of 30 patients undergoing laparoscopic sleeve gastrectomy were evaluated for bursting pressure immediately after extraction from the abdomen . Reinforcement technique was applied in r and om order to 3 segments of the staple-line on each specimen : continuous Lembert ’s sutures , continuous through- and -through sutures , and no reinforcement . Bursting pressure was determined by injection of methylene blue solution into lumen of resected stomach and recording pressure at which leakage occurs . Location of leak , intragastric pressure , and volume at first leak were recorded . Results Baseline characteristics of patients were similar in r and omized groups for order of reinforcement technique . Mean ischemia time of specimens was 17.4 ± 10.4 min . No leaks were observed in segments reinforced with Lembert ’s oversewing technique . The through- and -through reinforcement segments were first to leak in 21 out of 30 cases ( 70 % ) with mean leak pressure of 570 mmHg and mean leak volume of 399 ml . Leakage occurred in 9 segments ( 30 % ) with no reinforcement with a leak pressure of 329 mmHg and volume of 380 ml . Conclusions In vitro , Lembert ’s suture reinforcement technique on stapled human stomach is associated with less leakage rate in comparison to through- and -through reinforcement and non-reinforced staple-line BACKGROUND Laparoscopic sleeve gastrectomy ( LSG ) is gaining popularity worldwide as a definitive bariatric procedure . However , there are still some controversial issues associated with the technique , one of which is the size of the residual antrum . OBJECTIVES The aim of this prospect i ve r and omized trial is to study the effect of the size of the residual gastric antrum on the outcome of LSG . SETTING S University-affiliated hospital . METHODS Between November 2009 and August 2013 , 113 morbidly obese patients su bmi tted for LSG were r and omized into 2 groups , namely antral preserving-LSG ( AP-LSG ) and antral resecting-LSG ( AR-LSG ) , depending on the distance from the pylorus at which gastric division begins . In the AP-LSG group , the distance was 6 cm from the pylorus and included 58 patients , whereas the distance was 2 cm in the AR-LSG group and included 55 patients . The follow-up period was at least 12 months . Baseline and 6 and 12 month outcomes were analyzed including assessment s of the percent excess weight lost ( % EWL ) , reduction in BMI , morbidity , mortality , reoperations , quality of life , and co-morbidities . RESULTS Both groups were comparable regarding age , gender , body mass index ( BMI ) , and co-morbidities . There was one 30-day mortality , and there was no significant difference in the complication rate or early reoperations between the 2 groups . Weight loss was significant in both groups at 6 and 12 months . At 12 months , weight loss was greater in the AR-LSG than in the AP-LSG group , but with was no significant difference between the 2 groups at 12 months ( % EWL was 64.2 % in the AP-LSG group and 67.6 % in the AR-LSG group ; p>.05 ) . The resolution/improvement of co-morbidities , quality of life outcome and the overall prevalence of co-morbidities were similar . CONCLUSIONS LSG with or without antral preservation produces significant weight loss after surgery . The 2 procedures are equally effective regarding % EWL , morbidity , quality of life , and amelioration of co-morbidities BACKGROUND When performing sleeve gastrectomy , a bougie ( 32 to 60 French ) is used . We evaluated 2 different bougie sizes on early postoperative outcomes and long-term weight loss . METHODS A 1-year prospect i ve study was conducted on patients undergoing sleeve gastrectomy . In the first 6 months , patients had 32-French bougies ( Group 1 ) ; in the second 6 months , they had 36-French bougies ( Group 2 ) . RESULTS We evaluated 131 patients . No intraoperative complications or mortality occurred . Postoperatively , Group 1 ( n = 72 ) had a longer hospital stay ( 1.6 ± .8 vs 1.3 ± .5 days , P = .04 ) and used more Ondansetron for nausea than Group 2 ( n = 59 ) ( 6.7 ± 8.0 vs 5.3 ± 4.5 mg , P = .2 , respectively ) . Ten ( 14 % ) patients in Group 1 returned to the emergency department compared with 5 ( 9 % ) in Group 2 . One-year percent excess weight loss was similar ( 73.0 ± 20.6 % vs 71.1 ± 20.9 % , P = .73 , respectively ) . CONCLUSIONS The smaller bougie result ed in a longer hospital stay , with tendency toward increased nausea , more emergency department visits , and readmissions . Long-term weight loss was not affected BACKGROUND The prevalence of superobesity ( body mass index [ BMI ] ≥50 kg/m(2 ) ) has increased steadily during the past decade , and the most suitable surgical strategy for these patients is still controversial . Our objective was to test the hypothesis that in selected superobese patients , laparoscopic sleeve gastrectomy ( SG ) followed by laparoscopic duodenal switch ( DS ) might reduce the rate of postoperative complications and the need for the second step duodenal switch . The setting was a university hospital in France . METHODS A retrospective analysis was performed of a prospect i ve data base of 110 consecutive patients with a BMI of ≥50 kg/m(2 ) undergoing the staged approach and matched for age , gender , and BMI with 110 consecutive patients undergoing single-stage DS . The excess weight loss ( EWL ) , co-morbidity improvement , and incidence of postoperative complications were compared between the 2 groups . RESULTS One patient died in the staged strategy group ( mortality rate .9 % ) . The postoperative complication rate was 8.2 % in the staged strategy group ( 110 patients ) and 15.5 % in the single-stage DS group ( 110 patients ; P = 1 ) . Multivariate analysis showed that single-stage DS surgery is the only variable significantly associated with the occurrence of postoperative complications ( odds ratio 2.36 ; 95 % confidence interval 1.001 - 5.61 ) . In the staged strategy group , at a mean follow-up of 36.4 ± 13 months , 39 patients ( 35.5 % ) required the second-stage procedure . The mean % EWL was 50.8 % ± 17.5 % for SG alone ( 35 % failed to maintain 50 % EWL after SG ) , 61.5 % ± 19.3 % for the staged strategy , 72.7 % ± 14.1 % for 2-step DS ( 3.3 % failed to maintain 50 % EWL after 2-step DS ) , and 73.3 % ± 17.6 % for single-stage DS ( 7.3 % failed to maintain 50 % EWL after single-stage DS ) . CONCLUSIONS At 3 years of follow-up , staged DS surgery avoided biliopancreatic diversion in 72.7 % of the patients . Single-stage DS increases the risk of postoperative complications but not of anastomotic leak BACKGROUND Preliminary results of a new bariatric surgery program in a VA Medical Center using laparoscopic sleeve gastrectomy ( LSG ) . METHODS Prospect i ve review of the first 50 patients who underwent LSG . Percentage change in body mass index ( BMI ) , comorbidities , serum glucose , glycosylated hemoglobin ( HbA1c ) , lipid profiles , and medications were recorded . RESULTS Mean age was 52 years . Average BMI was 46 kg/m(2 ) . There were no mortalities or staple line leaks . The percentage excess BMI loss was 47 % and 54 % at 6 and 12 months , respectively . After 6 months , fasting glucose level decreased from 127 to 93 mg/dL , and mean glycosylated hemoglobin decreased from 6.8 % to 5.7 % . At 1-year follow-up evaluation , serum cholesterol decreased from 182 to 168 mg/dL , mean triglycerides from 179 to 93 mg/dL , low-density lipoprotein from 110 to 94 mg/dL , and high-density lipoprotein increased from 42 to 50 mg/dL. CONCLUSIONS Laparoscopic sleeve gastrectomy is safe and effective for morbidly obese VA patients and result ed in significant discontinuation of medication for hypertension , diabetes and hyperlipidemia Background Laparoscopic sleeve gastrectomy ( LSG ) has gained worldwide popularity in recent years . Hemorrhagic complications ( HC ) are usually the result of stapler line bleeding and are probably underreported . The previous incidence of HC in our department including minor bleeding and late hematomas was 15.0 % . The objective of this study is to assess the impact of stapler line reinforcement ( SLR ) and intraoperative blood pressure control on HC after LSG . Methods Between February 2013 and March 2014 , patients who were admitted to our department for LSG were r and omly assigned to one of three arms : stapler line application of biologic glue — Evicel ™ ( E ) , over suture of the stapler line ( S ) or control ( C ) . Surgical technique in all arms included blood pressure elevation to 140 mmHg before termination of the procedure . Data is presented as mean ± SD or median ( IQR 25–75 ) . Results One hundred sixty-five patients were r and omized : 49 to E , 49 to S , and 67 to C. There were no demographic differences between arms . Operative time was significantly longer in S than in E and C arms ( 74 ± 21 vs. 64 ± 23 and 54 ± 19 min , respectively ) . ∆Hb was significantly lower in the S group . Packed cells were used in two from E and one from C arms . Late infected hematoma occurred in three ( 1.8 % ) patients : one from E and two from C arms . Leak rate was 1.2 % : one from S and one from C arms . LOS was the same . No patients were re-operated due to bleeding . Conclusions In this r and omized trial , routine elevation of systolic blood pressure to 140 mmHg and over suture of the staple line in LSG minimized HC , with reasonable prolongation of the procedure Background The objective of this study was to evaluate the effect of antral resection on weight loss and complications after laparoscopic sleeve gastrectomy ( LSG ) . Methods This was a retrospective study of the prospect ively collected data of patients who underwent LSG at Jordan University Hospital from February 2011 to February 2012 . Patients were divided into two groups based on antral resection : group A underwent a 6-cm antral resection , and group B underwent a 2-cm antral resection . The percentage of excess weight loss ( % EWL ) was calculated at 3 , 6 , 12 , and 24 months postoperatively . Results One hundred and ten patients were included in the study , all of whom completed at least 24 months of follow-up ( mean follow-up , 33 months ) . Their mean body mass index was 46.1 ± 7.9 kg/m2 . In group A , the mean % EWL was 38.1 ± 14.1 , 54.9 ± 19.9 , 65.6 ± 22.8 , and 66.8 ± 28.4 % at 3 , 6 , 12 , and 24 months , respectively . However , in group B , the mean % EWL was 42.1 ± 13.4 , 63.8 ± 19.8 , 80.0 ± 22.1 , and 81.5 ± 22.9 % at 3 , 6 , 12 , and 24 months , respectively . Patients in group B experienced statistically significant greater weight loss than patients in group A. Statistically significant greater weight regain was seen in group A. Group A had a higher incidence of reflux symptoms ( six patients ; 11 % ) than group B ( four patients ; 7.1 % ) . Conclusions Radical antral resection in association with LSG safely potentiates the restrictive effect achieved and may result in greater and better maintained weight loss Staple line leakage and bleeding are worrisome complications of laparoscopic sleeve gastrectomy ( LSG ) . Solutions such as buttressing , oversewing or roofing the staple line with gelatin matrix have been proposed with controversial results . Because the use of fibrin sealant has shown a possible benefit in reducing the reoperation rate due to early complication in patients ( pts ) undergoing laparoscopic Roux-en-Y gastric bypass ( LRYGBP ) , this solution has been tested in 100 consecutive pts undergoing LSG . A clinical trial has been performed on 100 consecutive pts . Exclusion criteria from the study were considered ASA IV pts , treated or untreated malignancies at any stage , steroids or FANS assumption , previous sovramesocolic surgery and conversion to open surgery . All pts were r and omized to receive ( group A , 50 pts ) or to not receive ( group B , 50 pts ) 4 ml of human fibrin sealant ( Tisseel ™ , Baxter ® Deerfield , IL , USA ) sprayed along the suture line . Primary endpoint was the incidence of postoperative complications : leaks , bleeding of the staple line or stenosis of the gastric remnant . Significance was assigned at a p level < 0.05 . By considering pts in group A vs. pts in group B our results shown no significant difference in fistulas or strictures occurrence ( p = 0.2 ) . Bleeding was significantly higher in patients not sprayed with sealant ( group A vs. group B , 1/7 , p = 0.03 ) . This r and omized trial has so far shown the use of fibrin sealant in LSG to significantly reduce postoperative bleeding . Although a trend in reducing leak occurrence emerges , it does not reach statistical significance |
742 | 31,506,067 | Including only higher- quality studies had little effect on findings , with heterogeneity remaining high ( I2 statistic > 50 % ) .
Significant gestational blood pressure and heart rate changes occur that should be taken into account when assessing pregnant women .
Commonly taught substantial decreases in blood pressure mid-pregnancy were not seen and heart rate increases were lower than previously thought . | Current reference ranges for blood pressure and heart rate throughout pregnancy have a poor evidence base .
This is a systematic review and meta- analysis . | We evaluated the influence of maternal pre-pregnancy body mass index ( BMI ) , based on reported pre-pregnancy weight and height , on blood pressure ( BP ) levels during pregnancy by using information from a prospect i ve cohort of 1733 women recruited before 20 weeks ' gestation . Maternal antenatal BP values were abstract ed from medical records , and we evaluated the mean BP differences according to BMI group in regression models , using generalised estimating equations to account for repeated BP records within each pregnancy . In each trimester , mean systolic BP ( SBP ) and diastolic BP ( DBP ) values were positively associated with maternal pre-gestational BMI . This association persisted after adjustment for maternal age , parity , smoking , education , marital status and physical activity . Overweight women ( 25 - 29 kg/m(2 ) ) had first- , second- and third-trimester mean SBPs that were 8.1 , 7.7 and 8.2 mmHg , respectively , higher than values observed in lean women ( < 20 kg/m(2 ) ) . Mean DBP values were 4.5 , 5.4 and 5.6 mmHg higher for each successive trimester in overweight vs. lean women . Obese ( > 30 kg/m(2 ) ) women consistently had the highest mean SBP and DBP values . Trimester-specific mean SBP values were 10.7 - 12.0 mmHg higher among obese women vs. lean women . Corresponding trimester-specific mean DBP values were 6.9 - 7.4 mmHg higher in obese vs. lean women . Similar patterns were observed when trimester-specific average mean arterial pressures were evaluated . Elevated pregnancy BPs associated with maternal pre-gestational BMI are consistent with a large body of literature that documents increased pre-eclampsia risk among overweight and obese women Objective : To establish the profiles of 24-h non-invasive ambulatory blood pressure measurement ( ABPM ) during the trimesters of pregnancy and the puerperium in normotensive healthy primigravidae Design : A prospect i ve study in which 24-h ABPM was performed on five occasions in each subject : in the first trimester between 9 and 16 weeks ' gestation ; in the second trimester between 18 and 24 weeks ; in the third trimester between 26 and 32 weeks and between 33 and 40 weeks ; and finally at 6 weeks post partum Method : One hundred and six Caucasian primigravid women who were normotensive at their first booking visit were recruited consecutively from the antenatal clinic and had 24-h ABPM performed with the SpaceLabs 90207 ambulatory system Results : Of the 106 women recruited , 98 completed 24-h ABPM on four of the five measurement occasions . Four women delivered prematurely before 33 weeks ' gestation , thereby missing one ABPM measurement . Changes during pregnancy and the puerperium were assessed against the ABPM performed in the first trimester . There was no difference for daytime or night-time systolic blood pressure between 9 and 33 weeks , but it rose significantly from 33 to 40 weeks . At 6 weeks post partum , systolic blood pressure was not significantly different from the daytime pressure in the first-trimester ABPM but was raised significantly at night . Diastolic blood pressure decreased significantly between 18 and 24 weeks for both daytime and night-time . From 33 to 40 weeks it increased in parallel with systolic blood pressure , and at 6 weeks post partum it was raised significantly compared with first-trimester values for daytime and night-time . The nocturnal fall in blood pressure was preserved throughout pregnancy with a significant difference between daytime and night-time measurements present on all measurement occasions for systolic , diastolic and mean blood pressures and heart rate . There were significant differences between daytime ABPM and clinic blood pressure for both systolic and diastolic blood pressure up to 33 weeks . From 33 weeks until 6 weeks post partum there was no significant difference between daytime ambulatory and clinic blood pressures Conclusion : This study provides reference values for ABPM in healthy primigravidae with generally uncomplicated Objective : To study longitudinally changes in blood pressure ( BP ) and heart rate ( HR ) during healthy pregnancies and to evaluate the influence of parity , pregestational overweight , and excessive weight gain . Methods : A prospect i ve longitudinal cohort study of 57 healthy white women with singleton pregnancies . BP and HR were measured repeatedly at gestational age 14–16 weeks , 22–24 weeks , 30–32 weeks , 36 weeks , and 6 months postpartum using both an oscillometric measurement device ( Dinamap ) and finger arterial pressure ( Finometer PRO ) . Results : SBP , DBP , and mean arterial pressure ( MAP ) reached a statistically significant trough at gestational age 22–24 weeks using both measurement devices . When compared with the nonpregnant measurement , SBP at gestational age 22–24 weeks was 6.2 mmHg [ 95 % confidence interval ( 95 % CI ) 1.3–11.2 ] lower measured by Finometer and 7.2 mmHg ( 95 % CI 4.2–10.1 ) lower measured by Dinamap . DBP and MAP were 8.9 mmHg ( 95 % CI 4.6–13.2 ) and 9.8 mmHg ( 95 % CI 5.3–14.2 ) lower measured by Finometer . Measured by Dinamap , DBP and MAP were 4.5 mmHg ( 95 % CI 1.7–7.3 ) and 5.4 mmHg ( 95 % CI 2.8–7.9 ) lower at gestational age 22–24 weeks when compared with the nonpregnant state . SBP was significantly higher in women with pregestational BMI at least 25 kg/m2 with both measurement devices ( both P < 0.05 ) . There were no differences in SBP , DBP , or MAP depending on parity or excessive weight gain . Conclusion : BP measured repeatedly by two different noninvasive devices during pregnancy and postpartum showed a statistically significant drop in mid-pregnancy , followed by a progressive increase until term Background Pregnancy associated cardiovascular pathologies have a significant impact on outcome for mother and child . Bioimpedance cardiography may provide additional outcome -relevant information early in pregnancy and may also be used as a predictive instrument for pregnancy-associated diseases . Methods We performed a prospect i ve longitudinal cohort trial in an outpatient setting and included 242 pregnant women . Cardiac output and concomitant hemodynamic data were recorded from 11th–13th week of gestation every 5th week as well as at two occasions post partum employing bioimpedance cardiography . Results Cardiac output increased during pregnancy and peaked early in the third trimester . A higher heart rate and a decreased systemic vascular resistance were accountable for the observed changes . Women who had a pregnancy-associated disease during a previous pregnancy or developed hypertension or preeclampsia had a significantly increased cardiac output early in pregnancy . Furthermore , an effect of cardiac output on birthweight was found in healthy pregnancies and could be confirmed with multiple linear regression analysis . Conclusions Cardiovascular adaptation during pregnancy is characterized by distinct pattern described herein . These may be altered in women at risk for preeclampsia or reduced birthweigth . The assessment of cardiac parameters by bioimpedance cardiography could be performed at low costs without additional risks STUDY QUESTION Are there differences in preconception cardiovascular function between women who have a viable pregnancy and those who have a first trimester miscarriage ? SUMMARY ANSWER Preconception cardiovascular function of central haemodynamics and arterial function are similar between women who have a viable pregnancy and those who have a first trimester miscarriage . WHAT IS KNOWN ALREADY Miscarriages have been associated with increased long-term cardiovascular disease risk , and arterial and cardiovascular dysfunction has been hypothesised as the common link . It is not known if these risks are present prior to pregnancy or are a reflection of poor arterial and haemodynamic adaptation to pregnancy . STUDY DESIGN , SIZE , DURATION This prospect i ve longitudinal preconception cohort study was conducted over 18 months . In total , 367 participants were recruited pre-pregnancy , from which 197 pregnancies were recorded ; 39 of these pregnancies ended in first trimester miscarriage . Complete longitudinal data were available for 172 pregnancies ( 140 viable pregnancies , 32 first trimester miscarriages ) from pre-pregnancy to 6 weeks gestation . PARTICIPANTS / MATERIAL S , SETTING , METHODS This was a single site study based at a maternity hospital in London . Healthy women were recruited prior to natural conception and followed up once they became pregnant . All underwent haemodynamic [ cardiac output ( CO ) , peripheral vascular resistance ( PVR ) ] and arterial function [ aortic augmentation index ( AIx ) and pulse wave velocity ( PWV ) ] testing prior to pregnancy and at 6 weeks gestation , using non-invasive devices ( gas re-breathing method , Innocor ® and an occilometric device , Vicorder ® ) . Cross-sectional measurements at pre-pregnancy and 6 weeks gestation and a longitudinal analysis of changes were compared between women who had a subsequent viable pregnancy , and those who had a subsequent first trimester miscarriage . MAIN RESULTS AND THE ROLE OF CHANCE There were no differences between women destined to have a healthy ongoing pregnancy compared to those who miscarried , in terms of baseline cardiovascular function , assessed by CO , PVR , PWV or AIx . Similarly , between the groups , there were no differences in pregnancy adaptation with similar trends in cardiovascular function changes from pre-pregnancy to 6 weeks gestation . LIMITATIONS , REASONS FOR CAUTION Whilst this is the first study to investigate preconception and early pregnancy haemodynamic and arterial function in relation to viability , the relatively modest number of miscarriages may not be sufficient to show subtle differences in haemodynamic changes if these were present . WIDER IMPLICATION S OF THE FINDINGS This study suggests that pre-pregnancy haemodynamic and arterial function is unlikely to be the causal link between miscarriages and future cardiovascular disease . Our findings suggests that factors other than the presence of a viable embryo drive cardiovascular changes in early pregnancy . This study raises new questions about miscarriages as an independent risk event which predisposes women to increased cardiovascular risk later in life . STUDY FUNDING /COMPETING INTEREST(S ) The investigators are funded by NIHR Imperial BRC , NIHR Cambridge BRC , Action Medical Research , Imperial College Healthcare Charity and Tommy 's Charity . We acknowledge the loan of ultrasound equipment from Samsung Medison ( South Korea)/MIS Ltd and provision of fertility monitors from SPD Development Company Ltd ( Bedford , UK ) . There are no competing interests . C.C.L. is supported by the UK National Institute for Health Research Biomedical Research Centre based at Imperial College Healthcare National Health Service Trust and Imperial College London . TRIAL REGISTRATION NUMBER Objective : To extend findings that African American women report greater stress during pregnancy , have higher blood pressure ( BP ) , and are twice as likely to have low birthweight infants relative to white women . This study examines a ) racial differences in associations between stress and BP during pregnancy , and b ) the combined effects of stress and BP on infant birthweight in a sample of 170 African American and white women . Methods : A prospect i ve , longitudinal study of pregnant women was conducted in which measures of BP , stress , and other relevant variables were collected . Multiple measures of systolic and diastolic BP were taken at each of three points during pregnancy ( 18–20 , 24–26 , and 30–32 weeks gestation ) . Results : Both systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) were positively associated with stress in pregnant African American women and not in pregnant white women . In analyses of birthweight , there were no main effects of BP or stress . However , a significant interaction demonstrated that , when stress was high , DBP was negatively associated with birthweight and a combination of high stress and high DBP predicted the lowest birthweight in the sample . Furthermore , African American women were twice as likely as white women to have a combination of high stress and high DBP . Conclusions : Racial differences in relationships between stress and BP , and the interactive effect of stress and DBP on birthweight together suggest that a high stress-high BP profile may pose a risk for lower birthweight among African American women , in particular , and possibly for all pregnant women . BP = blood pressure ; DBP = diastolic blood pressure ; SBP = systolic blood pressure ; BMI = body mass index ; Ms = means Abstract This article evaluates the association of hepatic , renal , and inflammatory biomarkers with changes in systolic ( SBP ) and diastolic ( DBP ) blood pressure ( BP ) during healthy pregnancies . A prospect i ve cohort study with 225 healthy pregnant women was conducted in Rio de Janeiro , Brazil . SBP and DBP were evaluated throughout pregnancy ( 5th–13th , 20th–26th , and 30th–36th gestational weeks ) and were the outcomes . The following biomarkers were measured at the first trimester and analyzed according to tertiles of the sample distribution and were considered the main independent predictors : alkaline phosphatase ( ALP ) , alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , uric acid ( UA ) , creatinine ( Cr ) , and C-reactive protein ( CRP ) concentrations . The statistical analysis included 3 stages of modeling with the longitudinal linear mixed-effects procedures : Model 1 was adjusted for gestational age and quadratic gestational age ; Model 2 included interactions between the biomarkers and gestational age ; and Model 3 was adjusted for self-reported skin color , education , parity , early-pregnancy body mass index ( BMI ) ( under/normal < 25 ; overweight/obese ≥25 kg/m2 ) , smoking habit , and leisure-time physical activity . Additional models were performed for CRP and UA with the inclusion of interaction terms between the biomarkers and BMI .Women classified in the third tertile of the ALP ( ≥61.1 U/L ; & bgr;SBP = 3.474 ; 95 % confidence interval [ CI ] : 0.955–5.992 ; & bgr;DBP = 3.291 ; 95 % CI : 1.098–5.485 ) , ALT ( ≥14.3 U/L ; & bgr;SBP = 2.232 ; 95 % CI : 0.221–4.242 ; & bgr;DBP = 2.355 ; 95 % CI : 0.721–3.989 ) , and Cr values ( ≥48.6 & mgr;mol/L ; & bgr;DBP = 1.927 ; 95 % CI : 0.347–3.508 ) presented higher BP levels during pregnancy compared to those in the first and second tertiles . Women in the highest tertile of the ALP concentration distribution presented a lower rate of change in SBP and DBP during pregnancy ( interaction term with gestational age & bgr;SBP = −0.004 ; 95 % CI : −0.007 to −0.001 ; P = 0.02 ; & bgr;DBP = −0.003 ; 95 % CI : −0.006 to −0.001 ; P = 0.01 ) . Higher UA concentrations were associated with higher SBP levels only in overweight/obese women ( & bgr ; = 3.878 ; 95 % CI : 0.687–7.068 ) , whereas higher CRP concentrations ( ≥2.6 mg/L ) were associated with higher DBP in under/normal weight women ( & bgr ; = 2.252 ; 95 % CI : 0.267–4.236).ALP , ALT , and Cr concentrations were positively associated with BP levels , whereas ALP was associated with a lower rate of change in BP . The associations of UA and CRP with BP differ according to the early-pregnancy BMI BACKGROUND Maternal exposure to ambient air pollution has been associated with adverse birth outcomes such as preterm delivery . However , only one study to date has linked air pollution to blood pressure changes during pregnancy , a period of dramatic cardiovascular function changes . OBJECTIVES We examined whether maternal exposures to criteria air pollutants , including particles of less than 10 μm ( PM(10 ) ) or 2.5 μm diameter ( PM(2.5 ) ) , carbon monoxide ( CO ) , nitrogen dioxide ( NO(2 ) ) , sulfur dioxide ( SO(2 ) ) , and ozone ( O(3 ) ) , in each trimester of pregnancy are associated with magnitude of rise of blood pressure between the first 20 weeks of gestation and late pregnancy in a prospect ively followed cohort of 1684 pregnant women in Allegheny County , PA . METHODS Air pollution measures for maternal ZIP code areas were derived using Kriging interpolation . Using logistic regression analysis , we evaluated the associations between air pollution exposures and blood pressure changes between the first 20 weeks of gestation and late pregnancy . RESULTS First trimester PM(10 ) and ozone exposures were associated with blood pressure changes between the first 20 weeks of gestation and late pregnancy , most strongly in non-smokers . Per interquartile increases in first trimester PM(10 ) and O(3 ) concentrations were associated with mean increases in systolic blood pressure of 1.88 mm Hg ( 95 % CI=0.84 to 2.93 ) and 1.84 ( 95 % CI=1.05 to 4.63 ) , respectively , and in diastolic blood pressure of 0.63 mm Hg ( 95 % CI=-0.50 to 1.76 ) and 1.13 ( 95 % CI=-0.46 to 2.71 ) in non-smokers . CONCLUSIONS Our novel finding suggests that first trimester PM(10 ) and O(3 ) air pollution exposures increase blood pressure in the later stages of pregnancy . These changes may play a role in mediating the relationships between air pollution and adverse birth outcomes Objective Although a large variety of automated blood pressure devices are available , only some have been vali date d for use in clinical practice . The British Hypertension Society ( BHS ) recommends separate validation of automated devices in special subgroups , e.g. the elderly and pregnant women . The aim of this study was to compare the FinometerTM ( FM ) and the earlier vali date d SpaceLabs 90207TM ( SL ) with st and ard auscultatory blood pressure measurements in normal , pre-eclamptic and hypertensive pregnancy , following the guidelines of the BHS and the Association for the Advancement of Medical Instrumentation ( AAMI ) . Methods The total study group consisted of 123 pregnant women , of whom were 54 normotensive , 31 pre-eclamptic and 38 hypertensive . Automated readings with the FM and SL were compared with auscultatory blood pressure measurements . Bl and –Altman plots , BHS grade s , mean pressure differences and 95 % limits of agreement were used for analysis . Results Bl and –Altman plots showed a wide scatter of the pressure differences between auscultatory and automated measurements . FM achieved BHS grade s C/D , C/B , D/D and D/D in the total , normotensive , pre-eclamptic and hypertensive group , respectively . The AAMI criteria were only met for diastolic blood pressure in the normotensive group . For SL almost identical BHS grade s and 95 % limits of agreement as compared to our earlier study were found . Conclusions The accuracy and precision of the FinometerTM are not sufficient for determination of absolute blood pressure levels in individual pregnant women . Our present findings on the SpaceLabs 90207TM reconfirm our earlier results Background Current dogma states that there is a mid-trimester fall in blood pressure ( BP ) in uncomplicated pregnancy . In the early stages of a longitudinal study of microcirculatory changes in pregnancy , we noted an absence of this mid-trimester fall . Method We prospect ively studied this phenomenon in all our subsequent recruits . From a total of 326 women , 255 primigravid white women normotensive at booking and after delivery were studied . Serial BP measurements were taken under controlled conditions through to 38 weeks gestation . BP measurements by midwives were extracted from the case notes of 51 women within this cohort and analysed to vali date the results . SBP progressively increased from the first trimester through to 38 weeks gestation . Results The increase from baseline at 13 weeks was significant when compared with measurements at 22 weeks [ mean difference : 2.8 mmHg ; 95 % ( confidence interval ) CI 1.9–3.7 ] , 28 weeks ( mean difference : 5.0 mmHg ; 95 % CI 3.5–6.5 ) and 36 weeks ( mean difference : 7.7 mmHg ; 95 % CI 6.2–9.1 ) . DBP showed a nonsignificant dip at 22 weeks ( mean difference : −0.12 mmHg ; 95 % CI −0.92 to 0.68 ) , a nonsignificant increase at 28 weeks ( mean difference : 2.0 mmHg ; 95 % CI 0.80–3.2 ) and a significant increase at 36 weeks ( mean difference : 6.0 ; 95 % CI 4.6–7.3 ) . In the validation cohort , the SBP ( P = 0.0001 ) and DBP showed an increasing trend ( P = 0.0001 ) . Conclusion BP measured under controlled conditions showed a progressive rise in pregnancy , with no significant mid-trimester drop . The findings were replicated in the routine antenatal clinic measurements This paper examines the relationship between smoking levels and blood pressure patterns of normotensive pregnant women in a prospect i ve cohort of 2193 primiparous and 3176 multiparous , normotensive , Caucasian women selected from the Child Health and Development Studies in Oakl and , California , 1959 - 67 . Regression lines were fitted to each woman 's blood pressure ; mean intercept and slope estimates of the individual regressions were used to create summary profile lines for each smoking dose . Multivariable regression analysis controlled for maternal age , number of visits to the doctor after 20 weeks ' gestation , body mass index and maternal education level . Overall , smokers had lower average diastolic blood pressure ( smokers vs. nonsmokers adjusted mean : primiparas , 66.1 vs. 67.2 mmHg ; and multiparas , 64.0 vs. 64.7 mmHg ) but higher systolic blood pressure ( smokers vs. nonsmokers adjusted mean : primiparas , 117.0 vs. 116.0 ; and multiparas , 112.5 vs. 110.0 ) than nonsmokers among primiparous and multiparous pregnant women after adjusting for potential confounders . However , these differences are small and there was no clear dose-response relationship between smoking level and blood pressure Objective Smoking during pregnancy is a risk factor for various adverse birth outcomes but lowers the risk of preeclampsia . Cardiovascular adaptations might underlie these associations . We examined the associations of smoking in different trimesters of pregnancy with repeatedly measured blood pressure and the risks of preeclampsia and pregnancy-induced hypertension in a low-risk population -based cohort of 7106 pregnant women . Methods This study was embedded in a population -based prospect i ve cohort study from early pregnancy onwards . Smoking and systolic and diastolic blood pressures were assessed by question naires and physical examinations in each trimester of pregnancy . Information about preeclampsia and pregnancy-induced hypertension was obtained from medical records . Results Compared to nonsmoking women , both first-trimester-only and continued smoking were associated with a steeper increase for systolic blood pressure and a lowest mid-pregnancy level and steeper increase thereafter for diastolic blood pressure throughout pregnancy . We did not find any significant associations in risk of preeclampsia for first-trimester-only smoking ( odds ratio of 1.28 , 95 % confidence interval 0.74 , 2.21 ) and continued smoking ( odds ratio of 0.83 , 95 % confidence interval 0.50 , 1.36 ) , respectively . Conclusions Our results suggest that both first-trimester-only and continued smoking are associated with persistent maternal cardiovascular adaptations during pregnancy . Strategies for prevention of smoking during pregnancy should be focused on the preconception period . The effects of early and late-pregnancy smoking on the risk of preeclampsia should be further explored . Our results should be carefully interpreted to the general population of pregnant women BACKGROUND : It is commonly taught that patients with multiple gestation pregnancy are prone to more severe hypotension during spinal and epidural anesthesia compared to those with singleton pregnancy . However , few quantitative data are available to support this cl aim . In this study , we prospect ively compared vasopressor requirement and hemodynamic changes in patients with multiple gestation versus singleton pregnancy during spinal anesthesia for elective cesarean delivery . METHODS : Forty parturients with multiple gestation and 60 singleton controls who had identical anesthetic management during spinal anesthesia for elective cesarean delivery were enrolled . After IV prehydration , patients received intrathecal bupivacaine-fentanyl and were tilted to the left . A metaraminol infusion was titrated with the target of maintaining systolic blood pressure at 90%–100 % of baseline . Vasopressor dose , minimum and maximum values for systolic blood pressure and the incidences of hypotension , hypertension , and nausea/vomiting were compared . RESULTS : All outcome variables were similar between groups . The total dose of metaraminol required until uterine incision was similar in multiple gestation pregnancy ( median 2.9 [ interquartile range 2.0–3.7 ] mg ) when compared with singleton pregnancy ( median 3.1 [ interquartile range 2.3–3.9 ] mg , P = 0.25 ; median difference 0.30 mg , 95 % confidence interval of difference −0.20 to 0.90 mg ) . Neonatal outcome was similar between groups . CONCLUSION : Patients with multiple gestation pregnancy do not exhibit greater hemodynamic instability during spinal anesthesia for cesarean delivery compared to those with singleton pregnancy Objective : Our objective was to investigate the extent of changes in maternal cardiovascular function , lipids and renal function during normal pregnancy from preconception to postpartum period . Methods : In this prospect i ve study of 54 normal pregnancies , detailed hemodynamics were performed preconception , at 6 , 23 and 33 weeks during pregnancy and 16 weeks postpartum . Results : Although the greatest reduction of blood pressures ( BPs ) and augmentation index occurred in early pregnancy ( & Dgr;brachial systolic : 4 ± 7 mmHg , & Dgr ; central systolic : 7 ± 7 mmHg ; P < 0.001 ) , the peripheral vascular resistance reached a nadir ( & Dgr ; : 222 ± 215 dynes.s−1.cm−5 ; P < 0.001 ) by the second trimester . The greatest increase in cardiac output occurred by the second trimester ( & Dgr ; : 0.6 ± 1 l/min , P < 0.001 ) , whereas the heart rate increased maximally by the third trimester ( & Dgr ; : 13 ± 11 bpm ; P = 0.001 ) . The unadjusted aortic pulse wave velocity decreased in the second trimester ( P < 0.001 ) , however , when adjusted for mean arterial pressure this was not significant ( P = 0.06 ) . BPs were lower ( & Dgr ; brachial systolic : 5 ± 8 mmHg ; P < 0.001 ) and augmentation index higher ( & Dgr ; : 2.5 ± 7 % ; P = 0.01 ) postpartum than preconception . The cholesterol : high-density lipoprotein ratio , serum low density lipoprotein and serum creatinine all fell ( P < 0.001 ) in the first trimester . Conclusion : We have shown that normal pregnancy , irrespective of parity , is associated with significant changes commencing very early in pregnancy , continuing throughout pregnancy , and some of these changes persisted postpartum . Therefore , first trimester or postpartum baselines will underestimate the true extent of pregnancy-related changes . Prospect i ve studies of cardiovascular function from preconception to postpartum will provide more reliable estimates of the influence of cardiovascular maladaptation during pregnancy complications and their effect on longer term cardiovascular function A changed pressor response to some cardiovascular reflex tests and an increase in midtrimester blood pressure has been reported to precede the appearance of hypertension in pregnancy-induced hypertensive disorders ( PIH ) . In order to compare the value of midtrimester blood pressure with the cardiovascular reflex tests , in predicting the risk of PIH , the Valsalva manoeuvre , the orthostatic test , the deep breathing test and the isometric h and grip test were performed prospect ively in 94 women studied once at 21 - 29 weeks of pregnancy . Eight subjects developed PIH 3 - 12 weeks after the testing . The resting blood pressure in midpregnancy was related to PIH later in pregnancy . The most powerful measures were the supine diastolic resting blood pressure ( odds ratio , 1.24 ; 95 % confidence limits , 1.08 - 1.43 ) and the mean arterial pressure ( odds ratio , 1.25 ; 95 % confidence limits , 1.09 - 1.44 ) . Signs of autonomic dysfunction were found in 37 % of the patients developing PIH and in 8 % of the healthy remaining subjects ( P = 0.04 ) . The results show that the pre clinical stage of PIH is associated with some changes in the neural hemodynamic control . However , cardiovascular reflex tests do not add much information on the risk of PIH compared with measuring of the resting blood pressure during mid-pregnancy OBJECTIVE To investigate the maternal hemodynamic changes that occurs during pregnancy . To find out the difference that lie in healthy pregnancy and women with gestational hypertension . To introduce a method that is applied to shift high-risk women of gestational hypertension in pregnancy women . METHOD Serial hemodynamic investigations ( total 8 times ) were performed throughout pregnancy period by radioulnar pulse wave electrical monitoring in 182 women ( 130 with healthy pregnancies , 52 with gestational hypertension ) . Analysis of variance with repeated measurements was used to evaluate the course of a number of hemodynamic indices . To identify the correlation between these changes and gestational hypertension by using above method . RESULTS A significant difference in mean arterial pressure ( MAP ) , cardiac output ( CO ) , cardiac index ( CI ) , total Peripheral Resistance ( TPR ) and heart rat ( HR ) was observed different between normal pregnancy and women with gestational hypertension . The changes of parameters in normal woman and gestational hypertension were recorded and the mechanism of gestational hypertension was heterogenous . CONCLUSION These results provide sensitive parameters for use in early risk assessment and as a guide to preventive intervention during pregnancy |
743 | 27,765,575 | CONCLUSION Exercise interventions can improve certain falls-related outcomes among older adults with DM .
Among older adults , where DM burden is increasing , exercise interventions may provide promising approaches to assist the improvement of falls-related outcomes | INTRODUCTION Falls as a complication of diabetes mellitus ( DM ) can have a major impact on the health of older adults .
Previous review s have demonstrated that certain exercise interventions are effective at reducing falls in older people ; however , no studies have quantified the effectiveness of exercise interventions on falls-related outcomes among older adults with DM . | This study evaluated the effects of a 6-month combined aerobic and resistance training program on the body composition , glycemic control , lipid profile , and functional capacity of older patients with a long history of type 2 diabetes . 25 subjects ( 65.9 ± 4 . 2 yrs ; M/F : 13/12 ) with a long history of type 2 diabetes ( 16.7 ± 6.7 yrs ) were r and omly allocated into either the exercise or control groups . The exercise group trained three sessions a week . Each session consisted of a warm-up period , 30 minutes of moderate aerobic exercise , 10 minutes of resistance training with five leg muscle exercises ( two sets of 10 - 12 repetitions at 50 - 70 % of 1RM for each activity ) , and a cool-down period . The variables of body composition , glycemic control , lipid profile , and functional capacity were measured before and after the study period . Exercise training decreased waist-hip ratio and body fat of the trained subjects . Concentrations of fasting and 2-hour post-glucose challenge plasma glucose and serum insulin , and glycosylated hemoglobin decreased significantly in the exercise group . Exercise training improved the lipid profile and also increased the leg muscle strength and 6-minute walking distance of the trained subjects . The control group , however , increased their body fat and fasting plasma glucose , while other variables were not changed during the study period . The current results demonstrate that elderly patients with a long history of type 2 diabetes can benefit from the 6-month combined aerobic and resistance training program . Key pointsExercise training is effective for elderly patients with long-term type 2 diabetesExercise prescription for elderly patients with type 2 diabetes should contain both aerobic and resistance activities PURPOSE The aim of this study was to determine the effects of Tai Chi exercise on glucose control , neuropathy scores , balance , and quality of life in patients with type 2 diabetes and neuropathy . METHODS A pretest-posttest design with a nonequivalent control group was utilized to recruit 59 diabetic patients with neuropathy from an outpatient clinic of a university hospital . A st and ardized Tai Chi for diabetes program was provided , which comprised 1 hour of Tai Chi per session , twice a week for 12 weeks . Outcome variables were fasting blood glucose and glycosylated hemoglobin for glucose control , the Semmes-Weinstein 10-g monofilament examination scores and total symptom scores for neuropathy , single leg stance for balance , and the Korean version of the SF-36v2 for quality of life . Thirty-nine patients completed the posttest measures after the 12-week Tai Chi intervention , giving a 34 % dropout rate . RESULTS The mean age of the participants was 64 years , and they had been diagnosed with type 2 diabetes for more than 12 years . The status was significantly better for the participants in the Tai Chi group ( n=20 ) than for their control ( i.e. , nonintervention ) counterparts ( n=19 ) in terms of total symptom scores , glucose control , balance , and quality of life . CONCLUSION Tai Chi improved glucose control , balance , neuropathic symptoms , and some dimensions of quality of life in diabetic patients with neuropathy . Further studies with larger sample s and long-term follow-up are needed to confirm the effects of Tai Chi on the management of diabetic neuropathy , which may have an impact on fall prevention in this population OBJECTIVE This study assessed the effects of balance/strength training on falls risk and posture in older individuals with type 2 diabetes . RESEARCH DESIGN AND METHODS Sixteen individuals with type 2 diabetes and 21 age-matched control subjects ( aged 50–75 years ) participated . Postural stability and falls risk was assessed before and after a 6-week exercise program . RESULTS Diabetic individuals had significantly higher falls risk score compared with control subjects . The diabetic group also exhibited evidence of mild-to-moderate neuropathy , slower reaction times , and increased postural sway . Following exercise , the diabetic group showed significant improvements in leg strength , faster reaction times , decreased sway , and , consequently , reduced falls risk . CONCLUSIONS Older individuals with diabetes had impaired balance , slower reactions , and consequently a higher falls risk than age-matched control subjects . However , all these variables improved after resistance/balance training . Together these results demonstrate that structured exercise has wide-spread positive effects on physiological function for older individuals with type 2 diabetes BACKGROUND Strength training has been shown to be beneficial in older adults . However , very little data exist on the effects of strength training in older diabetics . METHODS 31 community-dwelling older adults with diabetes ( mean age = 66.1 years ) were r and omly assigned to either an exercise ( EX ) or control ( CO ) group . The EX group trained the plantar flexors , knee extensors , knee flexors , hip extensors , and hip flexors muscle groups at 50 % , 60 % , and 70 % of 1-repetition maximum , 2.6 days a week , for 24 months . Mobility tests included the timed up and go , 50-foot walk , and walking up and down 8 stairs . Strength and mobility for both groups were evaluated at 6-month intervals . RESULTS There was a group and time effect as the EX group increased 31.4 % ( p < .001 ) in strength for all muscle groups after the first 6 months of training , and the strength gains were retained for the duration of the training intervention . There was also a group and time effect for mobility as performance increased 8.6 % and 9.8 % ( p = .032 and p = 0.031 ) for the first 6 and 12 months , respectively , but decreased to 4.6 % above baseline at the end of the intervention . There were essentially no changes from baseline strength or mobility values for the CO group . CONCLUSION In conclusion , these data suggest that a moderate-intensity resistive-training program can improve mobility and strength for the duration of a 24-month intervention in older adults with diabetes , thus potentially reducing the rate of mobility loss during aging Background Interventions for preventing falls in older people often involve several components , multidisciplinary teams , and implementation in a variety of setting s. We have developed a classification system ( taxonomy ) to describe interventions used to prevent falls in older people , with the aim of improving the design and reporting of clinical trials of fall-prevention interventions , and synthesis of evidence from these trials . Methods Thirty three international experts in falls prevention and health services research participated in a series of meetings to develop consensus . Robust techniques were used including literature review s , expert presentations , and structured consensus workshops moderated by experienced facilitators . The taxonomy was refined using an international test panel of five health care practitioners . We assessed the chance corrected agreement of the final version by comparing taxonomy completion for 10 r and omly selected published papers describing a variety of fall-prevention interventions . Results The taxonomy consists of four domains , summarized as the " Approach " , " Base " , " Components " and " Descriptors " of an intervention . Sub-domains include ; where participants are identified ; the theoretical approach of the intervention ; clinical targeting criteria ; details on assessment s ; descriptions of the nature and intensity of interventions . Chance corrected agreement of the final version of the taxonomy was good to excellent for all items . Further independent evaluation of the taxonomy is required . Conclusions The taxonomy is a useful instrument for characterizing a broad range of interventions used in falls prevention . Investigators are encouraged to use the taxonomy to report their interventions Background . Peak oxygen uptake ( VO2peak ) and muscle function are more decreased in patients with a combination of chronic heart failure ( CHF ) and type 2 diabetes mellitus ( 2DM ) compared to patients with only one of the conditions . Further , patients with 2DM have peripheral complications that hamper many types of conventional exercises . Aim . To evaluate the efficacy and applicability of eight-week aquatic exercise in patients with the combination of CHF and 2DM . Methods . Twenty patients ( four women ) with both CHF and 2DM ( age 67.4 ± 7.1 , NYHA II-III ) were r and omly assigned to either aquatic exercise or a control group . The patients exercised for 45 minutes 3 times/week in 33–34 ° C , swimming pool . Results . The training programme was well tolerated . Work rate ( + 11.7 ± 6.6 versus −6.4 ± 8.1 watt , P < 0.001 ) and VO2peak ( + 2.1 ± 0.8 versus −0.9 ± 1.4 mL·kg−1·min−1 , P < 0.001 ) and walking capacity ( P = 0.01 ) increased significantly in the training group . Muscle function was also significantly improved and Hba1c decreased significantly ( P < 0.01 ) during training , while fasting glucose , insulin , c-peptide , and lipids were unchanged . Training also increased vitality measured by SF-36 significantly ( P = 0.05 ) . Conclusion . Aquatic exercise could be used to improve exercise capacity and muscle function in patients with the combination of CHF and 2DM Hispanics are at increased risk of morbidity and mortality due to their high prevalence of diabetes and poor glycemic control . Strength training is the most effective lifestyle intervention to increase muscle mass but limited data is available in older adults with diabetes . We determined the influence of strength training on muscle quality ( strength per unit of muscle mass ) , skeletal muscle fiber hypertrophy , and metabolic control including insulin resistance ( Homeostasis Model Assessment –HOMA-IR ) , C-Reactive Protein ( CRP ) , adiponectin and Free Fatty Acid ( FFA ) levels in Hispanic older adults . Sixty-two community-dwelling Hispanics ( > 55 y ) with type 2 diabetes were r and omized to 16 weeks of strength training plus st and ard care ( ST group ) or st and ard care alone ( CON group ) . Skeletal muscle biopsies and biochemical measures were taken at baseline and 16 weeks . The ST group show improved muscle quality ( mean±SE : 28±3 ) vs CON ( -4±2 , p<0.001 ) and increased type I ( 860±252µm2 ) and type II fiber cross-sectional area ( 720±285µm2 ) compared to CON ( type I : -164±290µm2 , p=0.04 ; and type II : -130±336µm2 , p=0.04 ) . This was accompanied by reduced insulin resistance [ ST : median ( interquartile range ) -0.7(3.6 ) vs CON : 0.8(3.8 ) , p=0.05 ] ; FFA ( ST : -84±30µmol/L vs CON : 149±48µmol/L , p=0.02 ) ; and CRP [ ST : -1.3(2.9)mg/L vs CON : 0.4(2.3)mg/L , p=0.05 ] . Serum adiponectin increased with ST [ 1.0(1.8)µg/mL ] compared to CON [ -1.2(2.2)µg/mL , p<0.001 ] . Strength training improved muscle quality and whole-body insulin sensitivity . Decreased inflammation and increased adiponectin levels were related with improved metabolic control . Further studies are needed to underst and the mechanisms associated with these findings . However , these data show that strength training is an exercise modality to consider as an adjunct of st and ard of care in high risk population s with type 2 diabetes The prevention of injury associated with falls in older people is a public health target in many countries around the world . Although there is good evidence that interventions such as multifactorial fall prevention and individually prescribed exercise are effective in reducing falls , the effect on serious injury rates is unclear . Historically , trials have not been adequately powered to detect injury endpoints , and variations in case definition across trials have hindered meta- analysis . It is possible that fall-prevention strategies have limited effect on falls that result in injuries or are ineffective in population s who are at a higher risk of injury . Further research is required to determine whether fall-prevention interventions can reduce serious injuries . Prevention of Falls Network Europe ( ProFaNE ) is a collaborative project to reduce the burden of fall injury in older people through excellence in research and promotion of best practice ( www.profane.eu.org ) . The European Commission funds the network , which links clinicians , members of the public , and research ers worldwide . The aims are to identify major gaps in knowledge in fall injury prevention and to facilitate the collaboration necessary for large-scale clinical research activity , including clinical trials , comparative research , and prospect i ve meta- analysis . Work is being undertaken in a 4-year program . As a first step , the development of a common set of outcome definitions and measures for future trials or meta- analysis was considered OBJECTIVE To examine the effects of an 8-week home-based resistance exercise program on balance , power , and mobility in adults with multiple sclerosis . DESIGN Experimental group design . SETTING General community . PARTICIPANTS Twenty-nine women ( age , 50.3+/-8.5 y ) and 8 men ( age , 51.1+/-7.1 y ) were stratified by disability level and age and were r and omized into exercise ( n=19 ) and control ( n=17 ) groups . INTERVENTION The exercise group had lower-extremity resistance training 3 times a week . The control group maintained current level of physical activity . Main outcome measures Primary outcome measures included balance , as measured by anteroposterior sway , mediolateral sway , and sway velocity using the AccuSway(PLUS ) force platform ; mobility as assessed with the Up and Go test ; and leg power as assessed with the Leg Extensor Power Rig . RESULTS Leg extensor power improved significantly in the exercise group ( pretest , 3.19+/-1.36 W/kg ; posttest , 3.95+/-1.23 W/kg ; P=.004 ) , although measures of balance and mobility did not change . CONCLUSIONS The home-based resistance program was well tolerated by participants and offered a practical means to improve leg extensor power in a short period of time Background : Individuals with diabetic peripheral neuropathy ( DPN ) have deficits in sensory and motor skills leading to inadequate proprioceptive feedback , impaired postural balance and higher fall risk . Objective : This study investigated the effect of sensor-based interactive balance training on postural stability and daily physical activity in older adults with diabetes . Methods : Thirty-nine older adults with DPN were enrolled ( age 63.7 ± 8.2 years , BMI 30.6 ± 6 , 54 % females ) and r and omized to either an intervention ( IG ) or a control ( CG ) group . The IG received sensor-based interactive exercise training tailored for people with diabetes ( twice a week for 4 weeks ) . The exercises focused on shifting weight and crossing virtual obstacles . Body-worn sensors were implemented to acquire kinematic data and provide real-time joint visual feedback during the training . Outcome measurements included changes in center of mass ( CoM ) sway , ankle and hip joint sway measured during a balance test while the eyes were open and closed at baseline and after the intervention . Daily physical activities were also measured during a 48-hour period at baseline and at follow-up . Analysis of covariance was performed for the post-training outcome comparison . Results : Compared with the CG , the patients in the IG showed a significantly reduced CoM sway ( 58.31 % ; p = 0.009 ) , ankle sway ( 62.7 % ; p = 0.008 ) and hip joint sway ( 72.4 % ; p = 0.017 ) during the balance test with open eyes . The ankle sway was also significantly reduced in the IG group ( 58.8 % ; p = 0.037 ) during measurements while the eyes were closed . The number of steps walked showed a substantial but nonsignificant increase ( + 27.68 % ; p = 0.064 ) in the IG following training . Conclusion : The results of this r and omized controlled trial demonstrate that people with DPN can significantly improve their postural balance with diabetes-specific , tailored , sensor-based exercise training . The results promote the use of wearable technology in exercise training ; however , future studies comparing this technology with commercially available systems are required to evaluate the benefit of interactive visual joint movement feedback OBJECTIVE To evaluate the influence of a twice-weekly progressive resistance training ( PRT ) program , without a concomitant weight loss diet , on abdominal fat and insulin sensitivity in older men with type 2 diabetes . RESEARCH DESIGN AND METHODS Nine older men ( aged 66.6 + /- 3.1 ) with type 2 diabetes participated in a 16-week PRT supervised program ( 50 - 80 % of the one repetition maximum ) , for all main muscle groups . Basal glycemia , HbA(1c ) , diet , habitual physical activity , body composition , and upper/lower maximal strength were measured . Insulin sensitivity was determined according to Bergman 's minimal model procedure and abdominal fat was obtained by computed tomography . The measurements were taken 4 weeks before training ( -4 ) , immediately before training ( 0 ) , and at 8-week intervals ( i.e. , weeks 8 and 16 ) during the 16-week training period . RESULTS No significant variation was observed in any of the above selected parameters during the 4-week control period . After PRT , both leg and arm maximal strength increased significantly by 17.1 and 18.2 % , respectively . Visceral and subcutaneous abdominal fat decreased significantly by 10.3 % ( from 249.5 + /- 97.9 to 225.6 + /- 96.6 cm(3 ) , P < 0.01 ) and by 11.2 % ( from 356.0 + /- 127.5 to 308.6 + /- 118.8 cm(3 ) , P < 0.01 ) , respectively , while no changes were observed in body mass . PRT significantly increased insulin sensitivity by 46.3 % ( from 2.0 + /- 1.2 to 2.8 + /- 1.6 . 10(4 ) . min(-1 ) . muU(-1 ) . ml(-1 ) , P < 0.01 ) , whereas it significantly decreased ( -7.1 % , P < 0.05 ) fasting blood glucose ( from 146.6 + /- 28.3 to 135.0 + /- 29.3 mg/dl ) . Finally , a 15.5 % increase in energy intake ( from 2,287.1 + /- 354.7 to 2,619.0 + /- 472.1 kcal/day , P < 0.05 ) was observed . CONCLUSIONS Two sessions per week of PRT , without a concomitant weight loss diet , significantly improves insulin sensitivity and fasting glycemia and decreases abdominal fat in older men with type 2 diabetes BACKGROUND Diabetes in elderly adults is associated with an increased risk of fall . The aim of study was to determine whether a virtual reality exercise ( VRE ) program would improve balance , strength , gait , and falls efficacy in elderly adults with diabetes . SUBJECTS AND METHODS Fifty-five subjects with diabetes mellitus over 65 years of age were r and omly assigned to a VRE group ( VREG ) ( n=27 ) and a control group ( CG ) ( n=28 ) . The VREG received the VRE program and diabetes education , whereas the CG received only the diabetes education . The VRE program used video gaming ( PlayStation ( ® ) 2 ; Sony , Tokyo , Japan ) and was conducted for 50 min twice a week for 10 weeks . Balance , muscle strength , gait , and falls efficacy were measured at baseline and after intervention . Measurements were taken using a clinical tests ( the one-leg-st and ing test , the Berg Balance Scale , the functional reach test , the timed up- and -go test , and the sit-to-st and test ) , and gait analysis . A self-administered question naire was used to measure falls efficacy . RESULTS After training , the VREG showed significantly improved balance , decreased sit-to-st and times , and increased gait speed , cadence , and falls efficacy . CONCLUSIONS The VRE program was to maximize the effects of exercise by triggering players was to be fully immersed into the games and enhanced major influential factors on the falls of subject . This study suggests VRE programs are feasible and effective for reduced the risk of falls in elderly adults with type 2 diabetes OBJECTIVES to compare the incidence of recurrent falls in older people with and without diabetes , and to examine diabetes- and fall-related risk factors explaining the increased risk of recurrent falls associated with diabetes . METHODS population -based cohort study of 1,145 ( 85 with diabetes ) community-dwelling participants , aged ≥65 years , from The Longitudinal Aging Study Amsterdam ( LASA ) . Falls were assessed prospect ively ( every 3 months ) during a 3-year follow-up period . Incidence of recurrent falls was estimated with Poisson regression analyses . The associations between diabetes and time to recurrent falls , defined as at least two falls occurring within a 6-month period , and the potential explanatory role of several risk factors herein , were analysed with the use of Cox-regression models . RESULTS during a mean follow-up of 139 weeks , 30.6 % of the individuals with and 19.4 % of the individuals without diabetes fell recurrently [ incidence rate of 129.7 versus 77.4 per 1,000 persons-years , respectively , HR = 1.67 ( 95 % CI : 1.11 - 2.51 ) ] . Adjustments for potential confounders did not change the increased risk associated with diabetes [ HR = 1.63 ( 1.06 - 2.52 ) ] . Factors that partly explained this increased risk were : greater number of medication , higher levels of pain , poorer self-perceived health , lower physical activity and grip strength , more limitations in ADLs , lower-extremity physical performance and cognitive impairment . Altogether , these variables accounted for 47 % of the increased risk of recurrent falls associated with diabetes [ adjusted HR = 1.30 ( 0.79 - 2.11 ) ] . CONCLUSION fall prevention efforts targeting the factors identified above may need to be incorporated into the care and treatment of older individuals with diabetes Background Weight-bearing exercise has been discouraged for people with diabetes mellitus and peripheral neuropathy ( DM+PN ) . However , people with diabetes mellitus and insensate feet have an increased risk of falling . Lower-extremity exercise and balance training reduce fall risk in some older adults . It is unknown whether those with neuropathy experience similar benefits . Objective As part of a study of the effects of weight-bearing exercise on foot ulceration in people with DM+PN , the effects of a lower-extremity exercise and walking intervention on balance , lower-extremity strength ( force-generating capacity ) , and fall incidence were determined . Design The study was an observer-masked , 12-month r and omized controlled trial . Setting Part 1 of the intervention took place in physical therapy offices , and part 2 took place in the community . Patients The participants were 79 people who were mostly sedentary , who had DM+PN , and who were r and omly assigned to either a control group ( n=38 ) or an intervention group ( n=41 ) . Intervention Part 1 included leg strengthening and balance exercises and a graduated , self-monitored walking program ; part 2 included motivational telephone calls . Both groups received regular foot care , foot care education , and 8 sessions with a physical therapist . Measurements The measurements collected were strength , balance , and participant-reported falls for the year after enrollment . Results There were no statistically significant differences between the groups for falls during follow-up . At 12 months , there was a small increase in the amount of time that participants in the intervention group could st and on 1 leg with their eyes closed . No other strength or balance measurements differed between the groups . Limitations The study was design ed to detect differences in physical activity , not falls . The intensity of the intervention was insufficient to improve strength and balance in this population . Conclusions The training program had a minimal effect on participants ' balance and lower-extremity strength . Increasing weight-bearing activity did not alter the rate of falling for participants in the intervention group relative to that for participants in the control group . People who are sedentary and who have DM+PN appear to be able to increase activity without increasing their rate of falling The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials |
744 | 27,880,023 | An inclination for decreased static fracture strength could be observed after cyclic loading of all-ceramic single crowns and FDPs , but this was material specific . | PURPOSE The objective of this systematic review was to elaborate the aging effect of cyclic fatigue tests on mechanical durability of all-ceramic single crowns and fixed dental prostheses ( FDP ) . | The aim of this in vitro study was to evaluate the fracture load and marginal accuracy of crowns made from a shrinkage-free ZrSiO4 ceramic cemented with glass-ionomer or composite cement after chewing simulation . Thirty-two human m and ibular molars were r and omly divided into two groups . All teeth were prepared for and restored with shrinkage-free ZrSiO4 ceramic crowns ( Everest HPC , KaVo ) . The crowns of group A ( N = 16 ) were luted to the teeth using KetacCem and group B ( N = 16 ) were adhesively cemented using Panavia21EX . Measurements of the marginal accuracy before and after cementation were made using replicas and an image analysis system . All specimens were exposed to 1.2 million cycles of thermo-mechanical fatigue in a chewing simulator . Surviving specimens were subsequently loaded until fracture in a static testing device . Fracture loads ( N ) were recorded . All specimens survived chewing simulation . The mean fracture loads ( + /-s.d . ) were Group A , 1622 N ( + /-433 ) ; group B , 1957 N ( + /-806 ) . There was no significant difference between the two groups ( P > 0.05 ) . The marginal gap values before cementation were ( mean + /- s.d . ) : Group A , 32.7 microm ( + /-6.8 ) ; group B , 33.0 microm ( + /-6.7 ) . The mean marginal gap values after cementation were ( + /-s.d . ) : Group A , 44.6 microm ( + /-6.7 ) ; group B , 46.6 microm ( + /-7.7 ) . The marginal openings were significantly higher after cementation for both groups ( P < 0.05 ) . All test groups demonstrated fracture load and marginal accuracy values within the range of clinical acceptability PURPOSE This in vitro study investigated the marginal adaptation and fracture resistance of heat-pressed glass-ceramic and fiber-reinforced composite molar crowns luted with resin , resin-modified glass-ionomer , or zinc-oxide-eugenol-free cements . MATERIAL S AND METHODS A total of 24 heat-pressed all-ceramic and 24 glass fiber-reinforced composite crowns were constructed and cemented using the above-mentioned luting agents ( eight crowns per cement ) . The restorations were thermocycled and mechanically stressed , and fracture resistance was determined . Marginal adaptation was evaluated before and after stress application using semiquantitative analysis in a scanning electron microscope . RESULTS All-ceramic and fiber-reinforced composite crowns reached the highest fracture resistance after stress application in combination with the resin cement . When luted with resin-modified glass-ionomer or zinc-oxide-eugenol-free cements , the fracture resistance of all-ceramics decreased significantly , while the fiber-reinforced composite crowns maintained their fracture resistance level ; the lowest values were found for zinc-oxide-eugenol-free cements . The marginal adaptation remained unchanged after stress for all-ceramics and fiber-reinforced composite restorations if they were luted with resin cements . Luting with resin-modified glass-ionomers significantly deteriorated the marginal adaptation after stress application , with the exception of the crown-cement interface of all-ceramics . CONCLUSION The highest fracture resistance and marginal adaptation were found for all-ceramic and glass fiber-reinforced composite molar crowns if they were luted with resin cement BACKGROUND The authors analyzed the in vitro and in vivo performance of lithium disilicate glass-ceramic ( LDGC ) restorations and yttria-stabilized tetragonal zirconia polycrystalline ( Y-TZP ) ( that is , zirconium oxide ) restorations with regard to reliability , clinical performance and abrasion resistance . METHODS In the in vitro study , four authors subjected sample s of LDGC , Y-TZP and metal-ceramic crowns to step-stress fatigue testing . Four investigators assessed the in vivo clinical performance of LDGC and zirconium oxide-based restorations at four and seven years , respectively . In addition , one author conducted a r and omized , controlled clinical trial to analyze the volumetric loss of enamel and ceramic antagonist surfaces . RESULTS The LDGC crowns exhibited the highest fatigue load-to-failure values in the in vitro analysis . The results of the in vivo assessment showed that the clinical performance of the LDGC restorations at four years was comparable to that of the zirconium oxide-based crowns at seven years . The results of the in vivo , r and omized , controlled clinical trial showed that LDGC crowns were not only resistant to wear , but also were wear friendly to enamel antagonist surfaces . CONCLUSIONS The LDGC crowns in the in vitro and in vivo studies exhibited high durability , and they were wear friendly to opposing natural dentition . CLINICAL IMPLICATION S LDGC and zirconium oxide-based crowns are a clinical ly acceptable means of treating teeth that require full-coverage restorations . In addition , LDGC material s exhibit excellent clinical performance , as well as demonstrate acceptable abrasion compatibility with the opposing natural dentition STATEMENT OF PROBLEM The influence of different types of adhesive resin cements on the long-term prognosis of aluminum oxide ceramic posterior crowns is unclear . PURPOSE The purpose of this study was to evaluate the fracture resistance of aluminum oxide ceramic on maxillary posterior crowns cemented with different resin luting agents before and after cyclic thermomechanical loading . Material and methods Forty-eight maxillary first molars were prepared and restored with st and ardized aluminum oxide ceramic ( In-Ceram Alumina ) crowns . The test specimens were r and omly divided into 3 groups ( n=16 ) . The crowns were luted with an acrylic resin cement ( Super-Bond C&B , control , Group SB ) and 2 composite luting agents ( Panavia F , Group PV ; and Rely X Unicem , Group RX ) . Half of the specimens were exposed to thermomechanical fatigue in a masticatory simulator . All specimens were tested for fracture strength ( N ) using quasistatic loading . The Wilcoxon rank sum test was used to compare the fracture strength ( alpha=.05 ) . RESULTS All specimens survived the exposure to the simulator . The following median fracture strength values were obtained without/with thermomechanical fatigue loading : Group SB , 2726 N/2673 N ; Group PV , 2520 N/2083 N ; and Group RX , 2036 N/2369 N. The fracture strength in Group PV after thermomechanical fatigue loading was significantly lower compared to the fracture strength in Group PV without artificial aging ( P = .016 ) , as well as significantly lower compared to Group SB with artificial aging ( P = .003 ) . CONCLUSION Within the limitations of this study , all tested cements are capable of successfully luting aluminum oxide ceramic crowns . The fracture strength of Group PV after artificial aging was comparatively low The aim of the present study was to investigate the fracture resistance of zirconia crowns and to compare the results with crowns made of a material with known clinical performance ( alumina ) in away that reflects clinical aspects . Sixty crowns were made , 30 identical crowns of alumina and 30 of zirconia . Each group of 30 was r and omly divided into three groups of 10 crowns that were to undergo different treatments : ( i ) water storage only , ( ii ) pre-loading ( 10 000 cycles , 30 - 300 N , 1 Hz ) , ( iii ) thermocycling ( 5 - 55 degrees , 5000 cycles ) + pre-loading ( 10 000 cycles , 30 - 300 N , 1 Hz ) . Subsequently , all 60 crowns were subjected to load until fracture occurred . There were two types of fracture : total fracture and partial fracture . Fracture strengths ( N ) were : group 1 , alumina 905/zirconia 975 ( P = 0.38 ) ; group 2 , alumina 904/zirconia 1108 ( P < 0.007 ) and group 3 , alumina 917/zirconia 910 ( P > 0.05 ) . Total fractures were more frequent in the alumina group ( P < 0.01 ) . Within the limitations of this in vitro study , it can be concluded that there is no difference in fracture strength between crowns made with zirconia cores compared with those made of alumina if they are subjected to load without any cyclic pre-load or thermocycling . There is , however , a significant difference ( P = 0.01 ) in the fracture mode , suggesting that the zirconia core is stronger than the alumina core . Crowns made with zirconia cores have significantly higher fracture strengths after pre-loading PURPOSE Existing composite restorations on teeth are often remade prior to the cementation of fixed dental prostheses . The aim of this study was to evaluate the effect of static and cyclic loading on ceramic laminate veneers adhered to aged resin composite restorations . MATERIAL S AND METHODS Eighty sound maxillary incisors were collected and r and omly divided into four groups : group 1 : control group , no restorations ; group 2 : two Class III restorations ; group 3 : two Class IV restorations ; group 4 : complete composite substrate . St and ard composite restorations were made using a microhybrid resin composite ( Anterior Shine ) . Restored teeth were subjected to thermocycling ( 6000 cycles ) . Window preparations were made on the labial surface of the teeth for ceramic laminate fabrication ( Empress II ) . Teeth were conditioned using an etch- and -rinse system . Existing composite restorations representing the aged composites were silica coated ( CoJet ) and silanized ( ESPE-Sil ) . Ceramic laminates were cemented using a bis-GMA-based cement ( Variolink Veneer ) . The specimens were r and omly divided into two groups and were subjected to either static ( groups 1a , 2a , 3a , 4a ) or cyclic loading ( groups 1b , 2b , 3b , 4b ) . Failure type and location after loading were classified . Data were analyzed using one-way ANOVA and Tukey 's test . RESULTS Significantly higher fracture strength was obtained in group 4 ( 330 ± 81 N ) compared to the controls in group 1 ( 179 ± 120 N ) ( one-way ANOVA , p < 0.05 ) . Group 1b survived a lower mean number of cyclic loads ( 672,820 cycles ) than teeth of groups 2b to 4b ( 846x103 to 873x103 cycles ) . Failure type evaluation after the fracture test showed predominantly adhesive failures between dentin and cement , but after cyclic loading , more cohesive fractures in the ceramic were seen . CONCLUSION Ceramic laminate veneers bonded to conditioned aged composite restorations provided favorable results . Surface conditioning of existing restorations may eliminate the necessity of removing aged composite restorations |
745 | 19,277,913 | FDG-PET does not appear to be sufficiently accurate to be used in isolation for ruling out the presence of a primary tumour .
In lymph gl and staging , FDG-PET does not appear to be accurate enough to detect occult axillary metastases or micrometastases ( sensitivity 20 and 50 % , respectively ) ; sentinel node biopsy is required for confirmation .
In the detection of bone metastases , FDG-PET should be complemented with other tests such as bone gammagraphy or SPECT .
The assessment of response to chemotherapy , there seems to be no uniform criterion for establishing a st and ardized uptake value ( SUV ) for FDG that would allow responders and non-responders to be distinguished .
Conclusions FDG-PET is insufficiently sensitive to rule out small primary tumours .
Due to the high number of false positives returned , it can not replace axillary dissection in axillary lymph gl and staging .
A complete biochemical response identified by FDG-PET should not be relied upon to mean an absence of disease since the technique can not detect residual microscopic elements | Objetive To assess the safety and efficacy of FDG-PET in breast cancer in the diagnostic of primary tumours , lymph node staging , the detection of recurrent disease/metastases , and the assessment of chemotherapy treatment . | Background Positron emission tomography ( PET ) imaging using [18F]fluorodeoxyglucose ( 18F-FDG ) is recognized to have a major role in oncological imaging . Over recent years there has been a steady increase in the use of gamma camera PET ( GCPET ) systems as these are less expensive than dedicated PET scanners and facilitate the full range of nuclear medicine imaging . However , there is ongoing debate about their application and usefulness in the management of oncological patients . Objectives To assess the feasibility of GCPET in a nuclear medicine department in a district general hospital remote from a cyclotron , compared with other imaging modalities in demonstrating disease in patients with large or locally advanced breast cancer . Methods 18F-FDG was transported by road from a production unit 100 miles from the imaging department . Twenty-five patients ( mean age 68 years ) with primary breast tumours measuring ≥20 mm on clinical examination were studied . All patients underwent triple assessment prior to PET imaging with an ADAC Solus camera with molecular coincidence detection capability . Histopathology was obtained in 20 cases following surgery . Results GCPET detected 24/25 primary breast tumours ( sensitivity 96 % ) . This compared with 22/25 ( 88 % ) for ultrasound and 15/25 ( 60 % ) for mammography . The lesion missed by PET was a grade 1 tumour , 8 mm in size . Conclusion In this pilot study GCPET has been shown to be feasible in a district general hospital , enabling a limited on-site PET imaging service to be provided . In the cases studied it was more sensitive than mammography or ultrasonography . GCPET may provide additional information that could be important in planning the management of some patients with breast cancer Background The role of positron emission tomography ( PET ) scanning in determining the extent of disease in patients with breast cancer has not been defined . We investigated the utility of 18F-2-fluoro-2-deoxy-D-glucose (FDG)-PET scanning compared with conventional imaging with computed tomographic scanning and bone scanning in determining the extent of disease in patients with high-risk , operable breast cancer . Methods This was a prospect i ve study of patients who presented to Memorial Sloan-Kettering Cancer Center for operative treatment of breast cancer . Eighty eligible patients were enrolled and underwent computed tomographic chest , abdomen , pelvis , and bone scans , followed by FDG-PET . Changes in treatment based on scan findings were recorded by the operating surgeons . Imaging findings were verified by biopsy or long-term follow-up . Results Eight ( 10 % ) of 80 patients were found to have metastatic disease that was seen on both conventional imaging and PET . Four additional patients ( 5 % ) had additional foci of disease on PET that affected treatment decisions . No patient had findings on conventional imaging alone . Conventional imaging studies result ed in a higher number of findings that generated additional tests and biopsies that ultimately had negative results ( 17 % vs. 5 % for PET ) . There was a statistically significant difference in specificity for PET compared with conventional imaging ( P = .01 ) . Conclusions Conventional imaging and PET were equally sensitive in detecting metastatic disease in patients with high-risk , operable breast cancer , but PET generated fewer false-positive results . FDG-PET scanning should be further studied in this setting and considered in the preoperative evaluation of selected patients with breast cancer We sought to prospect ively assess the diagnostic performance of a high-resolution positron emission tomography ( PET ) scanner using mild breast compression ( positron emission mammography [ PEM ] ) . Data were collected on concomitant medical conditions to assess potential confounding factors . At four centers , 94 consecutive women with known breast cancer or suspicious breast lesions received 18F-fluorodeoxyglucose ( FDG ) intravenously , followed by PEM scans . Readers were provided clinical histories and x-ray mammograms ( when available ) . After excluding inevaluable cases and two cases of lymphoma , PEM readings were correlated with histopathology for 92 lesions in 77 women : 77 index lesions ( 42 malignant ) , 3 ipsilateral lesions ( 3 malignant ) , and 12 contralateral lesions ( 3 malignant ) . Of 48 cancers , 16 ( 33 % ) were clinical ly evident ; 11 ( 23 % ) were ductal carcinoma in situ ( DCIS ) , and 37 ( 77 % ) were invasive ( 30 ductal , 4 lobular , and 3 mixed ; median size 21 mm ) . PEM depicted 10 of 11 ( 91 % ) DCIS and 33 of 37 ( 89 % ) invasive cancers . PEM was positive in 1 of 2 T1a tumors , 4 of 6 T1b tumors , 7 of 7 T1c tumors , and 4 of 4 cases where tumor size was not available ( e.g. , no surgical follow-up ) . PEM sensitivity for detecting cancer was 90 % , specificity 86 % , positive predictive value ( PPV ) 88 % , negative predictive value ( NPV ) 88 % , accuracy 88 % , and area under the receiver-operating characteristic curve ( Az ) 0.918 . In three patients , cancer foci were identified only on PEM , significantly changing patient management . Excluding eight diabetic subjects and eight subjects whose lesions were characterized as clearly benign with conventional imaging , PEM sensitivity was 91 % , specificity 93 % , PPV 95 % , NPV 88 % , accuracy 92 % , and Az 0.949 when interpreted with mammographic and clinical findings . FDG PEM has high diagnostic accuracy for breast lesions , including DCIS The present study compared the diagnostic accuracy of fluorine-18 2-deoxy-2-fluoro-D-glucose positron emission tomography ( FDG-PET ) with conventional staging techniques . The differentiation between malignant and benign lesions and the detection of multifocal disease , axillary and internal lymph node involvement , and distant metastases were evaluated . One hundred and seventeen female patients were prospect ively examined using FDG-PET and conventional staging methods such as chest X-ray , ultrasonography of the breast and liver , mammography and bone scintigraphy . All patients were examined on a modern full-ring PET scanner . Histopathological analysis of resected specimens was employed as the reference method . The readers of FDG-PET were blinded to the results of the other imaging methods and to the site of the breast tumour . The sensitivity and specificity of FDG-PET in detecting malignant breast lesions were 93 % and 75 % respectively . FDG-PET was twofold more sensitive ( sensitivity 63 % , specificity 95 % ) in detecting multifocal lesions than the combination of mammography and ultrasonography ( sensitivity 32 % , specificity 93 % ) . Sensitivity and specificity of FDG-PET in detecting axillary lymph node metastases were 79 % and 92 % ( 41 % and 96 % for clinical evaluation ) . FDG-PET correctly indicated distant metastases in seven patients . False-positive or false-negative findings were not encountered with FDG-PET . Chest X-ray was false-negative in three of five patients with lung metastases . Bone scintigraphy was false-positive in four patients . Three patients were upstaged since FDG-PET detected distant metastases missed with the st and ard staging procedure . It is concluded that , compared with the imaging methods currently employed for initial staging , FDG-PET is as accurate in interpreting the primary tumour and more accurate in screening for lymph node metastases and distant metastases . Due to a false-negative rate of 20 % in detecting axillary lymph node metastases , FDG-PET can not replace histological evaluation of axillary status BACKGROUND The aim of this work is to assess the diagnostic value of positron emission tomography ( PET ) with 18F-fluorodeoxyglucose ( FDG ) , in the early detection of tumour recurrence in already treated breast cancer patients in apparent complete remission and with a progressive elevation of tumour markers CEA and /or CA 15.3 without any other clinical or instrumental signs of relapses . METHODS The author studied 45 women ( mean age 58+/-12 , range 35 - 80 years ) with histological diagnosis of breast cancer who underwent a tumour marker-guided whole body FDG-PET . All patients were in remission , without any other clinical or instrumental signs of relapses , except for the progressive elevation of CA 15.3 and /or CEA , tested during the follow-up . FDG-PET results were controlled by pathology when histological sampling was possible , by other conventional imaging modalities ( US , X-rays , CT , MRI ) and /or by clinical follow-up up to 12 months at least . RESULTS FDG-PET findings were evaluated in 38 patients : 27 result ed positive . Among these 27 PET positive patients 24 were true positive and 3 false positive . Tumour marker guided FDG-PET was also able to discover 3 unknown neoplasms not visualized by other modalities . PET revealed 54 sites of intense focal FDG uptake . The anatomical distribution of these sites was 19 skeleton , 18 lymph node basins , 5 liver , 5 pelvic region , 1 lung , 1 pericardium , 1 pleura , 1 contralateral breast , 2 peritoneum and 1 thyroid bed . Forty-eight of these 54 sites of FDG accumulation were confirmed to be metastases . FDG-PET result ed negative in 11 patients and only in 2 of them the other diagnostic modalities were able to discover metastatic lesions ; we had 9 true negative and 2 false positive RESULTS . On the basis of our investigation the performances of tumour marker guided FDG-PET per patient are as follows : sensitivity 92 % ( 24/26 ) , specificity 75 % ( 9/12 ) , positive predictive value 89 % ( 24/27 ) , negative predictive value 82 % ( 9/11 ) , accuracy 87 % ( 33/38 ) . CONCLUSIONS This study demonstrated the clinical utility of tumour marker-guided PET in the follow-up of breast cancer patients . This diagnostic approach allowed to modify the clinical management in those patients in whom a tumor relapse or unexpected primary neoplasm was discovered RATIONALE AND OBJECTIVES The authors performed this study to determine the feasibility of using quantitative 2-[fluorine-18]fluoro-2-deoxy-D-glucose ( FDG ) positron emission tomography ( PET ) to monitor the response of breast cancer bone metastases to therapy . MATERIAL S AND METHODS Twenty-four women with stage IV bone-dominant breast carcinoma were included in this study . Whole-body FDG PET imaging was performed at serial time points during the course of therapy . FDG PET scans were interpreted quantitatively by using the maximum st and ard uptake value ( SUV ) of the most conspicuous bone lesion at baseline FDG PET . PET results were compared to the overall assessment of response ( response , stable disease , progressive disease ) with a combination of conventional imaging , change in tumor marker values , and subjective symptom changes by experienced medical oncologists blinded to the findings at FDG PET . Changes in FDG SUV were also correlated quantitatively to the changes in a particular tumor marker ( CA 27.29 ) . RESULTS The changes in FDG SUV with therapy showed correlation with the overall clinical assessment of response ( P < .01 ) . The percentage change in FDG uptake with therapy showed strong correlation with the percentage change in tumor marker value ( P < .01 ) . CONCLUSION Preliminary results indicate that serial whole-body FDG PET can help quantitatively assess the response of breast cancer bone metastases to therapy . Prospect i ve trials are needed to further investigate its accuracy BACKGROUND Although axillary lymph node status is an important prognostic factor and axillary dissection is regarded as the gold st and ard for staging , it requires radical surgery which is accompanied by considerable postoperative problems such as lymphedema . This study was carried out to evaluate the diagnostic accuracy of preoperative positron emission tomography ( PET ) and intraoperative frozen biopsy of sentinel lymphadenectomy ( SLND ) in detecting axillary lymph node metastasis . METHODS We studied 18 patients who had preoperative PET and SLND for breast cancer in the Department of Surgery at Samsung Medical Center . They all had preoperative PET with a radiolabeled glucose analogue ( [18F]FDG ) to visualize primary tumors and metastatic nodes . Isosulphan blue dye was used for intraoperative SLND . Frozen and permanent biopsies were then compared after full axillary dissection . RESULTS In 18 cases , six had positive metastatic nodes in the permanent biopsy of full axillary dissection but were negative in three cases by preoperative PET . There was one false negative result by frozen biopsy of SLND which was later shown to be positive by permanent biopsy . The sensitivity and specificity of SLND and PET for detecting axillary node metastasis were 83 , 100 % and 50 , 100 % , respectively . CONCLUSION Although both methods are good for axillary nodal status , the intraoperative frozen biopsy result of SLND was superior to preoperative PET in our preliminary study Abstract . Presurgical neoadjuvant chemotherapy has shown promise in the treatment of locally advanced breast carcinoma ( LABC ) . Response assessment by clinical examination and mammography is difficult . This study evaluated and compared fluorine-18 fluorodeoxyglucose positron emission tomography ( 18F-FDG-PET ) and technetium-99 m sestamibi scintimammography ( SMM ) as potential methods for the early assessment of tumour response to neoadjuvant chemotherapy in patients with LABC . Seven patients underwent PET and SMM [ planar and single-photon emission tomography ( SPET ) ] before beginning chemotherapy , after the first and second cycles of chemotherapy and after completing chemotherapy prior to surgery . PET and SMM results were evaluated visually and semi-quantitatively by calculating st and ardised uptake values ( SUV ) and tumour/lung ratios in the initial and subsequent studies . The findings were correlated with the initial clinical and mammographic findings and the final histopathological diagnoses . There was a highly significant correlation between SUVmean , SUVmax and the tumour/lung ratio determined with SMM-SPET in the studies performed before and during neoadjuvant chemotherapy . All three patients with complete remission showed decreasing FDG and sestamibi uptake as early as 8 days after therapy . In the presurgical study , increased sestamibi and FDG uptake was no longer evident . Three patients had partial remission with clearly reduced but persisting focal FDG and sestamibi uptake after neoadjuvant therapy . One patient who did not respond to therapy had unchanged intense tracer uptake during chemotherapy that was evident with both techniques . An early decline in glucose metabolism or sestamibi uptake 8 days after beginning therapy did not necessarily predict complete tumour remission in the further course of chemotherapy . On the other h and , increased tracer uptake after the first cycle did not exclude a partial tumour response . After the second chemotherapeutic cycle both techniques were able to distinguish between complete and partial/no response . There was a good correlation between preoperative FDG and sestamibi uptake and the histopathologically determined tumour size . However , small residual invasive tumours in patients with clinical ly complete remission could not be visualised with either technique . The preliminary data demonstrate that sestamibi SMM is as useful as FDG-PET for the monitoring of tumour response to neoadjuvant chemotherapy We prospect ively evaluated 31 patients with invasive breast cancer . Preoperative positron emission tomography ( PET ) with 18F-fluoro-2-deoxy-D-glucose ( 18F-FDG ) for detection of axillary lymph node metastases was compared with the histopathologic status of the sentinel lymph node ( SLN ) . Sensitivity of PET imaging was 43 % , specificity and negative predictive value were 94 and 67 % , respectively . The smallest metastasis detected by PET measured 3 mm in diameter . The results of this study suggest that detection of small axillary lymph node metastases is limited by the currently achievable spatial resolution of PET imaging . Selective axillary surgery in breast cancer patients based on 18F-FDG PET is yet not possible Background : Positron emission tomography ( PET ) is a noninvasive imaging modality that can detect malignant lymph nodes . This study determined the sensitivity , specificity , predictive values , and likelihood ratios of PET scanning compared with st and ard axillary lymph node dissection ( ALND ) and sentinel lymph node biopsy ( SLNB ) in staging the axilla in women with early stage breast cancer . Methods : Women with clinical stage I or II breast cancer had whole body PET scanning before ALND and SLNB , in a prospect i ve , blinded protocol . ALND were evaluated by st and ard hematoxylin and eosin ( H&E ) staining techniques , while sentinel nodes were also examined for micrometastatic disease . Results : A total of 98 patients were recruited . PET compared with ALND demonstrated sensitivity of 0.40 ( 95 % CI , 0.16 , 0.68 ) , specificity 0.97 ( CI , 0.90 , 0.99 ) , positive likelihood ratio 14.4 ( CI , 3.21 , 64.5 ) , positive predictive value 0.75 ( CI , 0.35 , 0.97 ) , and false – negative rate of 0.60 ( CI , 0.32 , 0.84 ) . Test properties were similar for PET compared with sentinel nodes positive by H&E staining . A few false – positive scans ( 0.028 , CI , 0.003 , 0.097 ) were seen . Multiple logistic regression analysis found that PET accuracy was better in patients with high grade and larger tumors . Increased size and number of positive nodes were also associated with a positive PET scan . Conclusions : The sensitivity of PET compared with ALND and SLNB was low , whereas PET scanning had high specificity and positive predictive values . The study suggests that PET scanning can not replace histologic staging in early stage breast cancer . The low rate of false – positive findings suggests that PET can identify women who can forego SLNB and require full axillary dissection Magnetic resonance ( MR ) imaging after ultra-small super paramagnetic iron oxide ( USPIO ) injection and 18F-fluorodeoxyglucose positron emission tomography ( FDG-PET ) for preoperative axillary lymph node staging in patients with breast cancer were evaluated using histopathologic findings as the reference st and ard . USPIO-enhanced MR and FDG-PET were performed in ten patients with breast cancer who were scheduled for surgery and axillary node resection . T2-weighted fast spin echo , T1-weighted three-dimensional ( 3D ) gradient echo , T2 * -weighted gradient echo and gadolinium-enhanced T1-weighted 3D gradient echo with spectral fat saturation were evaluated . MR imaging before USPIO infusion was not performed . The results were correlated with FDG-PET ( acquired with dedicated PET camera , visual analysis ) and histological findings . The histopathologic axillary staging was negative for nodal malignancy in five patients and positive in the remaining five patients . There was one false positive finding for USPIO-enhanced MR and one false negative finding for FDG-PET . A sensitivity ( true positive rate ) of 100 % , specificity ( true negative rate ) of 80 % , positive predictive value of 80 % , and negative predictive value of 100 % were achieved for USPIO-enhanced MR and of 80 % , 100 % , 100 % , 80 % for FDG-PET , respectively . The most useful sequences in the detection of invaded lymph nodes were in the decreasing order : gadolinium-enhanced T1-weighted 3D gradient echo with fat saturation , T2 * -weighted 2D gradient echo , T1-weighted 3D gradient echo and T2-weighted 2D spin echo . In our study , USPIO-enhanced T1 gradient echo after gadolinium injection and fat saturation emerged as a very useful sequence in the staging of lymph nodes . The combination of USPIO-enhanced MR and FDG-PET achieved 100 % sensitivity , specificity , PPV and NPV . If these results are confirmed , the combination of USPIO MR with FDG-PET has the potential to identify the patient c and i date s for axillary dissection versus sentinel node lymphadenectomy PURPOSE The aim of this work is to compare the accuracy of non-attenuation-corrected ( NAC ) and attenuation-corrected ( AC ) PET images using 2-deoxy-2-[18F]fluoro-D-glucose ( FDG ) in assessment of the axilla in patients with newly-diagnosed , untreated , primary breast cancers , and to determine the frequency of extra-axillary findings . PATIENTS AND METHODS FDG-PET was performed in 36 patients with breast cancer one hour following the intravenous injection of approximately 370 MBq of FDG . Patients were imaged prior to axillary dissection to prospect ively confirm the presence or absence of axillary metastases . NAC and AC images were separately and independently review ed in a blinded fashion by two readers . Imaging results were compared with final diagnoses obtained by surgery and pathology . RESULTS Ninety-six positive axillary lymph nodes in 15 patients were histopathologically confirmed by surgery . The average areas under the ROC curve for NAC and AC image were 0.682 and 0.721 , respectively . In patient-based analysis , the sensitivity in interpreting NAC images for the presence of metastases was low ( 53.3 % ) and comparable to that of AC images ( 46.7 % ) . The specificity of NAC image was high ( 85.7 % ) , but tended to be lower than that in AC ( 95.2 % ) . The overall diagnostic accuracy for detecting axillary involvement in AC images ( 75.0 % ) was comparable to that of NAC images ( 72.2 % ) . Extra-axillary disease was found in three patients . CONCLUSION NAC images were comparable to AC images , although there were more false positive results with the NAC images . While AC PET has high specificity in this application , it appears insufficiently sensitive to use these methods to avoid axillary tissue sampling , when negative . Extra-axillary findings , while infrequent , may be quite important . Examination of both NAC and AC images is advised when assessing possible metastatic breast cancer to the axilla using PET METHODS The presurgical , noninvasive staging of axillary nodes for metastases was prospect ively investigated in 68 patients who were diagnosed with primary breast cancer using PET with 18F-fluorodeoxyglucose ( FDG ) . Four patients had bilateral nodules ; therefore , the total number of evaluable cases was 72 . Visual analyses of attenuation-corrected PET images and st and ardized uptake values ( SUVs ) of FDG uptake in carcinomas were compared with histopathological surgical findings . The SUV distribution differences between carcinomas with and without axillary metastases were evaluated by means of statistical and receiver operating characteristics analyses . RESULTS PET correctly classified 64 of the 72 cases ; four false-positive and four false-negative PET results were found . The overall sensitivity , specificity and accuracy of PET for axillary metastases were 85 % , 91 % and 89 % , respectively . With respect to the clinical axillary stage of the patients ( TNM , or tumor-node-metastasis , classification ) , we obtained the following results : N0 patients , sensitivity = 70 % , specificity = 92 % , accuracy = 86 % ; N1a patients , sensitivity = 85.5 % , specificity = 100 % , accuracy = 95 % ; and N1b-2 patients , sensitivity = 100 % , specificity = 67 % , accuracy = 87 % . The median SUV in carcinomas with axillary metastases ( 4.6 ) was significantly higher than that in carcinomas without metastases ( 2.9 ) , but there was a great SUV overlap between the two groups ( interquartile ranges = 2.7 - 7.2 and 1.9 - 4.5 , respectively ) . Analysis of the receiver operating characteristics curve showed that a high sensitivity of SUV in predicting axillary metastases was associated with a very low specificity and vice versa . With the best SUV cutoff value of 2.9 , the sensitivity and specificity were 74 % and 56 % , respectively . CONCLUSION PET showed good overall diagnostic accuracy in the detection of axillary metastases ( 86 % ) . The very high accuracy ( 95 % ) in N1a patients is of particular importance . False-negative PET findings , however , can be encountered . SUVs of breast carcinoma can not predict the spread of the disease to the axilla , even if higher values are often associated with axillary metastases . Any decision on the use of PET in the presurgical staging of breast cancer should be incorporated into a more general debate on axillary management . In selected patients with a very low probability of axillary metastases ( T1a ) , in whom axillary surgery can already be avoided according to data from follow-up studies , 18F-FDG PET could be proposed as a noninvasive imaging modality to improve the diagnosis of axillary relapses The presence of internal mammary ( IM ) lymph node metastases in breast cancer predicts outcome and may alter treatment . St and ard imaging has limited usefulness for evaluation of the IM chain because of low sensitivity . Our preliminary studies suggested that [F-18]-2-fluoro-d-glucose positron emission tomography ( FDG-PET ) improves the detection of IM and mediastinal metastases . We therefore performed a retrospective review of women who underwent FDG-PET prior to treatment to determine the benefit of PET for imaging IM disease . The records of 28 consecutive patients undergoing FDG-PET prior to neoadjuvant chemotherapy for suspected locally advanced breast cancer ( LABC ) were review ed . The presence of abnormal IM uptake on FDG-PET was noted . IM uptake on FDG PET was compared with st and ard radiographic imaging and was correlated with putative risk factors for IM involvement and with clinical patterns of failure . Patients did not undergo IM biopsy ; however , patterns of failure were assessed to vali date the FDG-PET findings . Clearly abnormal FDG uptake in the IM nodes was seen in 7 of 28 women ( 25 % ) . Prospect i ve conventional chest imaging failed to identify IM metastases in any patient . IM uptake on PET was associated with large size of the primary tumor ( P = 0.03 ) and with inflammatory disease ( P = 0.04 ) . The presence of IM FDG uptake predicted failure by a pattern consistent with spread from IM lymph node metastasis . FDG-PET appears to be a useful noninvasive modality to detect IM metastases in LABC . Pathologic verification in a prospect i ve study is necessary to confirm these findings PURPOSE To determine the accuracy of positron emission tomography with fluorine-18-labeled 2-fluoro-2-deoxy-d-glucose ( FDG-PET ) in detecting axillary nodal metastases in women with primary breast cancer . PATIENTS AND METHODS In this prospect i ve multicenter study , 360 women with newly diagnosed invasive breast cancer underwent FDG-PET . Images were blindly interpreted by three experienced readers for abnormally increased axillary FDG uptake . Imaging results from 308 assessable axillae were compared with axillary node pathology . RESULTS For detecting axillary nodal metastasis , the mean estimated area under the receiver operator curve for the three readers was 0.74 ( range , 0.70 to 0.76 ) . If at least one probably or definitely abnormal axillary focus was considered positive , the mean ( and range ) sensitivity , specificity , and positive and negative predictive values for PET were 61 % ( 54 % to 67 % ) , 80 % ( 79 % to 81 % ) , 62 % ( 60 % to 64 % ) , and 79 % ( 76 % to 81 % ) , respectively . False-negative axillae on PET had significantly smaller and fewer tumor-positive lymph nodes ( 2.7 ) than true-positive axillae ( 5.1 ; P < .005 ) . Semiquantitative analysis of axillary FDG uptake showed that a nodal st and ardized uptake value ( lean body mass ) more than 1.8 had a positive predictive value of 90 % , but a sensitivity of only 32 % . Finding two or more intense foci of tracer uptake in the axilla was highly predictive of axillary metastasis ( 78 % to 83 % positive predictive value ) , albeit insensitive ( 27 % ) . CONCLUSION FDG-PET has moderate accuracy for detecting axillary metastasis but often fails to detect axillae with small and few nodal metastases . Although highly predictive for nodal tumor involvement when multiple intense foci of tracer uptake are identified , FDG-PET is not routinely recommended for axillary staging of patients with newly diagnosed breast cancer BACKGROUND The aim of this prospect i ve study was to evaluate the predictive value of [18F]fluorodeoxyglucose positron emission tomography ( FDG PET ) for the pathological response of breast cancer after completion of neo-adjuvant chemotherapy . METHODS Fifty patients with newly diagnosed , non-inflammatory , large or locally advanced breast cancer undergoing neo-adjuvant chemotherapy were eligible for this study . Clinical assessment was accomplished by comparing initial tumor size with preoperative tumor size . Pathological responses were classified into three groups : pathological non-response ( pNR ) , pathological partial response ( pPR ) and pathological complete response ( pCR ) . To determine the effect of reduction rate ( RR ) of peak st and ardized uptake values for tumor responses , logistic regression analyses were performed . To identify an optimal threshold value of RR for the prediction of pathological response , receiver operating characteristic analysis was performed . RESULTS Eight per cent ( four of 50 ) of the patients had pCR and 46 % had pPR . Ten per cent of patients had clinical CR and 52 % had clinical PR . In clinical response , the RRs ( + /- SD ) of CR ( -83.4 + /- 12 ) , PR ( -81.8 + /- 22.7 ) and NR ( -79.7 + /- 31.9 ) showed no statistical differences ( P > 0.05 ) . However , for pathological responses , the RR of CR ( -96.5 + /- 3.4 ) had a lower value than those of PR ( -87.9 + /- 15.1 ) and NR ( -56.2 + /- 29.6 ) ( P = 0.0006 ; CR versus PR , P < 0.05 ; CR versus NR , P < 0.05 ; PR versus NR , P < 0.01 ) . When -88 % of RR was used as threshold value for differentiation between pCR and pPR , the area under the curve ( AUC ) was 0.788 [ st and ard error ( SE ) 0.106 ; 95 % confidence interval ( CI ) 0.589 - 0.920 ] . The sensitivity and specificity were 100 % and 56.5 % , respectively . When -79 % of RR was used as threshold value for differentiation between pathological responders and non-responders , the AUC was 0.838 ( SE 0.059 ; 95 % CI 0.707 - 0.927 ) . The sensitivity and specificity were 85.2 % and 82.6 % , respectively . CONCLUSIONS Despite some limitations , this study suggests a possible predictive value of FDG PET for the assessment of the pathological response of primary breast cancer after neo-adjuvant chemotherapy . However , these findings deserve further investigation on a larger number of patients , and more frequent and earlier PET scans in each patient need to be performed to allow a better validation of the differentiation between the responder and non-responder groups BACKGROUND The aim of this study was to investigate the diagnostic value of FDG PET in the follow-up for breast cancer in disease-free patients and patients suspected of having recurrent or metastatic disease . As a single imaging tool , PET can be compared with the conventional diagnostic means used for different examination sites . PATIENTS AND METHODS A total of 73 PET studies were carried out on 57 patients who had been diagnosed as having breast cancer . Sixteen patients had two PET scans . Thirty-eight scans ( 52.% ) were performed in a follow-up setting . Thirty-five PET scans were performed in patients suspected of having recurrent disease or elevated tumor marker . Depending on the region of suspicion , conventional imaging included computed tomography , magnetic resonance imaging , chest X-ray , ultrasound and X-ray . All the patients in our study were followed-up for a period of 12 months . RESULTS PET correctly identified metastatic or recurrent disease in 25 out 27 cases of clinical suspicion . In patients examined because of elevated tumour marker CA 15 - 3 , PET was able to detect recurrence or metastatic disease in six of the eight patients . The absence of disease was correctly diagnosed by PET in 35 out of 38 scans in 24 patients in the follow-up for breast cancer . The overall sensitivity and specificity for PET was 80.6 % and 97.6 % , respectively . On the basis of a yearly rate of disease progression of 5 - 8 % , the mean positive predictive value was 74.5 % and the mean negative predictive value 98.3 % . CONCLUSION PET has been shown to have impact on the staging and management of recurrent or metastatic breast cancer in cases of suspicion and in a follow-up setting . The current oncological situation can be clarified with a single basic imaging modality The aim of this prospect i ve study was to evaluate the role of fluorodeoxyglucose positron emission tomography ( FDG‐PET ) in the staging of high‐risk women with primary or recurrent breast cancer Objective To prospect ively investigate determinants of the accuracy of staging axillary lymph nodes in breast cancer using [F-18]fluorodeoxyglucose positron emission tomography ( FDG PET ) . Methods Patients with primary operable breast cancer underwent FDG PET of the chest followed by sentinel node biopsy ( SNB , n = 47 ) and /or complete axillary lymph node dissection ( ALND , n = 23 ) . PET scans were independently interpreted by three observers in a blinded fashion with respect to the FDG avidity of the primary tumor and the axillary status . The results were compared to histopathological analyses of the axillary lymph nodes . Clinicians were blinded to the PET results . Results Axillary lymph node specimens and FDG PET scans were evaluated in 70 patients ( 59 % cT1 ) . Overall , 32 ( 46 % ) had lymph node metastases as established by SNB ( 18/47 ) or ALND ( 14/23 ) , 20 of which were confined to a single node . The overall sensitivity of FDG PET was 25 % , with a specificity of 97 % . PET results were false-negative in all 18 positive SNBs and true-positive in 8/14 in the ALND group . The performance of FDG PET depended on the axillary tumor load and the FDG avidity of the primary tumor . Intense uptake in the primary tumor was found in only 57 % of the patients , and this was independent of the size . There was excellent interobserver agreement of visual assessment of FDG uptake in primary tumor and axillary lymph nodes . Conclusions The sensitivity of FDG PET to detect occult axillary metastases in operable breast cancer was low , and it was a function of axillary tumor load and FDG avidity of the primary tumor . Even though the clinical relevance of occult disease detected by SNB needs to be confirmed , it is suggested that FDG PET in these patients should be focused on exploiting its nearly perfect specificity and the potential prognostic relevance of variable FDG uptake PURPOSE To evaluate the diagnostic value of positron emission tomography ( PET ) using fluorine-18 fluorodeoxyglucose ( FDG ) for the diagnosis of primary breast cancer . PATIENTS AND METHODS Preoperatively , 144 patients with masses suggestive of breast cancer underwent PET imaging of the breast . To identify breast cancer by increased metabolic activity , parametric FDG-PET images were analyzed for increased tracer uptake applying conventional image reading ( CIR ) and sensitive image reading ( SIR ) . One hundred eighty-five breast tumors were evaluated by histology , revealing 132 breast carcinomas and 53 benign masses . RESULTS Breast carcinomas were identified with an overall sensitivity of 64.4 % ( CIR ) and 80.3 % ( SIR ) . The increase in sensitivity ( SIR ) result ed in a noticeable decrease in specificity , from 94.3 % ( CIR ) to 75.5 % ( SIR ) . At stage pT1 , only 30 ( 68.2 % ) of 44 breast carcinomas were detected , compared with 57 ( 91.9 % ) of 62 at stage pT2 . A higher percentage of invasive lobular carcinomas were false-negative ( 65.2 % ) compared with invasive ductal carcinomas ( 23.7 % ) . Nevertheless , positive PET scans provided a high positive-predictive value ( 96.6 % ) for breast cancer . CONCLUSION Partial volume effects and varying metabolic activity ( dependent on tumor type ) seem to represent the most significant limitations for the routine diagnostic application of PET . The number of invasive procedures is therefore unlikely to be significantly reduced by PET imaging in patients presenting with abnormal mammography . However , the high positive-predictive value , result ing from the increased metabolic activity of malignant tissue , may be used with carefully selected subsets of patients as well as to determine the extent of disease or to assess therapy response Background FDG PET has not yet found a role in the clinical evaluation of the tumor extent of breast cancer . FDG PET has been reported to be useful for evaluating the prognoses of breast cancer patients with more accuracy than conventional imaging modalities . The purpose of this study was to compare the accuracy of FDG PET and MRI for the preoperative assessment of the tumor extent of breast cancer , for evaluating the impact of FDG PET on systemic staging , and also for predicting the prognosis of patients who are c and i date s for breast-conserving therapy . Methods The study was a prospect i ve series of 23 breasts with breast cancer that underwent both FDG PET and MRI before surgery . Systemic staging with FDG PET was also performed . The correlation between the results of these examinations and histological findings was thus examined . The maximum st and ardized uptake value ( SUVmax ) of the tumors was investigated in association with the patient prognoses . Results When evaluating the local tumor extent , the accuracy of FDG PET ( 43.5 % ) was significantly lower than that of MRI ( 91 % ) ( P < 0.001 ) . The sensitivity , specificity , and accuracy of FDG PET regarding the nodal status were 60 , 94 , and 87 % , respectively . No patients demonstrated any distant metastasis , whereas FDG PET gave a false positive in one patient . The mean follow-up period was 61 months . The SUVmax value of the worse prognosis patient group was significantly higher than that of the good prognosis patient group ( P = 0.032 ) . Conclusions FDG PET is not a breast imaging modality for evaluating the local tumor extent , but it is useful for predicting the prognoses of patients who are c and i date s for breast-conserving therapy |
746 | 31,734,106 | There was a lack of evidence to support any one type of intervention being effective to prevent depression in universal or targeted primary or secondary setting s. Comparison-adjusted funnel plots suggest the presence of small- study effects for the universal secondary anxiety analysis .
INTERPRETATION Considering unclear risk of bias and probable small study effects for anxiety , we conclude there is little evidence that educational setting -based interventions focused solely on the prevention of depression or anxiety are effective . | BACKGROUND Rates of anxiety and depression are increasing among children and young people .
Recent policies have focused on primary prevention of mental disorders in children and young people , with schools at the forefront of implementation .
There is limited information for the comparative effectiveness of the multiple interventions available . | Adolescent anxiety is debilitating , the most frequently diagnosed adolescent mental health problem , and leads to substantial long-term problems . A r and omized controlled trial ( n = 138 ) was conducted to test the effectiveness of a biofeedback video game ( Dojo ) for adolescents with elevated levels of anxiety . Adolescents ( 11–15 years old ) were r and omly assigned to play Dojo or a control game ( Rayman 2 : The Great Escape ) . Initial screening for anxiety was done on 1,347 adolescents in five high schools ; only adolescents who scored above the “ at-risk ” cut-off on the Spence Children Anxiety Survey were eligible . Adolescents ’ anxiety levels were assessed at pre-test , post-test , and at three month follow-up to examine the extent to which playing Dojo decreased adolescents ’ anxiety . The present study revealed equal improvements in anxiety symptoms in both conditions at follow-up and no differences between Dojo and the closely matched control game condition . Latent growth curve models did reveal a steeper decrease of personalized anxiety symptoms ( not of total anxiety symptoms ) in the Dojo condition compared to the control condition . Moderation analyses did not show any differences in outcomes between boys and girls nor did age differentiate outcomes . The present results are of importance for prevention science , as this was the first full-scale r and omized controlled trial testing indicated prevention effects of a video game aim ed at reducing anxiety . Future research should carefully consider the choice of control condition and outcome measurements , address the potentially high impact of participants ’ expectations , and take critical design issues into consideration , such as individual- versus group-based intervention and contamination issues Background Depression often emerges for the first time during adolescence . There is accumulating evidence that universal depression prevention programs may have the capacity to reduce the impact of depression when delivered in the school environment . Objective This trial investigated the effectiveness of SPARX-R , a gamified online cognitive behavior therapy intervention for the prevention of depression relative to an attention-matched control intervention delivered to students prior to facing a significant stressor — final secondary school exams . It was hypothesized that delivering a prevention intervention in advance of a stressor would reduce depressive symptoms relative to the control group . Methods A cluster r and omized controlled trial was conducted in 10 government schools in Sydney , Australia . Participants were 540 final year secondary students ( mean 16.7 [ SD 0.51 ] years ) , and clusters at the school level were r and omly allocated to SPARX-R or the control intervention . Interventions were delivered weekly in 7 modules , each taking approximately 20 to 30 minutes to complete . The primary outcome was symptoms of depression as measured by the Major Depression Inventory . Intention-to-treat analyses were performed . Results Compared to controls , participants in the SPARX-R condition ( n=242 ) showed significantly reduced depression symptoms relative to the control ( n=298 ) at post-intervention ( Cohen d=0.29 ) and 6 months post-baseline ( d=0.21 ) but not at 18 months post-baseline ( d=0.33 ) . Conclusions This is the first trial to demonstrate a preventive effect on depressive symptoms prior to a significant and universal stressor in adolescents . It demonstrates that an online intervention delivered in advance of a stressful experience can reduce the impact of such an event on the potential development or exacerbation of depression . Trial Registration Australian New Zeal and Clinical Trials Registry ACTRN12614000316606 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?id=365986 ( Archived by WebCite at http://www.webcitation.org/ 6u7ou1aI9 BACKGROUND Children with anxious or depressive symptoms are at risk of developing internalizing disorders and their attendant morbidity . To prevent these outcomes , school-based cognitive-behavioral therapy ( CBT ) has been developed , but few studies include active control conditions . We evaluated a preventive CBT program targeting internalizing symptoms relative to an activity contrast condition post-intervention and at 1-year follow-up . METHODS One thous and one hundred and thirty-nine children from Grade s 3 - 6 from a diverse sample of schools , were screened with the Multidimensional Anxiety Scale for Children and Children 's Depression Inventory . Those with t>60 on either measure were offered participation in a r and omized 12-week trial , school-based group CBT versus a structured after-school activity group of equal duration . We explored several therapeutic elements as potential predictors of change . RESULTS One hundred and forty-eight children participated ( 84 boys , 64 girls ; 78 CBT , 70 contrast ; 57 % Caucasian ) and 145 completed the program . Self-reported anxious and depressive symptoms decreased significantly over time ( η(2)=.15 and .133 , respectively ) , with no group by time interaction . There was a trend toward fewer children meeting diagnostic criteria for an anxiety disorder on the Anxiety Disorders Interview Schedule at 1-year post-CBT than post-contrast ( 6/76 versus 12/69 ) . Positive reinforcement of child behavior was associated with change in anxiety symptoms ; checking homework was understood with change in depressive symptoms . CONCLUSIONS Findings suggest that children with internalizing symptoms may benefit from both school-based CBT and structured activity programs . Replication , longer follow-up , and further studies of therapeutic elements in child CBT are indicated . IS RCT N Registry identifier : IS RCT N88858028 , url : Although few prevention studies have been design ed to investigate the course of prevention effects over time , it seems that the effects on depressive symptoms increase from post-intervention to 6-month follow-up but then decrease with longer lags to follow-up . Furthermore , previous prevention studies have found differential intervention effects for boys and girls without testing possible explanations for this effect . The present r and omized control group study with 301 8th- grade students examined the effects of a depression prevention program from baseline until 12-month follow-up . As expected , while positive intervention effects were found on girls ' depressive symptoms , no such effects were found on boys ' depressive symptoms . Further , the positive intervention effects on girls ' depressive symptoms increased to the 6-month follow-up and remained stable through the 12-month follow-up , while depression symptoms in control-group girls increased from 6-month to 12-month follow-up . Further exploratory analyses revealed that neither baseline conduct problems nor cognitive or social knowledge of the prevention program at 12-month follow-up alone explained the sex effect . However , some limited evidence was found indicating that total knowledge ( cognitive and social ) might partially explain the effect but there was significant variability remaining to be explained BACKGROUND Anxiety in children is common , impairs everyday functioning , and increases the risk of severe mental health disorders in adulthood . We investigated the effect of a classroom-based cognitive behaviour therapy prevention programme ( FRIENDS ) on anxiety symptoms in children . METHODS Preventing Anxiety in Children though Education in Schools ( PACES ) is a three-group parallel cluster r and omised controlled trial . Interventions were given between September , 2011 , and July , 2012 , with schools as the unit of allocation and individual participants as the unit of analysis . We enrolled state-funded junior schools in southwest Engl and . We sent information to all eligible schools ( state-funded junior schools in southwest Engl and ) inviting them to enrol in the study . School year groups were assigned by computer-generated r and omisation ( 1:1:1 ) to receive either school-led FRIENDS ( led by teacher or school staff member ) , health-led FRIENDS ( led by two trained health facilitators ) , or usual school provision . Children were not masked to treatment allocation . The allocated programme was given to all students ( aged 9 - 10 years ) in the school year ( ie , universal delivery ) as part of the school curriculum as nine , 60 min weekly sessions . Outcomes were collected by self-completed question naire administered by research ers masked to allocation . Primary outcome was symptoms of anxiety and low mood at 12 months assessed by the Revised Child Anxiety and Depression Scale ( RCADS 30 ) . Analyses were intention to treat and accounted for the clustered nature of the design . The study is registered , number IS RCT N23563048 . FINDINGS 45 schools were enrolled : 14 ( n=497 children ) were r and omly assigned to school-led FRIENDS , 14 ( n=509 ) to health-led FRIENDS , and 12 ( n=442 ) to usual school provision . 1257 ( 92 % ) children completed 12 month assessment s ( 449 in health-led FRIENDS , 436 in school-led FRIENDS , and 372 in usual school provision ) . We recorded a difference at 12 months in adjusted mean child-reported RCADS scores for health-led versus school-led FRIENDS ( 19·49 [ SD 14·81 ] vs 22·86 [ 15·24 ] ; adjusted difference -3·91 , 95 % CI -6·48 to -1·35 ; p=0·0004 ) and health-led FRIENDS versus usual school provision ( 19·49 [ 14·81 ] vs 22·48 [ 15·74 ] ; -2·66 , -5·22 to -0·09 ; p=0·043 ) . We noted no differences in parent or teacher ratings . Training teachers to deliver mental health programmes was not as effective as delivery by health professionals . INTERPRETATION Universally delivered anxiety prevention programmes can be effective when used in schools . However , programme effectiveness varies depending on who delivers them . FUNDING National Institute for Health Research Public Health Research Programme PURPOSE Although cognitive-behavioral interventions have been successful in treating depression , no studies were found that focused solely on reducing negative thinking via group intervention as a means of preventing depression in at-risk groups . The purpose of this r and omized controlled trial was to test the effectiveness of a cognitive-behavioral group intervention in reducing depressive symptoms , decreasing negative thinking , and enhancing self-esteem in young women at risk for depression . DESIGN A r and omized controlled trial with 92 college women ages 18 to 24 who were at risk for depression was conducted . METHOD Participants were r and omly assigned to either the control or experimental group . The experimental group participated in a 6-week cognitive-behavioral group intervention . Data on self-esteem , depressive symptoms , and negative thinking were collected via self-report question naires from control and experimental groups at baseline , 1 month after the intervention , and at 6-month follow-up . Data were analyzed using mixed-model methodology and the Cochran-Mantel-Haenszel chi-square test . FINDINGS Compared to those in the control group , women who received the intervention had a greater decrease in depressive symptoms and negative thinking and a greater increase in self-esteem , and these beneficial effects were maintained over 6-months . CONCLUSIONS The findings document the effectiveness of this cognitive-behavioral group intervention and indicate empirical support for the beneficial effects of reducing negative thinking by the use of affirmations and thought-stopping techniques on women 's mental health Youth in underserved , urban communities are at risk for a range of negative outcomes related to stress , including social-emotional difficulties , behavior problems , and poor academic performance . Mindfulness-based approaches may improve adjustment among chronically stressed and disadvantaged youth by enhancing self-regulatory capacities . This paper reports findings from a pilot r and omized controlled trial assessing the feasibility , acceptability , and preliminary outcomes of a school-based mindfulness and yoga intervention . Four urban public schools were r and omized to an intervention or wait-list control condition ( n = 97 fourth and fifth grade rs , 60.8 % female ) . It was hypothesized that the 12-week intervention would reduce involuntary stress responses and improve mental health outcomes and social adjustment . Stress responses , depressive symptoms , and peer relations were assessed at baseline and post-intervention . Findings suggest the intervention was attractive to students , teachers , and school administrators and that it had a positive impact on problematic responses to stress including rumination , intrusive thoughts , and emotional arousal A large proportion of children experience sub clinical levels of anxiety and cognitive-behavioral therapy ( CBT ) aim ed at preventing anxiety disorders is moderately effective . However , most at-risk children do not seek help or drop out of programs prematurely because of stigma , lack of motivation , and accessibility barriers . Applied games have received increased attention as viable alternatives and have shown promising results , but direct comparisons between applied games and the gold-st and ard CBT are lacking . Our aim was to investigate whether the applied game MindLight is as effective as CBT ( i.e. , Coping Cat ) within an indicated prevention context . We conducted a r and omized controlled non-inferiority trial with a sample of 174 children ( 7- to 12-year olds ) with elevated levels of anxiety , comparing MindLight to CBT . Anxiety was assessed with self- and parent-reports at pre- and post-program , and at 3- and 6-month follow-ups . Intention-to-treat and completers-only confidence interval approach and latent growth curve modeling showed an overall significant quadratic decrease in child- and parent-reported anxiety symptoms over time and , as predicted , the magnitude of improvement was the same for MindLight and CBT . The within-group effect sizes were small to medium at post-test ( − 0.32 to − 0.63 ) , and medium to large ( − 0.60 to − 1.07 ) at 3- and 6-month follow-ups . Furthermore , MindLight and CBT were rated equally anxiety inducing , difficult , and appealing ; CBT was rated as more relevant to daily life than MindLight . The current study adds to the growing research on applied games for mental health and shows that these games hold potential as alternative delivery models for evidence -based therapeutic techniques This study tested the plausibility of a theoretical model of change for the Penn Resiliency Program ( PRP ) , a cognitive-behavioral ( CB ) depression prevention program for adolescents . Middle school students ( N = 697 ) were r and omized to PRP , an assessment -only control condition ( CON ) , or a placebo-control condition ( PLA ) . Explanatory style and depressive symptoms were evaluated over 24 months of follow-up . Relative to both CON and PLA , there were significant indirect effects of PRP on 12-month levels of depressive symptoms through improvements in explanatory style in two of three participating schools . Within a third school , where PRP was not effective in targeting depressive symptoms ( Gillham et al. in J Consult Clin Psychol 75(1):9–19 , 2007 ) , there was no evidence of group differences in growth in explanatory style or indirect effects . When effective , PRP ’s CB training provides incremental value over non-specific components and there are indirect effects on depressive symptoms through improvements in explanatory style The current study aim ed to examine the efficacy of attention bias modification ( ABM ) training to reduce social anxiety in a community-based sample of adolescents 15 - 18 years . The study used a single-blind , parallel group , r and omized controlled trial design ( Clinical Trials ID : NCT02270671 ) . Participants were screened in second-level schools using a social anxiety question naire . 130 participants scoring ≥24 on the Social Phobia and Anxiety Inventory for Children ( SPAI-C ) were r and omized to the ABM training ( n = 66)/placebo ( n = 64 ) group , 120 of which completed pre- , post- , and 12-week follow-up data collection including threat bias , anxiety , and depression measures . The ABM intervention included 4 weekly training sessions using a dot-probe task design ed to reduce attention bias to threatening stimuli . ABM training did not alter the primary outcomes of attention bias to threat or social anxiety symptoms raising questions about the efficacy of ABM as an intervention for adolescents The efficacy of an enhanced version of the Aussie Optimism Program ( AOP ) was investigated in a cluster r and omized controlled trial . Grade 6 students aged 10–11 years of age ( N = 2288 ) from 63 government primary schools in Perth , Western Australia , participated in the pre , post , and follow-up study . Schools were r and omly assigned to one of three conditions : Aussie Optimism with teacher training , Aussie Optimism with teacher training plus coaching , or a usual care condition that received the regular Western Australian Health Education Curriculum . Students in the Aussie Optimism conditions received 20 , 1-h lessons relating to social and interpersonal skills and optimistic thinking skills over the last 2 years of primary school . Parents in the active conditions received a parent information booklet each year , plus a self-directed program in Grade 7 . Students and parents completed the Extended Strengths and Difficulties Question naire . Students who scored in the clinical range on the Emotional Symptoms Scale were given The Diagnostic Interview for Children and Adolescents IV , to assess suicidal ideation and behavior , and depressive and anxiety disorders . Results indicated that Aussie Optimism with teacher training plus coaching was associated with the best outcomes : a significant increase in student-reported pro-social behavior from pre-test to post-test 1 ( maintained at post-test 2 ) and significantly lower incidence rates from suicidal ideation at post-test 2 and follow-up . No significant intervention effects on anxiety and depressive disorders , and total difficulties were reported . These findings suggest that the AOP with teacher training along with coaching may have the potential to positively impact on suicidality and pro-social behavior in the pre-adolescent years To date , most early intervention programs have been based on emotion regulation strategies that address dysfunctional cognitive appraisal s , problem-solving skills , and rumination . Another emotion regulation strategy , ' acceptance ' training , has largely been overlooked . To examine the efficacy of this strategy , a school-based mental health program combining positive psychology with acceptance and commitment therapy ( Strong Minds ) was evaluated in a r and omized controlled trial with a sample of 267 Year 10 and 11 high-school students in Sydney , Australia . Mixed models for repeated measures examined whether the program led to reductions in symptoms amongst students who commenced the program with high depression , anxiety , and stress scores , and increased wellbeing scores amongst all students . Results demonstrated that compared to controls , participants in the Strong Minds condition with elevated symptom scores ( n=63 ) reported significant reductions in depression ( p=.047 ) , stress ( p=.01 ) , and composite depression/anxiety symptoms ( p=.02 ) with medium to strong effect sizes ( Cohen 's d=0.53 , 0.74 , and 0.57 , respectively ) . Increased wellbeing ( p=.03 ) in the total sample and decreased anxiety scores ( p=.048 ) for students with elevated symptoms were significant for Year 10 students with medium effect sizes ( Cohen 's d=0.43 and 0.54 , respectively ) . This study tentatively suggests that including the emotion regulation strategy of acceptance in early intervention programs may be effective in reducing symptoms and improving wellbeing in high school students . Further research to investigate the generalizability of these findings is warranted OBJECTIVE The Re source ful Adolescent Program ( RAP ) is a universal , school-based intervention that has been found to produce small to medium effects in the reduction of adolescent depressive symptoms . In the present study , we evaluated the effectiveness of a friendship-building skills program -- the Peer Interpersonal Relatedness ( PIR ) program -- in producing larger effects when used in conjunction with RAP . METHOD A cluster-r and omized controlled trial was used to assign whole classrooms of adolescent participants recruited from Sydney secondary schools to 1 of 3 conditions : ( a ) RAP-PIR , ( b ) RAP-placebo , or ( c ) assessment -only waiting-list control . Hierarchical linear modeling ( HLM ) was used to analyze the data . RESULTS Across the intervention period , RAP did not significantly reduce depressive symptoms relative to those students not receiving this intervention . RAP followed by PIR did significantly reduce depressive symptoms relative to those students not receiving PIR . Across the 12-month follow-up , the between-group reductions in depressive symptoms were no longer significant . At follow-up , participants in the RAP-PIR condition had achieved significant increases in their school-related life satisfaction and significant increases in social functioning with peers relative to their peers in the other conditions . CONCLUSION The study provides preliminary support for the effectiveness of the PIR program in reducing depressive symptoms when used alongside RAP in the short term and in improving social adjustment and school-related life satisfaction in the longer term . Given the importance of social adjustment in adolescent mental well-being , the PIR program represents a potentially important addition to the prevention of depression in youth BACKGROUND In situations of ongoing violence , childhood psychosocial and mental health problems require care . However , re sources and evidence for adequate interventions are scarce for children in low- and middle-income countries . This study evaluated a school-based psychosocial intervention in conflict-affected , rural Nepal . METHODS A cluster r and omized controlled trial was used to evaluate changes on a range of indicators , including psychiatric symptoms ( depression , anxiety , posttraumatic stress disorder ) , psychological difficulties , resilience indicators ( hope , prosocial behavior ) and function impairment . Children ( n = 325 ) ( mean age = 12.7 , SD = 1.04 , range 11 - 14 years ) with elevated psychosocial distress were allocated to a treatment or waitlist group . RESULTS Comparisons of crude change scores showed significant between-group differences on several outcome indicators , with moderate effect sizes ( Cohen d = .41 to .58 ) . After correcting for nested variance within schools , no evidence for treatment effects was found on any outcome variable . Additional analyses showed gender effects for treatment on prosocial behavior ( mean change difference : 2.70 ; 95 % CI , .97 to 4.44 ) , psychological difficulties ( -2.19 ; 95 % CI , -3.82 to -.56 ) , and aggression ( -4.42 ; 95 % CI , -6.16 to -2.67 ) . An age effect for treatment was found for hope ( .90 ; 95 % CI , -1.54 to -.26 ) . CONCLUSIONS A school-based psychosocial intervention demonstrated moderate short-term beneficial effects for improving social-behavioral and resilience indicators among subgroups of children exposed to armed conflict . The intervention reduced psychological difficulties and aggression among boys , increased prosocial behavior among girls , and increased hope for older children . The intervention did not result in reduction of psychiatric symptoms A controlled trial was conducted to evaluate a prevention program aim ed at reducing depressive and anxious symptoms in rural school children . Seventh- grade children with elevated depression were selected . Nine primary schools ( n = 90 ) were r and omly assigned to receive the program , and 9 control schools ( n = 99 ) received their usual health education classes . Children completed question naires on depression , anxiety , explanatory style , and social skills . Parents completed the Child Behavior Checklist ( T. M. Achenbach , 1991 ) . No intervention effects were found for depression . Intervention group children reported less anxiety than the control group after the program and at 6-month follow-up and more optimistic explanations at postintervention . Intervention group parents reported fewer child internalizing and externalizing symptoms at postintervention only A cluster , stratified r and omized design was used to evaluate the impact of universal , indicated , and combined universal plus indicated cognitive- behavioral approaches to the prevention of depression among 13- to 15-year-olds initially reporting elevated symptoms of depression . None of the intervention approaches differed significantly from a no-intervention condition or from each other on changes in depressive symptoms , anxiety , externalizing problems , coping skills , and social adjustment . All high-symptom students , irrespective of condition , showed a significant decline in depressive symptoms and improvement in emotional well-being over time although they still demonstrated elevated levels of psychopathology compared with the general population of peers at 12-month follow-up . There were also no significant intervention effects for the universal intervention in comparison with no intervention for the total sample of students in those conditions This article reports the results of a study evaluating a book-supported primary prevention program “ Dominique ’s H and y Tricks ” for anxiety disorders in children aged 9–12 years . This cognitive-behavioural program is delivered using a combination of storybooks and workshop sessions . The originality of the program comes from the use of storybooks that were not developed specifically for anxiety management . Every session is based on a story describing characters facing common stressors and how they manage to cope with their daily problems . In our r and omized control trial with 46 children , participation in the program led to a significant improvement in coping skills , perceived self-efficacy , anxiety sensitivity , as well as in symptoms of anxiety and fear . The theoretical and practical elements underlying the delivery of this primary prevention program are described . Conclusion : It is suggested that such an approach , without any labelling specific to anxiety disorders , can be useful in primary prevention programs OBJECTIVE To conduct a placebo-controlled study of the effectiveness of a universal school-based depression prevention program . METHOD Three hundred ninety-two students age 13 to 15 from two schools were r and omized to intervention ( RAP-Kiwi ) and placebo programs run by teachers . RAP-Kiwi was an 11-session manual-based program derived from cognitive-behavioral therapy . The placebo was similar but with cognitive components removed . Outcomes were self-rated depression scales , the Reynolds Adolescent Depression Scale ( RADS ) , and the Beck Depression Inventory II ( BDI-II ) . Follow-up was to 18 months . Analysis was done on an intent-to-treat basis . RESULTS Immediately after the intervention , depression scores were reduced significantly more by RAP-Kiwi than by placebo , with a mean difference in change from baseline between groups of 1.5 on BDI-II ( CI > 0.38 , p = .01 ) and 2.24 on RADS ( CI > 0.22 , p = .04 ) . Categorical analysis confirmed significant clinical benefit with an absolute risk reduction of 3 % ( 95 % CI , 1 - 11 % , McNemar chi , p = .03 ) , with the " number needed to treat " for short-term benefit of 33 . Group differences in depression scores averaged across time to 18 months were significant on RADS but not on BDI-II . Retention rates were 91 % at 6 months and 72 % at 18 months . CONCLUSIONS The RAP-Kiwi program is a potentially effective public health measure . Confirmation of effectiveness measuring episodes of depressive illness and broader measures of adjustment is warranted PROBLEM Incidence of depressive symptoms and lack of sufficient adaptive coping skills in adolescents . METHODS A r and omized controlled study to test the effectiveness of a group-administered , cognitive-behavioral interventions method , TKC , on rural adolescents ( N = 89 ) . Outcomes were measured by changes in the scores on an Adolescent Depression Scale and the Coping Response Inventory pre/post intervention , at 6 and at 12 months . FINDINGS Results indicated improvement in depressive symptomatology and certain coping skills . Students in the intervention reported a higher use of cognitive problem-solving coping strategies . CONCLUSIONS The role of a psychiatric nurse in the school system providing short-term psychoeducation interventions is a practical and effective mental health practice This r and omized controlled trial examined the longitudinal effects of two school-based indicated depression prevention programs on adolescents ’ internalizing and externalizing symptoms , as measured by adolescents , their parents , and their teachers . One hundred eighty-six adolescents participated in this study . The average age was 14.01 ( SD = 1.22 ) years , and the sample was 66.7 % female . One third of the sample belonged to a racial minority . Youth received either Interpersonal Psychotherapy – Adolescent Skills Training or group counseling . Symptoms were assessed using adolescent , parent , and teacher reports on the Achenbach System of Empirically Based Assessment at baseline , postintervention , and 6-month follow-up . Adolescents reported the most robust effects in favor of Interpersonal Psychotherapy – Adolescent Skills Training . Adolescents in Interpersonal Psychotherapy – Adolescent Skills Training reported significantly greater reductions in internalizing symptoms through the 6-month follow-up and significantly greater reductions in externalizing symptoms during the intervention as compared to group counseling . Less robust effects were found when examining parent and teacher reports , although there was evidence of significant within-group change in parent- and teacher-reported internalizing symptoms for both interventions and significant between-group differences in teacher-reported externalizing symptoms . This study provides additional evidence supporting the efficacy of Interpersonal Psychotherapy – Adolescent Skills Training as a depression prevention program for adolescents . Interpersonal Psychotherapy – Adolescent Skills Training appears to have fast-acting effects on broadb and internalizing and externalizing symptoms as reported by adolescents . This suggests that Interpersonal Psychotherapy – Adolescent Skills Training may serve as a transdiagnostic preventive intervention . Moreover , given the disparate reports of adolescents , parents , and teachers , this study demonstrates the significance of collecting information from multiple sources when possible BACKGROUND Anxiety constitutes the most common form of psychopathology in childhood and adolescence . METHODS This r and omised controlled study evaluated the ' FRIENDS for Life ' school-based Cognitive Behavioural Therapy programme on overall anxiety , anxiety subtypes and school adjustment . Sixty-two students aged 12 - 13 completed measures of anxiety and school adjustment before , immediately after and 4 months after completing the programme . Parents and teachers also rated the students on overall anxiety levels and school adjustment respectively . RESULTS The intervention group 's ' overall anxiety ' and specifically ' separation anxiety ' reduced significantly during the programme and continued to decrease at the 4-month follow-up . CONCLUSIONS A significant negative correlation was found between anxiety and school adjustment . The professional implication s of these findings are discussed Adolescent depression is a common and recurrent disorder associated with significant impairment and other forms of psychopathology . Finding an effective intervention that prevents depression in adolescents is an important public health priority . Participants were 518 high school students ( mean age = 15.09 ; SD = 0.76 ) from the mid-south of the United States . Participants were r and omly assigned to 1 of 3 conditions : a cognitive-behavioral program ( CB ; n = 166 ) , nonspecific control ( NSp ; n = 175 ) , or a no-intervention control condition ( NIC ; n = 177 ) . Both the CB and NSp conditions consisted of 90-min sessions administered once a week over a 10-week period during regular school hours . Depressive symptoms were assessed with the Children 's Depression Inventory ( CDI ) at baseline ; postintervention ; and at 4- , 8- , and 12-month follow-ups . The Time × Condition interaction was significant , F(8 , 478.57 ) = 3.32 , p = .001 , indicating that at the 4-month follow-up , youth in the CB condition had significantly lower CDI scores compared with those in the NSp ( p = .047 , g = 0.29 ; CI [ 0.06 , 0.52 ] ) and the NIC conditions ( p = .003 , g = 0.30 ; CI [ 0.07 , 0.53 ] ) . Future studies need to examine the importance of theory-driven change mechanisms , interpersonal relationships , and structural circumstances in schools as factors impacting the long-term effects of CB prevention programs The present research examined the effectiveness of a cognitive-behavioral therapy ( CBT ) based intervention program , FRIENDS , for children from grade s 4 to 6 , using r and om assignment at the school-level and an attention-control design in two longitudinal studies . The first study targeted children with anxiety symptoms ( N=191 , mean age=10.1 ) as screened with self , parent , and teacher-reports ; the second study took a universal approach with full classrooms of children participating ( N=253 , mean age=9.8 ) . The results showed no intervention effect in both studies , with children 's anxiety symptoms decreasing over time regardless of whether they were in the story-reading ( attention control ) or FRIENDS condition . The findings also indicated that girls reported a higher level of anxiety than boys and children in higher grade s reported lower anxiety relative to younger children in both studies . In addition , similar patterns were found using a subgroup of children with high-anxiety symptoms from both studies Given the rise in depression disorders in adolescence , it is important to develop and study depression prevention programs for this age group . The current study examined the efficacy of Interpersonal Psychotherapy-Adolescent Skills Training ( IPT-AST ) , a group prevention program for adolescent depression , in comparison to group programs that are typically delivered in school setting s. In this indicated prevention trial , 186 adolescents with elevated depression symptoms were r and omized to receive IPT-AST delivered by research staff or group counseling ( GC ) delivered by school counselors . Hierarchical linear modeling examined differences in rates of change in depressive symptoms and overall functioning from baseline to the 6-month follow-up assessment . Cox regression compared rates of depression diagnoses . Adolescents in IPT-AST showed significantly greater improvements in self-reported depressive symptoms and evaluator-rated overall functioning than GC adolescents from baseline to the 6-month follow-up . However , there were no significant differences between the two conditions in onset of depression diagnoses . Although both intervention conditions demonstrated significant improvements in depressive symptoms and overall functioning , results indicate that IPT-AST has modest benefits over groups run by school counselors which were matched on frequency and duration of sessions . In particular , IPT-AST outperformed GC in reduction of depressive symptoms and improvements in overall functioning . These findings point to the clinical utility of this depression prevention program , at least in the short-term . Additional follow-up is needed to determine the long-term effects of IPT-AST , relative to GC , particularly in preventing depression onset The authors investigated the effectiveness and specificity of the Penn Resiliency Program ( PRP ; J. E. Gillham , L. H. Jaycox , K. J. Reivich , M. E. P. Seligman , & T. Silver , 1990 ) , a cognitive-behavioral depression prevention program . Children ( N = 697 ) from 3 middle schools were r and omly assigned to PRP , Control ( CON ) , or the Penn Enhancement Program ( PEP ; K. J. Reivich , 1996 ; A. J. Shatté , 1997 ) , an alternate intervention that controls for nonspecific intervention ingredients . Children 's depressive symptoms were assessed through 3 years of follow-up . There was no intervention effect on average levels of depressive symptoms in the full sample . Findings varied by school . In 2 schools , PRP significantly reduced depressive symptoms across the follow-up relative to both CON and PEP . In the 3rd school , PRP did not prevent depressive symptoms . The authors discuss the findings in relation to previous research on PRP and the dissemination of prevention programs BACKGROUND Most adults with common mental disorders report their first symptoms before 24 years of age . Although adolescent anxiety and depression are frequent , little clarity exists about which syndromes persist into adulthood or resolve before then . In this report , we aim to describe the patterns and predictors of persistence into adulthood . METHODS We recruited a stratified , r and om sample of 1943 adolescents from 44 secondary schools across the state of Victoria , Australia . Between August , 1992 , and January , 2008 , we assessed common mental disorder at five points in adolescence and three in young adulthood , commencing at a mean age of 15.5 years and ending at a mean age of 29.1 years . Adolescent disorders were defined on the Revised Clinical Interview Schedule ( CIS-R ) at five adolescent measurement points , with a primary cutoff score of 12 or higher representing a level at which a family doctor would be concerned . Secondary analyses addressed more severe disorders at a cutoff of 18 or higher . FINDINGS 236 of 821 ( 29 % ; 95 % CI 25 - 32 ) male participants and 498 of 929 ( 54 % ; 51 - 57 ) female participants reported high symptoms on the CIS-R ( ≥12 ) at least once during adolescence . Almost 60 % ( 434/734 ) went on to report a further episode as a young adult . However , for adolescents with one episode of less than 6 months duration , just over half had no further common mental health disorder as a young adult . Longer duration of mental health disorders in adolescence was the strongest predictor of clear-cut young adult disorder ( odds ratio [ OR ] for persistent young adult disorder vs none 3.16 , 95 % CI 1.86 - 5.37 ) . Girls ( 2.12 , 1.29 - 3.48 ) and adolescents with a background of parental separation or divorce ( 1.62 , 1.03 - 2.53 ) also had a greater likelihood of having ongoing disorder into young adulthood than did those without such a background . Rates of adolescent onset disorder dropped sharply by the late 20s ( 0.57 , 0.45 - 0.73 ) , suggesting a further resolution for many patients whose symptoms had persisted into the early 20s . INTERPRETATION Episodes of adolescent mental disorder often precede mental disorders in young adults . However , many such disorders , especially when brief in duration , are limited to the teenage years , with further symptom remission common in the late 20s . The resolution of many adolescent disorders gives reason for optimism that interventions that shorten the duration of episodes could prevent much morbidity later in life . FUNDING Australia 's National Health and Medical Research Council Anxiety disorders are prevalent in the school-aged population and are present across cultural groups . Scant research exists on culturally relevant prevention and intervention programs for mental health problems in the Aboriginal population s. An established cognitive behavioral program , FRIENDS for Life , was enriched to include content that was culturally relevant to Aboriginal students . Students ( N = 533 ) , including 192 students of Aboriginal background , participated in the cluster r and omized control study . Data were collected three times over 1 year . A series of multilevel models were conducted to examine the effect of the culturally enriched FRIENDS program on anxiety . These analyses revealed that the FRIENDS program did not effectively reduce anxiety for the total sample or for Aboriginal children specifically . However , all students , regardless of intervention condition , Aboriginal status , or gender , reported a consistent decrease in feelings of anxiety over the 6-month study period Despite the importance of adolescent depression , few school-based prevention programs have been developed and tested in the United States with middle school population s. This study examined the acceptability and changes in targeted outcomes for a new preventative program , Positive Thoughts and Actions ( PTA ) . Sixty-seven 7th grade students with elevated depressive symptoms were recruited from public schools and r and omized to the 12-week PTA program with a parent-component or to a school-as-usual control group . The PTA prevention program was well received by students and parents , yielding high rates of participation and satisfaction among those r and omized to receive the intervention . However , analyses of the efficacy of the program in changing depressive symptoms were not significant . In terms of our proximal program targets , most differences were not statistically significant , though effect sizes suggested advantage of PTA over control group in coping , cognitive style , and parent-child communication . This preliminary research highlights a need for further testing of programs for school-based prevention of depression and promotion of positive emotional health Background Adolescent mental health is characterized by relatively high rates of psychiatric disorders and low levels of help-seeking behaviors . Existing mental health programs aim ed at addressing these issues in adolescents have repeated inconsistent results . Such programs have generally been based on techniques derived from cognitive behavioral therapy , which may not be ideally suited to early intervention among adolescent sample s. Positive psychology , which seeks to improve well-being rather than alleviate psychological symptoms , offers an alternative approach . A previous community study of adolescents found that informal engagement in an online positive psychology program for up to 6 weeks yielded significant improvements in both well-being and depression symptoms . However , this approach had not been trialed among adolescents in a structured format and within a school setting . Objective This study examines the feasibility of an online school-based positive psychology program delivered in a structured format over a 6-week period utilizing a workbook to guide students through website content and interactive exercises . Methods Students from four high schools were r and omly allocated by classroom to either the positive psychology condition , " Bite Back " , or the control condition . The Bite Back condition consisted of positive psychology exercises and information , while the control condition used a series of non-psychology entertainment websites . Both interventions were delivered online for 6 hours over a period of 4 - 6 weeks during class time . Symptom measures and measures of well-being/flourishing and life satisfaction were administered at baseline and post intervention . Results Data were analyzed using multilevel linear modeling . Both conditions demonstrated reductions in depression , stress , and total symptom scores without any significant differences between the two conditions . Both the Bite Back and control conditions also demonstrated significant improvements in life satisfaction scores post intervention . However , only the control condition demonstrated significant increases in flourishing scores post intervention . Conclusions Results suggest that a structured online positive psychology program administered within the school curriculum was not effective when compared to the control condition . The limitations of online program delivery in school setting s including logistic considerations are also relevant to the contradictory findings of this study . Trial Registration Australian New Zeal and Clinical Trials Registry : ACTRN1261200057831 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?id=362489 ( Archived by Webcite at http://www.webcitation.org/6NXmjwfAy ) Regular physical activity is associated with a reduced risk of all-cause mortality , and mortality due to cardiovascular disease and cancer . Among adolescents , physical activity is associated with benefits in the prevention and control of emotional distress , and improvement of self-esteem . Countries in transitional epidemiological scenarios , such as Chile , need to develop effective strategies to improve physical activity as a way to face the epidemic of chronic diseases . The objective of this study was to evaluate the effects of a school-based physical activity program on physical fitness and mental health status of adolescents living in a low socioeconomic status area in Santiago , Chile . A quasi-experimental design was used to evaluate the effects of the program over one academic year . The study included 198 students aged 15 years old . Two ninth grade classes were r and omly selected as the intervention group , with two classes of the same grade as controls . A social planning approach was used to develop the intervention . The program was design ed and implemented based on student preferences , teachers ' expertise and local re sources . Changes in physiological and mental health status were assessed . After the intervention , maximum oxygen capacity achieved a significant increase of 8.5 % in the intervention versus 1.8 % in the control group ( p < 0.0001 ) . Speed and jump performance scores improved significantly more in the intervention versus the control group ( p > 0.01 ) . Anxiety score decreased 13.7 % in the intervention group versus 2.8 % in the control group ( p < 0.01 ) , and self-esteem score increased 2.3 % in the intervention group and decreased 0.1 % in the control group after the end of the program ( p < 0.0001 ) . No significant change was observed in the depressive score . Student participation and compliance with the program was > 80 % . To conclude , a school-based program to improve physical activity in adolescents of low socioeconomic status , obtained a high level of participation and achieved significant benefits in terms of physical fitness and mental health status In this depression prevention trial , 341 high-risk adolescents ( mean age = 15.6 years , SD = 1.2 ) with elevated depressive symptoms were r and omized to a brief group cognitive-behavioral ( CB ) intervention , group supportive-expressive intervention , bibliotherapy , or assessment -only control condition . CB participants showed significantly greater reductions in depressive symptoms than did supportive-expressive , bibliotherapy , and assessment -only participants at posttest , though only the difference compared with assessment controls was significant at 6-month follow-up . CB participants showed significantly greater improvements in social adjustment and reductions in substance use at posttest and 6-month follow-up than did participants in all 3 other conditions . Supportive-expressive and bibliotherapy participants showed greater reductions in depressive symptoms than did assessment -only controls at certain follow-up assessment s but produced no effects for social adjustment and substance use . CB , supportive-expressive , and bibliotherapy participants showed a significantly lower risk for major depression onset over the 6-month follow-up than did assessment -only controls . The evidence that this brief CB intervention reduced risk for future depression onset and outperformed alternative interventions for certain ecologically important outcomes suggests that this intervention may have clinical utility Anxiety and depression are the most commonly reported mental health problems amongst Australian children and adolescents . The Aussie Optimism : Program-Positive Thinking Skills ( AOP-PTS ) is a universal intervention program based on cognitive and behavioral strategies and aim ed to prevent anxiety and depression in the middle primary school children aged 9–10 years old . 370 students r and omly assigned to the intervention and control condition participated in the 42 and 54 months follow-up study . The intervention group received the AOP-PTS 10-week program and the control group received the regular health education curriculum . Students were assessed on anxiety , depression and attribution style at school whilst parents reported on their child ’s externalizing and internalizing problems at home . Results showed there were no significant reductions across groups in the depressive and anxiety symptoms , and attribution style at either 42 or 54 months follow-up . These findings suggest that AOP-PTS has short and medium term effects but were not sustained in longer term period . Future strategies to achieve the desirable outcomes in a longitudinal study are discussed The Aussie Optimism Program : Feelings and Friends ( AOP-FF ) is a 10 week , universal mental health promotion program based on social/emotional and cognitive and behavioral strategies . The aim of the current study was to evaluate the efficacy of a universal Cognitive Behavioral Therapy based program in preventing and reducing internalizing problems in 6–8 year olds ( Years 1–3 in Australia ) . Year 1–3 students from a low SES primary school ( N = 206 ) were r and omly assigned in classes to either an intervention or a control group and assessed at baseline and post-test . Results showed a significant ( p = 0.009 ) and small to moderate ( partial eta-squared = 0.034 ) pre-post decrease in parent-reported anxiety symptoms for the intervention group , in conjunction with a non-significant ( p = 0.708 ) and negligible ( partial eta-squared = 0.001 ) pre-post increase for the control group . A larger r and omized controlled trial assessing longer term effects is needed . In addition the program needs to be simplified for year 1–2 students with a separate more developmentally appropriate program for year 3 students We investigated factors hypothesized to moderate the effects of cognitive behavioral group-based ( CB group ) and bibliotherapy depression prevention programs . Using data from two trials ( N = 631 ) wherein adolescents ( M age = 15.5 , 62 % female , 61 % Caucasian ) with depressive symptoms were r and omized into CB group , CB bibliotherapy , or an educational brochure control condition , we evaluated the moderating effects of individual , demographic , and environmental factors on depressive symptom reductions and major depressive disorder ( MDD ) onset over 2-year follow-up . CB group and bibliotherapy participants had lower depressive symptoms than controls at posttest but these effects did not persist . No MDD prevention effects were present in the merged data . Relative to controls , elevated depressive symptoms and motivation to reduce depression amplified posttest depressive symptom reduction for CB group , and elevated baseline symptoms amplified posttest symptom reduction effects of CB bibliotherapy . Conversely , elevated substance use mitigated the effectiveness of CB group relative to controls on MDD onset over follow-up . Findings suggest that both CB prevention programs are more beneficial for youth with at least moderate depressive symptoms , and that CB group is more effective for youth motivated to reduce their symptoms . Results also imply that substance use reduces the effectiveness of CB group-based depression prevention Background Depression is a disabling condition affecting people of all ages , but generally starting during adolescence . Schools seem to be an excellent setting where preventive interventions may be delivered . This study aim ed to test the effectiveness of an indicated school-based intervention to reduce depressive symptoms among at-risk adolescents from low-income families . Methods A two-arm , parallel , r and omized controlled trial was conducted in 11 secondary schools in vulnerable socioeconomic areas in Santiago , Chile . High-risk students in year 10 ( 2 ° Medio ) were invited to a baseline assessment ( n = 1048 ) . Those who scored ≥10 ( boys ) and ≥15 ( girls ) in the BDI-II were invited to the trial ( n = 376 ) . A total of 342 students consented and were r and omly allocated into an intervention or a control arm in a ratio of 2:1 . The intervention consisted of 8 group sessions of 45 min each , based on cognitive-behavioural models and delivered by two trained psychologists in the schools . Primary ( BDI-II ) and secondary outcomes ( measures of anxiety , automatic thoughts and problem-solving skills ) were administered before and at 3 months post intervention . The primary outcome was the recovery rate , defined as the proportion of participants who scored in the BDI-II < 10 ( among boys ) and < 15 ( among girls ) at 3 months after completing the intervention . Results There were 229 participants in the intervention group and 113 in the control group . At 3-month follow-up 81.4 % in the intervention and 81.7 % in the control group provided outcome data . The recovery rate was 10 % higher in the intervention ( 50.3 % ) than in the control ( 40.2 % ) group ; with an adjusted OR = 1.62 ( 95 % CI : 0.95 to 2.77 ) ( p = 0.08 ) . No difference between groups was found in any of the secondary outcomes . Secondary analyses revealed an interaction between group and baseline BDI-II score . Conclusions We found no clear evidence of the effectiveness of a brief , indicated school-based intervention based on cognitive-behavioural models on reducing depressive symptoms among Chilean adolescents from low-income families . More research is needed in order to find better solutions to prevent depression among adolescents . Trial registration Current Controlled Trials IS RCT N33871591 . Retrospectively registered 29 June 2011 Although cognitive-behavioural programmes for preventing depression have produced promising findings , their administration requires extensive training . Relaxation techniques are more straightforward psychological strategies , but they have not been investigated in the prevention of depression . This trial aim ed to compare the results of relaxation training ( RT ) with that of a cognitive-behavioural programme ( CBT ) for prevention of depression in university students with elevated depressive symptoms . The 133 participants ( mean age 23.3 years , 82 % women ) were r and omly assigned to CBT or RT . Both programmes were administered to groups of 5 or 6 participants in eight weekly 90-min sessions . Participants were evaluated by independent raters before , immediately after , and 3 and 6 months after taking part in the programmes . By itself , intervention type had no significant effect on either depression or anxiety scores . The scores were lower at the follow-up time points with respect to pre-intervention scores . Effect size was greatest between pre- and immediately post-intervention scores for CBT , d = 1.32 , 95 % CI [ 1.00 , 1.64 ] , and between pre- and 6-month post-intervention scores for RT , d = 0.75 , 95 % CI [ 0.47 , 1.03 ] . Anxiety symptoms were significantly improved by both interventions at 3-month follow-up , and by CBT at 6-month follow-up also . In the medium term ( 3 - 6 months ) , relaxation training produced similar reductions in depressive and anxiety symptoms as a more complex cognitive-behavioural programme Childhood anxiety is a problem not only because of its negative consequences on the well-being of children but also because of its adverse effects on society and its role in mental disorders later in life . Adequate prevention might be the key in tackling this problem . The effectiveness of Coping Cat , as an indicated CBT-based prevention program in Dutch primary school children , was assessed by means of a r and omized controlled trial . In total , 141 children aged 7–13 with elevated levels of anxiety and their mothers were included and r and omly assigned to an intervention group and a waiting list control group . After screening , all participants completed baseline , post-intervention , and 3-month follow-up assessment s. The results showed that Coping Cat , as an indicated prevention program , reduces children ’s self-reported anxiety symptoms , with Cohen ’s effect size d of 0.66 at the 3-month follow-up . A moderating effect was found for baseline anxiety level ; specifically , children with high levels of baseline anxiety who received the Coping Cat program had lower anxiety levels at follow-up compared to children with high levels of anxiety in the control condition . No moderating effects of gender or age were found . An unexpected decline in anxiety levels from screening to pre- assessment was found in both groups , and this decline was stronger in the experimental group . These promising results warrant the implementation of Coping Cat as an indicated prevention program Social anxiety is a common mental disorder among adolescents and is associated with detrimental long term outcomes . Therefore , this study investigated the efficacy of two possible early interventions for adolescent social anxiety and test anxiety . An internet-based cognitive bias modification ( CBM ; n = 86 ) was compared to a school-based cognitive behavioral group training ( CBT ; n = 84 ) and a control group ( n = 70 ) in reducing symptoms of social and test anxiety in high socially and /or test anxious adolescents aged 13–15 years . Participants ( n = 240 ) were r and omized at school level over the three conditions . CBM consisted of a 20-session at home internet-delivered training ; CBT was a 10-session at school group training with homework assignments ; the control group received no training . Participants were assessed before and after the intervention and at 6 and 12 month follow-up . At 6 month follow-up CBT result ed in lower social anxiety than the control condition , while for CBM , this effect was only trend-significant . At 12 month follow-up this initial benefit was no longer present . Test anxiety decreased more in the CBT condition relative to the control condition in both short and long term . Interestingly , in the long term , participants in the CBM condition improved more with regard to automatic threat-related associations than both other conditions . The results indicate that the interventions result ed in a faster decline of social anxiety symptoms , whereas the eventual end point of social anxiety was not affected . Test anxiety was influenced in the long term by the CBT intervention , and CBM lead to increased positive automatic threat-related associations . Trial Registration TrialRegister.nl Major depression and dysthymia are frequent , debilitating , and chronic disorders , whose highest rate of initial onset is during the late adolescent years . The effectiveness of a program design ed to prevent an initial episode of major depression or dysthymia among adolescents was investigated . Participants were 171 fourteen-year-old " at risk " Icel and ic adolescents who were r and omly assigned to a prevention program or a treatment-as-usual assessment only control group . They were identified as " at risk " by reporting the presence of depressive symptoms or a negative attributional style . The program was based on a developmental psychosocial model of enhancement of resilience to factors associated with the occurrence of mood disorders . The results indicated that the prevention program result ed in a significantly lower rate of major depression and dysthymia than did the control group . The study demonstrated that school personnel in the school setting can implement such prevention programs This study evaluated the effectiveness of rational-emotive therapy and rational-emotive imagery . Fifty-nine junior high school students who volunteered to participate in treatment for interpersonal anxiety were r and omly assigned to rational-emotive therapy without imagery ( RET ) , rational-emotive therapy with imagery ( REI ) , relationship-oriented counseling ( ROC ) , and waiting-list control ( WLC ) groups . Groups met for seven 50-minute treatment sessions during a three-week period . Assessment s were conducted at pretreatment , posttreatment , and three-week follow-up . Both self-report and sociometric measures were used to evaluate treatment outcome . At post assessment , both the RET and REI groups were rated on sociometric measures as significantly less interpersonally anxious than the WLC group . Mean scores favored the RET and REI groups , but no significant differences between these groups and the ROC group were obtained . The self-report measure did not significantly differentiate between groups , but the REI group demonstrated significant pre- to follow-up changes . Both the RET and REI groups yielded greater reductions in irrational thinking than did the ROC and WLC groups . In addition , the pattern of the results supported the use of rational-emotive imagery as a component of rational-emotive therapy . The practical implication s of these findings are discussed This paper describes the development and preliminary efficacy of a program design ed to prevent depressive symptoms in at-risk 10 - 13 year-olds , and relates the findings to the current underst and ing of childhood depression . The treatment targets depressive symptoms and related difficulties such as conduct problems , low academic achievement , low social competence , and poor peer relations , by proactively teaching cognitive techniques . Children were identified as ' at-risk ' based on depressive symptoms and their reports of parental conflict . Sixty-nine children participated in treatment groups and were compared to 73 children in control groups . Depressive symptoms were significantly reduced and classroom behavior was significantly improved in the treatment group as compared to controls at post-test . Six-month follow-up showed continued reduction in depressive symptoms , as well as significantly fewer externalizing conduct problems , as compared to controls . The reduction in symptoms was most pronounced in the children who were most at risk The effects of teacher-directed cognitive self-instruction ( TI ) were compared with an instructions-only component control condition ( IO ) in order to examine the former 's efficacy as a primary prevention strategy . In a quasi-experimental design . two intact high school psychology classes were r and omly assigned to either TI or IO . Each condition lasted for eight 45-minute class periods , and each group was given an in vivo homework assignment . Pretreatment equivalence and dem and analyses yielded no evidence of differences . Results of a posttreatment measure of attitude toward treatments and a pre- and posttreatment measure of state anxiety suggested that trainerdirected cognitive self-instruction may be a promising primary prevention strategy Limited research has indicated the effectiveness of the school-based Cognitive Behavioral Therapy ( CBT ) prevention program ' Op Volle Kracht ( OVK ) ' and the computerized CBT program ' SPARX ' in decreasing depressive symptoms . Therefore , a r and omized controlled trial of the effectiveness of OVK and SPARX was conducted among Dutch female adolescents ( n = 208 , mean age = 13.35 ) with elevated depressive symptoms . Participants were r and omly assigned to one of four conditions : OVK only ( n = 50 ) , SPARX only ( n = 51 ) , OVK and SPARX combined ( n = 56 ) and a monitoring control condition ( n = 51 ) . Participants in the first three conditions received OVK lessons and /or the SPARX game . Depressive symptoms were assessed before interventions started , weekly during the interventions , and immediately after the interventions ended , with follow-up assessment s at 3 , 6 and 12 months . Intention to treat results showed that depressive symptoms decreased in all conditions ( F(12 , 1853.03 ) = 14.62 , p < .001 ) , with no difference in depressive symptoms between conditions . Thus , all conditions , including the monitoring control condition , were equally effective in reducing depressive symptoms . Possible explanations for the decrease of depressive symptoms in all conditions are discussed and suggestions for future research are provided . Dutch Trial Register : NTR3737 This study was conducted to compare the outcomes of a group-based cognitive-behavioral preventive intervention ( Positive Thoughts and Actions [ PTA ] ) tailored to youth in middle school with a brief , individually administered supportive intervention ( Individual Support Program [ ISP ] ) . A r and omized , controlled trial was conducted with 120 early adolescents ( 72 girls , 48 boys ; age = 11–15 years ) who had elevated depressive symptoms and were selected from a school-based population . Measures of internalizing problems , externalizing problems , personal adjustment , school problems , and interpersonal relations were obtained from parents , youth , and /or teachers at preintervention ( Time 1 ) and postintervention ( Time 2 , 5–7 months after preintervention ) . General linear model repeated measures analyses yielded a significant Group × Time interaction on youth-reported , but not parent-reported , depressive symptoms and internalizing symptoms . Youth in the PTA group showed greater decreases following intervention compared to youth who received ISP , yielding effect sizes ( Cohen 's d ) of 0.36 for depressive symptoms , 95 % CI [ –.02 , .73 ] , and 0.44 , 95 % CI [ .05 , .82 ] , for internalizing symptoms . PTA youth also showed improvements in their personal adjustment ( sense of inadequacy , self-esteem ) , and parent-reported social skills , but no differences emerged between groups for externalizing symptoms , school problems , or interpersonal relationships . Cognitive-behavioral preventive interventions in which youth engage in personal goal - setting and practice social-emotional skills , such as PTA , may be beneficial for the reduction of depressive symptoms over and above general support and empathy Abstract Anxiety sensitivity ( AS ) is recognized as an early risk factor for the development of anxiety disorders . This study evaluates whether a brief school-based selective prevention program reduces AS and anxious and depressive symptoms in children and youth . Participants scoring high in AS but without any current psychopathological disorder were selected from a sample of 613 individuals ( 61 % female , 11–17 years old ) and r and omly assigned to the prevention program ( n=47 ) or to a waiting-list control ( WLC ) ( n=45 ) group . A normal control ( NC ) group ( n=53 ) was also included . After treatment , a significant decrease in AS and in anxiety and depressive symptoms were observed in both prevention and WLC groups . Differences between experimental conditions only emerged , partially , at six-month follow-up ( FU ) with the prevention group ( PG ) exhibiting significantly lower AS ( p<.05 ) , and equalling NCs . Although the magnitude of change in the PG is comparable to that reported in previous studies with longer and more complex prevention programs , a parallel reduction in the WLCs suggests that the observed decrease in the short term could be mostly time-linked . Despite this , our results encourage research into brief preventive interventions at an individual level The goal of this study was to evaluate potential mental health benefits of yoga for adolescents in secondary school . Students were r and omly assigned to either regular physical education classes or to 11 weeks of yoga sessions based upon the Yoga Ed program over a single semester . Students completed baseline and end-program self-report measures of mood , anxiety , perceived stress , resilience , and other mental health variables . Independent evaluation of individual outcome measures revealed that yoga participants showed statistically significant differences over time relative to controls on measures of anger control and fatigue/inertia . Most outcome measures exhibited a pattern of worsening in the control group over time , whereas changes in the yoga group over time were either minimal or showed slight improvements . These preliminary results suggest that implementation of yoga is acceptable and feasible in a secondary school setting and has the potential of playing a protective or preventive role in maintaining mental health BACKGROUND Yoga programs geared for school children have become more widespread , but research regarding its impact on children is lacking . Several studies have reported positive outcomes , though there is a need for more r and omised controlled trials . OBJECTIVES To determine the effects of yoga on children 's emotional and behavioural functioning when compared with physical education ( PE ) classes . METHODS Thirty middle school children were r and omised to participate in either a school-based Ashtanga-informed yoga or PE class three times a week for 12 weeks . Emotional ( i.e. affect , self-perceptions ) and behavioural ( i.e. internalising and externalising problems , aggression ) functioning were measured pre and post-intervention . RESULTS There were no significant changes between groups in self-reported positive affect , global self-worth , aggression indices or parent reports of their children 's externalising and internalising problems . However , negative affect increased for those children participating in yoga when compared to the PE program . CONCLUSIONS In general , findings suggest that yoga and PE classes do not differentially impact on middle school children 's emotional and behavioural functioning . However , children reported experiencing increased negative emotions after receiving yoga while children in the PE group reported a decrease in these feelings . Implication s of these results and potential directions for future research on children 's yoga are discussed OBJECTIVE Depressive disorders in adolescents are a widespread problem with extensive psychosocial consequences . The authors design ed a school-based program to prevent the increase in depressive symptoms . The authors expect the program to reduce dysfunctional automatic thoughts and improve social skills and thus prevent the increase in depressive symptoms . METHOD The design includes a training group and a nontreatment control group with pre- and post-measurement and 3- and 6-month follow-up . The authors followed up 324 eighth grade rs in both groups . School classes were r and omly assigned to one of the two groups . The prevention program , LISA-T , is based on cognitive-behavioral therapy concepts and targets of cognitive and social aspects . It comprises 10 meetings of 1.5 hours in a regular school setting . RESULTS Increases in depressive symptoms in nondepressed adolescents in the training group were prevented over a 6-month period . Furthermore , adolescents with subsyndromal depression in the training group reported fewer symptoms , whereas depressive symptoms within the control group did not change . However , the groups did not differ with regard to social skills , frequency of negative automatic thoughts , and depressive symptoms before the prevention program . CONCLUSIONS LISA-T is an effective school-based prevention program for eighth grade rs with minimal to mild depressive symptoms , but further research is needed Anxiety , depression and eating disorders show peak emergence during adolescence and share common risk factors . School-based prevention programs provide a unique opportunity to access a broad spectrum of the population during a key developmental window , but to date , no program targets all three conditions concurrently . Mindfulness has shown promising early results across each of these psychopathologies in a small number of controlled trials in schools , and therefore this study investigated its use in a r and omised controlled design targeting anxiety , depression and eating disorder risk factors together for the first time . Students ( M age 13.63 ; SD = .43 ) from a broad b and of socioeconomic demographics received the eight lesson , once weekly.b ( " Dot be " ) mindfulness in schools curriculum ( N = 132 ) or normal lessons ( N = 176 ) . Anxiety , depression , weight/shape concerns and wellbeing were the primary outcome factors . Although acceptability measures were high , no significant improvements were found on any outcome at post-intervention or 3-month follow-up . Adjusted mean differences between groups at post-intervention were .03 ( 95 % CI : -.06 to -.11 ) for depression , .01 ( -.07 to -.09 ) for anxiety , .02 ( -.05 to -.08 ) for weight/shape concerns , and .06 ( -.08 to -.21 ) for wellbeing . Anxiety was higher in the mindfulness than the control group at follow-up for males , and those of both genders with low baseline levels of weight/shape concerns or depression . Factors that may be important to address for effective dissemination of mindfulness-based interventions in schools are discussed . Further research is required to identify active ingredients and optimal dose in mindfulness-based interventions in school setting BACKGROUND The study evaluated the efficacy of an indicated prevention program for adolescent depression . METHODS Fifty-seven adolescents with elevated depression symptoms were r and omized to receive Interpersonal Psychotherapy-Adolescent Skills Training ( IPT-AST ) or school counseling ( SC ) . Hierarchical linear modeling examined differences in rates of change in depression symptoms and overall functioning and analysis of covariance examined mean differences between groups . Rates of depression diagnoses in the 18-month follow-up period were compared . RESULTS Adolescents in IPT-AST reported significantly greater rates of change in depression symptoms and overall functioning than SC adolescents from baseline to post-intervention . At post-intervention , IPT-AST adolescents reported significantly fewer depression symptoms and better overall functioning . During the follow-up phase , rates of change slowed for the IPT-AST adolescents , whereas the SC adolescents continued to show improvements . By 12-month follow-up , there were no significant mean differences in depression symptoms or overall functioning between the two groups . IPT-AST adolescents reported significantly fewer depression diagnoses in the first 6 months following the intervention but by 12-month follow-up the difference in rates of diagnoses was no longer significant . CONCLUSIONS IPT-AST leads to an immediate reduction in depression symptoms and improvement in overall functioning . However , the benefits of IPT-AST are not consistent beyond the 6-month follow-up , suggesting that the preventive effects of the program in its current format are limited . Future studies are needed to examine whether booster sessions lengthen the long-term effects of IPT-AST BACKGROUND Indicated interventions for adolescents with elevated depressive symptoms may help decrease rates of depression . The current study reports on the efficacy of Interpersonal Psychotherapy-Adolescent Skills Training ( IPT-AST ) , a group indicated preventive intervention . METHODS Forty-one adolescents with elevated depression symptoms were r and omized to receive either IPT-AST or school counseling ( SC ) as delivered by guidance counselors and social workers . Adolescents in the two intervention conditions were compared on depression symptoms , overall functioning , and depression diagnoses post-intervention and at 3-month and 6-month follow-up . RESULTS Adolescents who received IPT-AST had significantly fewer depression symptoms and better overall functioning post-intervention and at follow-up . Adolescents in IPT-AST also reported fewer depression diagnoses than adolescents in usual care . CONCLUSIONS These results provide preliminary evidence of the efficacy of IPT-AST as an intervention for adolescents with subthreshold depression . Future research is needed to confirm the efficacy of IPT-AST in a larger and more diverse sample and to determine its long-term impact on depression symptoms and depression diagnoses A r and omised controlled trial evaluated the Aussie Optimism Program in preventing anxiety and depression . Grade 7 students ( n = 496 ) from disadvantaged government schools in Perth Western Australia , participated . Six schools were r and omly assigned to Aussie Optimism and six schools received their usual health education lessons . Students completed question naires on depression , anxiety , attribution style , and social skills . Parents completed the Child Behavior Checklist . No significant group effects were found for student-reported data . Parents of intervention group only students reported reductions in internalizing problems at post-test . No follow-up group effects were significant . Students and teachers found the program acceptable This trial compared a brief group cognitive-behavioral ( CBT ) depression prevention program to a waitlist control condition and four placebo or alternative interventions . High-risk adolescents with elevated depressive symptoms ( N=225 , M age=18 , 70 % female ) were r and omized to CBT , supportive-expressive group intervention , bibliotherapy , expressive writing , journaling , or waitlist conditions and completed assessment s at baseline , termination , and 1- and 6-month follow-up . All five active interventions showed significantly greater reductions in depressive symptoms at termination than waitlist controls ; effects for CBT and bibliotherapy persisted into follow-up . CBT , supportive-expressive , and bibliotherapy participants also showed significantly greater decreases in depressive symptoms than expressive writing and journaling participants at certain follow-up points . Findings suggest there may be multiple ways to reduce depressive symptoms in high-risk adolescents , although expectancies , dem and characteristics , and attention may have contributed to the observed effects OBJECTIVES This investigation attempted to prevent unipolar depressive episodes in a sample of high school adolescents with an elevated risk of depressive disorder . METHOD Adolescents at risk for future depressive disorder by virtue of having elevated depressive symptomatology were selected with a two-stage case-finding procedure . The Center for Epidemiologic Studies -Depression Scale ( CES-D ) was administered to 1,652 students ; adolescents with elevated CES-D scores were interviewed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children . Subjects with current affective diagnoses were referred to nonexperimental services . The remaining 150 consenting subjects were considered at risk for future depression and r and omized to either a 15-session cognitive group prevention intervention or an " usual care " control condition . Subjects were reassessed for DSM-III-R diagnostic status after the intervention and at 6- and 12-month follow-up points . RESULTS Survival analyses indicated a significant 12-month advantage for the prevention program , with affective disorder total incidence rates of 14.5 % for the active intervention , versus 25.7 % for the control condition . No differences were detected for nonaffective disorders across the study period . CONCLUSION Depressive disorder can be successfully prevented among adolescents with an elevated future risk The authors tested whether a brief indicated cognitive-behavioral depression prevention program produced similar effects for Asian American , Latino , and European American adolescents ( M age = 17.3 , SD = 1.6 ) with elevated depressive symptoms using data from two r and omized trials . The first trial involved 37 Asian-American/Pacific Isl and ers , 32 Latinos , and 98 European Americans and the second trial involved 61 Latinos and 72 European Americans . Reductions in depressive symptoms from pre- to post-intervention and from pre to 6-month follow-up for intervention participants versus assessment -only controls did not differ significantly for the various ethnic groups in either trial , despite sufficient power to detect clinical ly meaningful differences . These findings suggest that this indicated depression prevention intervention is similarly efficacious for Asian American , Latino and European American adolescents Objective : To assess the effectiveness of an indicated early intervention and prevention programme for anxiety disorders when conducted by school staff . Method : A total of 260 students in their first year of high school with self-reported anxiety symptoms > 1 SD above the mean score of a normative sample were r and omly allocated on the basis of their school to an intervention condition led by school staff or to a monitoring condition . Results : There was little difference between conditions at the 2 year and 4 year follow up on self-reported symptoms , and no difference on diagnosis or health-care use . Conclusions : Outcomes associated with indicated prevention programmes led by school staff may not be as strong as those produced by specialist mental health staff . More work is needed to delineate models by which evidence -based treatments can be effectively used in schools BACKGROUND This r and omized controlled trial evaluated the efficacy of a preventive intervention for anxiety disorders and depression by targeting excessive levels of repetitive negative thinking ( RNT ; worry and rumination ) in adolescents and young adults . METHODS Participants ( N = 251 , 83.7 % female ) showing elevated levels of RNT were r and omly allocated to a 6-week cognitive-behavioral training delivered in a group , via the internet , or to a waitlist control condition . Self-report measures were collected at pre-intervention , post-intervention , 3 m and 12 m follow-up . RESULTS Both versions of the preventive intervention significantly reduced RNT ( d = 0.53 to 0.89 ) , and symptom levels of anxiety and depression ( d = 0.36 to 0.72 ) . Effects were maintained until 12 m follow-up . The interventions result ed in a significantly lower 12 m prevalence rate of depression ( group intervention : 15.3 % , internet intervention : 14.7 % ) and generalized anxiety disorder ( group intervention : 18.0 % , internet intervention : 16.0 % ) , compared to the waitlist ( 32.4 % and 42.2 % , respectively ) . Mediation analyses demonstrated that reductions in RNT mediated the effect of the interventions on the prevalence of depression and generalized anxiety disorder . CONCLUSIONS Results provide evidence for the efficacy of this preventive intervention targeting RNT and support a selective prevention approach that specifically targets a known risk factor to prevent multiple disorders This article reports results from a universal preventive program aim ed at ( a ) reducing social anxiety and ( b ) preventing the development of syndromal social anxiety among a population -based sample of older children and young adolescents during a 1-year period . Pupils ( N = 1,748 ) from 2 counties were cluster r and omized to either an intervention or a control condition . In the intervention condition , the Norwegian Universal Preventive Program for Social Anxiety (NUPP-SA)-which educates pupils , parents/guardians , teachers/school staff , and county health workers-was administered . The results indicate that NUPP-SA had a significant specific intervention effect for reducing social anxiety in the total sample as well as among the syndromal subjects . Further , significantly fewer subjects from the intervention county developed syndromal social anxiety during the 1-year period , thus showing a prevention effect . The results demonstrate the value of an intervention specifically aim ed at reducing social anxiety and preventing the development of syndromal social anxiety among young people OBJECTIVE We tested whether a brief cognitive behavioral ( CB ) group and bibliotherapy prevention reduce major depressive disorder ( MDD ) onset , depressive symptoms , and secondary outcomes relative to brochure controls in adolescents with self-reported depressive symptoms when school personnel recruit participants and deliver the intervention . METHOD Three hundred seventy-eight adolescents ( M age = 15.5 years , SD = 1.2 ; 68 % female , 72 % White ) with elevated self-assessed depressive symptoms were r and omized to a 6-session CB group , minimal contact CB bibliotherapy , or educational brochure control . Participants were assessed at pretest , posttest , and 6-month follow-up . RESULTS CB group participants showed a significantly lower risk for major depressive disorder onset ( 0.8 % ) , compared to both CB bibliotherapy ( 6.3 % ) and brochure control ( 6.5 % ; hazard ratio = 8.1 and 8.3 , respectively ) . Planned contrasts indicated that CB group result ed in lower depressive symptom severity than brochure control at posttest ( p = .03 , d = 0.29 ) but not 6-month follow-up ; differences between CB group and bibliotherapy were nonsignificant at posttest and 6-month follow-up . Condition effects were nonsignificant for social adjustment and substance use . CONCLUSIONS The finding that a brief CB group intervention delivered by real-world providers significantly reduced MDD onset relative to both brochure control and bibliotherapy is very encouraging , although effects on continuous outcome measures were small or nonsignificant and approximately half the magnitude of those found in efficacy research , potentially because the present sample reported lower initial depression This study examined the effects of meridian exercise on anxiety , depression , and self-esteem of female college students in Korea . The effects of meridian exercise on anxiety , depression , and self-esteem were statistically significant ( t = -7.982 , P= .000 ; t= -8.814 , P = .000 ; t = 9.649 , P = .000 ) between the experimental and control group BACKGROUND Depressive disorders are experienced by 3 - 5 % of the adolescent population at any point of time . They adversely affect adolescent development in a range of areas and greatly increase risk for suicide . The present study investigated the effectiveness of a universal intervention design ed to reduce depressive symptoms among students commencing high school . METHODS Twenty-five pairs of secondary schools matched on socio-economic status were r and omly assigned to either an intervention or a comparison group ( n = 5,634 Year 8 students ) . The intervention extended over a 3-year period and utilised a comprehensive classroom curriculum programme , enhancements to the school climate , improvements in care pathways , and community forums . A range of measures completed by students , average age at baseline = 13.1 years ( SD = .5 ) , and teachers was used to assess changes in depressive symptoms , risk and protective factors relevant to depression , and the quality of the school environment . RESULTS Changes in the level of depressive symptoms and in the levels of risk and protective factors experienced by students in the two groups did not differ significantly over the 3 years of the study . Furthermore , statistically significant differences in the ratings of school climate across this time period were found only for staff-rated assessment s. CONCLUSIONS Despite using an extensive , structured programme , based on best evidence to increase protective factors and reduce risk factors at the individual and school levels , the intervention did not reduce levels of depressive symptoms among participating adolescents . The results draw attention to the difficulties faced when implementing large-scale , school-based , universal preventive interventions . These include the need to develop methods to effectively train teachers across large geographical regions to deliver new interventions with fidelity , the difficulty of engaging young adolescents with prevention programmes , and the long period of time required to implement policy and practice changes at ' whole-school ' levels This study evaluated the efficacy of 2 programs for preventing depressive symptoms in adolescents . Participants were 380 high school students r and omly assigned to a cognitive-behavioral program ( CB ) , an interpersonal psychotherapy-adolescent skills training program ( IPT-AST ) , or a no-intervention control . The interventions involved eight 90-min weekly sessions run in small groups during wellness classes . At postintervention , students in both the CB and IPT-AST groups reported significantly lower levels of depressive symptoms than did those in the no-intervention group , controlling for baseline depression scores ; the 2 intervention groups did not differ significantly from each other . The effect sizes , using Cohen 's d , for the CB intervention and the IPT-AST intervention were 0.37 and 0.26 , respectively . Differences between control and intervention groups were largest for adolescents with high levels of depressive symptoms at baseline . For a high-risk subgroup , defined as having scored in the top 25th percentile on the baseline depression measure , the effect sizes for the CB and the IPT-AST interventions were 0.89 and 0.84 , respectively . For the whole sample , sociotropy and achievement orientation moderated the effect of the interventions . Intervention effects were short term and were not maintained at 6-month follow-up To prevent depression and anxiety , we delivered a brief , classroom-based cognitive-behavioral workshop along with ongoing Web-based material s and e-mail coaching to college students at risk for depression . At risk was defined as having mild to moderate depressive symptoms on a self-report measure of depression . Two hundred forty students were r and omized into either an eight-week workshop that met in groups of 10 , once per week for 2 h or into an assessment -only control group . We plan to track participants for 3 years after the workshop and here we report the 6 month preventive effects on depression and anxiety . The workshop group had significantly fewer depressive symptoms and anxiety symptoms than the control group , but there was no significant difference between the conditions on depression or anxiety episodes at 6 month follow up . The workshop group had significantly better well being than the control group , and the workshop group had significantly greater improvement in optimistic explanatory style than the control group . Improved explanatory style was a significant mediator of the prevention effects from pre- to post-workshop for depressive and anxiety symptoms , as well as for improved well being PURPOSE This study tested the efficacy of an intervention for anxious adolescent boys experiencing bullying at school . The cognitive-behavioral intervention focused on targeting individual factors that appear to increase an adolescent 's vulnerability to bullying experiences such as anxiety , low self-esteem , and use of maladaptive coping strategies . METHODS Adolescent boys reporting anxiety symptoms and the recent experience of being bullied at school ( grade s 7 - 10 ) were r and omly assigned by group to intervention ( n = 22 ) or wait-list ( n = 24 ) conditions . Depressive and anxiety symptoms and bullying experiences were measured before and after the intervention , and at a 3-month follow-up for the intervention condition . RESULTS The intervention was effective in significantly reducing adolescent 's bullying experiences as well as their anxiety , depression , and the degree of distress associated with being bullied . Intervention gains were maintained at the 3-month follow-up . The intervention was not effective in enhancing adolescent 's self-esteem or changing aggressive or avoidant responses to bullying situations . CONCLUSIONS This study provides preliminary support for the value of individually focused interventions for boys in the effort to reduce the incidence of bullying within schools IMPORTANCE Depression can have devastating effects unless prevented or treated early and effectively . Schools offer an excellent opportunity to intervene with adolescents presenting emotional problems . There are very few universal school-based depression interventions conducted in low- and middle-income countries . OBJECTIVE To assess the effectiveness of a school-based , universal psychological intervention to reduce depressive symptoms among adolescents from low-income families . DESIGN , SETTING , AND PARTICIPANTS A 2-arm , parallel , cluster , r and omized clinical trial was conducted in secondary schools in deprived socioeconomic areas of Santiago , Chile . Almost all students registered in the selected schools consented to take part in the study . A total of 2512 secondary school students from 22 schools and 66 classes participated . INTERVENTIONS Students in the intervention arm attended 11 one-hour weekly and 2 booster classroom sessions of an intervention based on cognitive-behavioral models . The intervention was delivered by trained nonspecialists . Schools in the control arm received the st and ard school curriculum . MAIN OUTCOMES AND MEASURES Scores on the self-administered Beck Depression Inventory-II at 3 months ( primary ) and 12 months ( secondary ) after completing the intervention . RESULTS There were 1291 participants in the control arm and 1221 in the intervention arm . Primary outcome data were available for 82.1 % of the participants . There was no evidence of any clinical ly important difference in mean depression scores between the groups ( adjusted difference in mean , -0.19 ; 95 % CI , -1.22 to 0.84 ) or for any of the other outcomes 3 months after completion of the intervention . No significant differences were found in any of the outcomes at 12 months . CONCLUSIONS AND RELEVANCE A well- design ed and implemented school-based intervention did not reduce depressive symptoms among socioeconomically deprived adolescents in Santiago , Chile . There is growing evidence that universal school interventions may not be sufficiently effective to reduce or prevent depressive symptoms . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N19466209 This study evaluated the efficacy of a school-based anxiety prevention program among urban children exposed to community violence . Students who attended Title 1 public elementary schools were screened . Ninety-eight 3rd–5th- grade students ( ages 8–12 ; 48 % female ; 92 % African American ) were r and omized into preventive intervention versus waitlist comparison groups . Students attended 13 biweekly one-hour group sessions of a modified version of FRIENDS , a cognitive-behavioral anxiety intervention program . Results indicated that both intervention and control groups manifested significant reductions in anxiety symptomatology and total exposure to community violence , along with improved st and ardized reading achievement scores . Additional gains observed only in the intervention group were increased st and ardized mathematics achievement scores , decreased life stressors , and reduced victimization by community violence . The intervention was equally efficacious for both genders and for children exposed to higher , compared to lower , levels of community violence . Implication s for comprehensive , culturally and context ually relevant prevention programs and research are discussed Preliminary data are presented on the effectiveness of a universal school-based intervention for the prevention of anxiety symptoms in primary school children . A sample of 489 children ( aged 10 - 12 years ) were assigned to one of three intervention conditions : a psychologist-led preventive intervention , a teacher-led preventive intervention , or a usual care ( st and ard curriculum ) with monitoring condition . The intervention offered was the Friends for Children programme , a 12-session cognitive-behavioural intervention , originally based upon Kendall 's ( 1994 ) Coping Cat programme . Participants in both intervention conditions reported fewer symptoms of anxiety at post-intervention than participants in the usual care condition . These preliminary results suggest that universal programmes for childhood anxiety are promising intervention strategies that can be successfully delivered to a school-based population and integrated into the classroom curriculum Depression among Mexican immigrant women and children exceeds national prevalence rates . Given the influence of maternal depression on children , a clinical trial testing the effects of the Mexican American Problem Solving ( MAPS ) program was design ed to address depression symptoms of Mexican immigrant women and their fourth and fifth grade children ( 302 dyads ) through a linked home visiting and after school program compared to peers in a control group . Schools were r and omized to intervention and control groups . There were statistically significant improvements in the children 's health conceptions and family problem solving communication , factors predictive of mental health . Improvements in children 's depression symptoms in the intervention group approached statistical significance . These promising results suggest that refined school based nursing interventions be included in community strategies to address the serious mental health problems that Mexican immigrants face Given the dramatic increase in depression that occurs during early adolescence in girls , interventions must address the needs of girls . The authors examined whether a depression prevention program , the Penn Resiliency Program , was more effective for girls in all-girls groups than in co-ed groups . Within co-ed groups , the authors also tested whether there were greater effects for boys than for girls . Participants were 20811-to 14-year-olds . Girls were r and omly assigned to all-girls groups , co-ed groups , or control . Boys were assigned to co-ed groups or control . Students completed question naires on depressive symptoms , hopelessness , and explanatory style before and after the intervention . Girls groups were better than co-ed groups in reducing girls ’ hopelessness and for session attendance rates but were similar to co-ed groups in reducing depressive symptoms . Co-ed groups decreased depressive symptoms , but this did not differ by gender . Findings support prevention programs and suggest additional benefits of girls groups BACKGROUND Depression in adolescents is a significant problem that impairs everyday functioning and increases the risk of severe mental health disorders in adulthood . Although this is a major problem , relatively few adolescents with , or at risk of developing , depression are identified and referred for treatment . This suggests the need to investigate alternative approaches whereby preventative interventions are made widely available in schools . OBJECTIVE To investigate the clinical effectiveness and cost-effectiveness of classroom-based cognitive-behavioural therapy ( CBT ) in reducing symptoms of depression in high-risk adolescents . DESIGN Cluster r and omised controlled trial . Year groups ( n = 28 ) r and omly allocated on a 1 : 1 : 1 basis to one of three trial arms once all schools were recruited and balanced for number of classes , number of students , Personal , Social and Health Education ( PSHE ) lesson frequency , and scheduling of PSHE . SETTING Year groups 8 to 11 ( ages 12 - 16 years ) in mixed-sex secondary schools in the UK . Data were collected between 2009 and 2011 . PARTICIPANTS Young people who attended PSHE at participating schools were eligible ( n = 5503 ) . Of the 5030 who agreed to participate , 1064 ( 21.2 % ) were classified as ' high risk ' : 392 in the classroom-based CBT arm , 374 in the attention control PSHE arm and 298 in the usual PSHE arm . Primary outcome data on the high-risk group at 12 months were available for classroom-based CBT ( n = 296 ) , attention control PSHE ( n = 308 ) and usual PSHE ( n = 242 ) . INTERVENTIONS The Re source ful Adolescent Programme ( RAP ) is a focused CBT-based intervention adapted for the UK ( RAP-UK ) and delivered by two facilitators external to the school . Control groups were usual PSHE ( usual school curriculum delivered by teachers ) and attention control ( usual school PSHE with additional support from two facilitators ) . Interventions were delivered universally to whole classes . PRIMARY OUTCOMES Clinical effectiveness : symptoms of depression [ Short Mood and Feelings Question naire ( SMFQ ) ] in adolescents at high risk of depression 12 months from baseline . Cost-effectiveness : incremental cost-effectiveness ratios ( ICERs ) based on SMFQ score and quality -adjusted life-years ( from European Quality of Life-5 Dimensions scores ) between baseline and 12 months . Process evaluation : reach , attrition and qualitative feedback from service recipients and providers . RESULTS SMFQ scores had decreased for high-risk adolescents in all trial arms at 12 months , but there was no difference between arms [ classroom-based CBT vs. usual PSHE adjusted difference in means 0.97 , 95 % confidence interval ( CI ) -0.34 to 2.28 ; classroom-based CBT vs. attention control PSHE -0.63 , 95 % CI -1.99 to 0.73 ] . Costs of interventions per child were estimated at £ 41.96 for classroom-based CBT and £ 34.45 for attention control PSHE . Fieller 's method was used to obtain a parametric estimate of the 95 % CI for the ICERs and construct the cost-effectiveness acceptability curve , confirming that classroom-based CBT was not cost-effective relative to the controls . Reach of classroom-based CBT was good and attrition was low ( median 80 % attending ≥ 60 % of sessions ) , but feedback indicated some difficulties with acceptability and sustainability . CONCLUSIONS Classroom-based CBT , attention control PSHE and usual PSHE produced similar outcomes . Classroom-based CBT may result in increased self-awareness and reporting of depressive symptoms . Classroom-based CBT was not shown to be cost-effective . While schools are a convenient way of reaching a wide range of young people , implementing classroom-based CBT within schools is challenging , particularly with regard to fitting programmes into a busy timetable , the lack of value placed on PSHE , and difficulties engaging with teachers and young people . Wider use of classroom-based depression prevention programmes should not be undertaken without further research . If universal preventative approaches are to be pursued , their clinical effectiveness and cost-effectiveness with younger children ( aged 10 - 11 years ) , before the incidence of depression increases , should be investigated . Alternatively , the clinical effectiveness of indicated school-based programmes targeting those already displaying symptoms of depression should be investigated . TRIAL REGISTRATION Current Controlled Trials IS RCT N19083628 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 17 , No. 47 . See the HTA programme website for further project information The aim in the current study was to investigate the effectiveness of an online , self-directed cognitive-behavioral therapy program ( MoodGYM ) in preventing and reducing the symptoms of anxiety and depression in an adolescent school-based population . A cluster r and omized controlled trial was conducted with 30 schools ( N = 1,477 ) from across Australia , with each school r and omly allocated to the intervention or wait-list control condition . At postintervention and 6-month follow-up , participants in the intervention condition had significantly lower levels of anxiety than did participants in the wait-list control condition ( Cohen 's d = 0.15 - 0.25 ) . The effects of the MoodGYM program on depressive symptoms were less strong , with only male participants in the intervention condition exhibiting significant reductions in depressive symptoms at postintervention and 6-month follow-up ( Cohen 's d = 0.27 - 0.43 ) . Although small to moderate , the effects obtained in the current study provide support for the utility of universal prevention programs in schools . The effectiveness of booster sessions should be explored in future research AIMS Suppose you are the developer of a new therapy for a mental health problem or you have several years of experience working with such a therapy , and you would like to prove that it is effective . R and omised trials have become the gold st and ard to prove that interventions are effective , and they are used by treatment guidelines and policy makers to decide whether or not to adopt , implement or fund a therapy . METHODS You would want to do such a r and omised trial to get your therapy disseminated , but in reality your clinical experience already showed you that the therapy works . How could you do a trial in order to optimise the chance of finding a positive effect ? RESULTS Methods that can help include a strong allegiance towards the therapy , anything that increases expectations and hope in participants , making use of the weak spots of r and omised trials ( risk of bias ) , small sample sizes and waiting list control groups ( but not comparisons with existing interventions ) . And if all that fails one can always not publish the outcomes and wait for positive trials . CONCLUSIONS Several methods are available to help you show that your therapy is effective , even when it is not OBJECTIVE Mindfulness is being promoted in schools as a prevention program despite a current small evidence base . The aim of this research was to conduct a rigorous evaluation of the .b ( " Dot be " ) mindfulness curriculum , with or without parental involvement , compared to a control condition . METHOD In a r and omized controlled design , students ( Mage 13.44 , SD 0.33 ; 45.4 % female ) across a broad range of socioeconomic indicators received the nine lesson curriculum delivered by an external facilitator with ( N = 191 ) or without ( N = 186 ) parental involvement , or were allocated to a usual curriculum control group ( N = 178 ) . Self-report outcome measures were anxiety , depression , weight/shape concerns , wellbeing and mindfulness . RESULTS There were no differences in outcomes between any of the three groups at post-intervention , six or twelve month follow-up . Between-group effect sizes ( Cohen 's d ) across the variables ranged from 0.002 to 0.37 . A wide range of moderators were examined but none impacted outcome . CONCLUSIONS Further research is required to identify the optimal age , content and length of mindfulness programs for adolescents in universal prevention setting s. TRIAL REGISTRATION ACTRN12615001052527 The aim of this pilot study was to evaluate the acceptability and feasibility of delivering an online anxiety prevention program in schools , and to assess the effectiveness of the intervention in reducing symptoms of anxiety . Three schools located in South Australia and the Australian Capital Territory were recruited to participate in the trial , with classes r and omly allocated to the intervention or wait-list control condition . All participants ( N = 225 ) were invited to complete a pre-intervention , post-intervention and 3-month follow-up question naire . Participants in the intervention condition completed the online e-couch Anxiety and Worry program during one class period a week for six weeks . No significant differences were found between the intervention and control conditions at post-intervention or 3-month follow-up for generalised anxiety ( Cohen 's d = − 0.09–0.08 ) , social anxiety ( d = 0.09 & − 0.26 ) , anxiety sensitivity ( d = 0.19 & − 0.15 ) , depressive symptoms ( d = 0.01 & 0.08 ) or mental wellbeing ( d = 0.17 & 0.30 ) . Online anxiety prevention programs are acceptable and can be feasibly delivered in schools . Although not significant , the sizes of some of the effects obtained in this pilot trial are consistent with earlier studies , and warrant further investigation in a larger trial BACKGROUND This study evaluated the efficacy of a universal prevention program for adolescent depresssion implemented by school teachers in Mauritius . METHOD 160 adolescents were r and omly assigned to the prevention program or wait-list . RESULTS Decreased depressive symptoms for the intervention condition were found post-intervention , but not at follow-up . Significant changes in self-esteem and coping skills were seen both post-intervention and at the follow-up . CONCLUSIONS The results , drawing from a culturally diverse population , suggest that universal programs such as RAP-A may be better seen as promoting positive mental health , rather than having direct prevention or intervention effects on clinical problems BACKGROUND The impact of occupational therapy on mental health outcomes for children is largely unexplored . The aim of this study was to investigate an evidence -based occupational therapy intervention design ed to increase participation in daily occupations to prevent symptoms of mental illness for children and run in schools . METHODS The study used a pragmatic , cluster-r and omised controlled trial design with two arms . Fourteen clusters ( schools ) , equating to 151 child participants , were stratified by school decile-rank category and block r and omised . Blinding of participants post-r and omisation was not feasible ; however , outcomes assessors were blinded . Outcomes were measured at baseline , after the parallel and crossover phases , and at follow-up ; and were anxiety symptoms ( primary ) , depression symptoms , self-esteem , participation and wellbeing . Intention-to-treat analysis was applied and mixed linear modelling was used to account for clusters and repeated measures , and to adjust for covariates identified . RESULTS This trial found significant positive effects of the intervention on child-rated satisfaction with their occupational performance and teacher-rated child anxiety . No evidence was found to support the effect of the intervention on anxiety and depression symptoms , self-esteem and wellbeing . CONCLUSIONS This was the first known cluster-r and omised controlled trial to investigate an occupational therapy intervention promoting emotional wellbeing in a non- clinical sample of children . No compelling evidence was found to support the use of the intervention in schools in its current format , however , results were promising that the focus on occupations influenced participation . Recommendations are made to re design the intervention as an embedded intervention in the classroom , cotaught by teachers and including parental involvement BACKGROUND Anxiety is a common mental health problem in youth . The current study aim ed to test the effectiveness of an online self-directed anxiety prevention program in a school-based sample and to compare two methods of implementing an anxiety program in schools . METHODS A three-arm cluster stratified r and omised controlled trial was conducted with 30 Australian schools . Each school was r and omly assigned to receive : ( 1 ) externally-supported intervention , ( 2 ) teacher-supported intervention , or ( 3 ) wait-list control . All consenting students ( N=1767 ) were invited to complete pre-intervention , post-intervention , 6- and 12-month follow-up question naires measuring generalised anxiety , social anxiety , anxiety sensitivity , depressive symptoms and mental wellbeing . Intervention participants completed the e-couch Anxiety and Worry program over 6 weeks . RESULTS At post-intervention , 6- and 12-month follow-up no significant differences were observed between the intervention and control conditions for generalised anxiety ( Cohen 's d=-0.14 to 0.15 ) , social anxiety ( d=0.04 - 0.23 ) , anxiety sensitivity ( d=-0.07 to 0.07 ) , depressive symptoms ( d=-0.05 to 0.04 ) or mental wellbeing ( d=-0.06 to -0.30 ) . LIMITATIONS The current study only included self-report measures that may have been influenced by situational factors or biases . CONCLUSIONS The e-couch Anxiety and Worry program did not have a significant positive effect on participant mental health or wellbeing . The addition of a mental health education officer to support classroom teachers in the delivery of the program also had no effect on intervention outcomes . Future prevention research should look to develop briefer and more interactive interventions that are more engaging for youth The aim of the present study was to examine the differential effects of strategies for promotion of psychological well-being ( Well-Being Therapy , WBT ) and removal of distress ( Anxiety Management , AM ) in a non- clinical school setting .162 students attending middle schools in Northern Italy were r and omly assigned to : ( a ) a protocol derived from WBT ; ( b ) an anxiety-management protocol ( AM ) . The students were assessed immediately before and after the interventions , and after 6 months using : Psychological Well-Being Scales ( PWB ) , Symptom Question naire ( SQ ) and the Revised Children 's Manifest Anxiety Scale ( RCMAS ) . In school children , well-being and symptom focused interventions produced slightly different effects on psychological dimensions . WBT , by facilitating progression toward positive and optimal functioning , may integrate symptom-centered strategies Depression is a common psychological problem in adolescence . Recent research suggests that group cognitive-behavioral interventions can reduce and prevent symptoms of depression in youth . Few studies have tested the effectiveness of such interventions when delivered by school teachers and counselors ( as opposed to research team staff ) . We evaluated the effectiveness of the Penn Resiliency Program for adolescents ( PRP-A ) , a school-based group intervention that targets cognitive behavioral risk factors for depression . We r and omly assigned 408 middle school students ( ages 10–15 ) to one of three conditions : PRP-A , PRP-AP ( in which adolescents participated in PRP-A and parents were invited to attend a parent intervention component ) , or a school-as-usual control . Adolescents completed measures of depression and anxiety symptoms , cognitive style , and coping at baseline , immediately after the intervention , and at 6-month follow-up . PRP-A reduced depression symptoms relative to the school as usual control . Baseline levels of hopelessness moderated intervention effects . Among participants with average and high levels of hopelessness , PRP ( A and AP ) significantly improved depression symptoms , anxiety symptoms , hopelessness , and active coping relative to control . Among participants with low baseline hopelessness , we found no intervention effects . PRP-AP was not more effective than PRP-A alone . We found no intervention effects on clinical levels of depression or anxiety . These findings suggest that cognitive-behavioral interventions can be beneficial when delivered by school teachers and counselors . These interventions may be most helpful to students with elevated hopelessness The longitudinal effectiveness of a universal , adolescent school-based depression prevention program Op Volle Kracht ( OVK ) was evaluated by means of a cluster r and omized controlled trial with intervention and control condition ( school as usual ) . OVK was based on the Penn Resiliency Program ( PRP ) ( Gillham et al. Psychological Science , 6 , 343–351 , 1995 ) . Depressive symptoms were assessed with the Child Depression Inventory ( Kovacs 2001 ) . In total , 1341 adolescents participated , Mage = 13.91 , SD = 0.55 , 47.3 % girls , 83.1 % Dutch ethnicity ; intervention group n = 655 , four schools ; control group n = 735 , five schools . Intent-to-treat analyses revealed that OVK did not prevent depressive symptoms , β = −0.01 , SE = 0.05 , p = .829 , Cohen ’s d = 0.02 , and the prevalence of an elevated level of depressive symptoms was not different between groups at 1 year follow-up , OR = 1.00 , 95 % CI = 0.60–1.65 , p = .992 , NNT = 188 . Latent Growth Curve Modeling over the 2 year follow-up period showed that OVK did not predict differences in depressive symptoms immediately following intervention , intercept : β = 0.02 , p = .642 , or changes in depressive symptoms , slope : β = −0.01 , p = .919 . No moderation by gender or baseline depressive symptoms was found . To conclude , OVK was not effective in preventing depressive symptoms across the 2 year follow-up . The implication s of these findings are discussed A r and omized controlled trial was conducted among a potential high-risk group of 1,343 adolescents from low-income areas in The Netherl and s to test the effectiveness of the depression prevention program Op Volle Kracht ( OVK ) as provided by teachers in a school setting . The results showed no main effect of the program on depressive symptoms at one-year follow-up . A moderation effect was found for parental psychopathology ; adolescents who had parents with psychopathology and received the OVK program had less depressive symptoms compared to adolescents with parents with psychopathology in the control condition . No moderating effects on depressive symptoms were found for gender , ethnical background , and level of baseline depressive symptoms . An iatrogenic effect of the intervention was found on the secondary outcome of clinical depressive symptoms . Based on the low level of reported depressive symptoms at baseline , it seems that our sample might not meet the characteristics of a high-risk selective group for depressive symptoms . Therefore , no firm conclusions can be drawn about the selective potential of the OVK depression prevention program . In its current form , the OVK program should not be implemented on a large scale in the natural setting for non-high-risk adolescents . Future research should focus on high-risk participants , such as children of parents with psychopathology |
747 | 10,908,512 | There was moderate evidence that for primary prevention lumbar supports are not more effective than other types of treatment or no intervention .
No evidence was found on the effectiveness of lumbar supports for secondary prevention .
The systematic review of therapeutic trials showed that there is limited evidence that lumbar supports are more effective than no treatment , while it is still unclear if lumbar supports are more effective than other interventions for treatment of low back pain . | BACKGROUND Lumbar supports are used in the treatment of low back pain patients to make the impairment and disability vanish or decrease .
Lumbar supports are also used to prevent the onset of low back pain ( primary prevention ) or to prevent recurrences of a low back pain episode ( secondary prevention ) .
OBJECTIVES The objective of this systematic review was to assess the effects of lumbar supports for prevention and treatment of non-specific low back pain . | The recent increased utilization of industrial back belts as personal protective equipment in the workplace has generated considerable controversy among occupational health and safety professionals in the United States . The purpose of this article is to review the literature regarding proposed mechanisms of action of these devices and studies related to outcome of belt utilization in the prevention of low back pain and disability in the workplace . At the present time , neither the suspected mechanisms of action nor the efficacy of these devices in the primary , secondary , and tertiary prevention of work-related low back pain has been adequately demonstrated in clinical trials . As a result , generally accepted guidelines regarding the safe use of belts in the occupational setting have not been established . Based on this review it is recommended that further well-controlled , prospect i ve , r and omized clinical trials are necessary to evaluate the effectiveness of these devices as personal protective equipment . During the interim , the decision to prescribe belts to employees in the workplace should be at the discretion of an adequately trained occupational health care provider . These devices should not be provided as an alternative to appropriate administrative and /or engineering controls Radiographic instability seemingly enjoys the status of a well-defined clinical syndrome . The concept is widely used , and specific treatments , usually spinal fusion , are routinely performed based on the diagnosis . The minimum st and ards necessary to establish radiographic instability as a legitimate clinical syndrome have not been established , however . The primary purpose of this study was to determine if treatment involving bracing , exercise , and education controlling either flexion or extension postures , would result in a distinctive pattern of favorable or unfavorable results , depending on the type of radiographic instability ( retrodisplacement or spondylolisthesis ) . Fifty-six patients meeting strict study inclusion and radiographic evaluation criteria were assigned signed to a bracing treatment ( flexion , extension , placebo-control ) according to a r and omization scheme , design ed to ensure equal representation of translation categories ( retro , normal , spondy ) across treatment groups , and assessed at admission and 1-month follow-up . The sample was relatively evenly divided between men ( 46 % ) and women ( 54 % ) , and by age . Translation classification was related to both gender and age , with men more likely classified as retro and women more likely spondy and patients in their 20s having lower incidence of spondy and higher incidence of normal translation . Translation classification was not related to selected indices of low-back pain history . Brace treatments were not shown to reduce patient range of motion or lessen trunk strength . A significant treatment by time interaction for the modified pain interference ( VAS ) scale indicated improvement for patients in extension compared with patients in flexion and control-placebo treatments . In conjunction with no significant three-way interaction between treatment , translation classification , and time , it was hypothesized that radiographic instability might more appropriately be considered a corroborative sign of advanced discogenic problems . Improvement in extension treatment , regardless of the type of radiographic abnormality , suggests that the treating clinician might consider extension treatment for chronic low-back pain patients . Causes and implication s for the failure of this study to provide support for considering radiographic instability as a clinical syndrome are considered and future directions for this area of research suggested This study was design ed to determine the effect of multimodal intervention and the prevention of back injury , and to evaluate the adverse side effects of using a lumbosacral corset in the workplace . Subjects were 90 male warehouse workers r and omly selected from over 800 employees at a grocery distribution center . Subjects were assigned to three groups : true controls , no back school , no brace orthoses ; back school only ; and back school plus wearing a custom molded lumbosacral orthosis . Comparisons of pre-testing and 6-month follow-up posttesting for abdominal strength , cognitive data , work injury incidence and productivity and use of health care services were evaluated . Controls and training-only group showed no changes in strength productivity or lost time . Orthoses and training-group showed no changes in strength productivity or accident rate ; however , they showed substantially less lost time . This study supports the concept of using education and prophylactic bracing to prevent back injury and reduce time loss . It appears that the use of intermittent prophylactic bracing has no adverse affects on abdominal muscle strength and may contribute to decreased lost time from work injuries Study Design A r and omized prospect i ve trial of manipulation , massage , corset and transcutaneous muscle stimulation ( TMS ) was conducted in patients with subacute low back pain . Objectives The authors determined the relative efficacy of chiropractic treatment to massage , corset , and TMS . Summary of Background Data Although all of these treatments are used for subacute low back pain treatment , there have been few comparative trials using objective outcome criteria . Patients were enrolled for a period of 3 weeks . They were evaluated once a week by question naires , visual analog scale , range of motion , maximum voluntary extension effort , straight leg raising and Biering-Sorensen fatigue test . The dropout rate was highest in the muscle stimulation and corset groups and lowest in the manipulation group . Rates of full compliance did not differ significantly across treatments . A measure of patient confidence was greatest in the manipulation group . Results After 3 weeks , the manipulation group scored the greatest improvements in flexion and pain while the massage group had the best extension effort and fatigue time , and the muscle stimulation group the best extension . Conclusion None of the changes in physical outcome measures ( range of motion , fatigue , strength or pain ) were significantly different between any of the groups A prospect i ve epidemiologic study was conducted in two units ( 140 beds and 57 nursing assistants ) of a nursing home to demonstrate the efficacy of an ergonomic intervention strategy to reduce back stress to nursing personnel . The total programme involved the following : determining patient h and ling tasks perceived to be most stressful by the nursing assistants ( NAs ) ; performing an ergonomic evaluation of these tasks ; and conducting a laboratory study to select patient transferring devices perceived to produce less physical stress than existing manual patient-h and ling methods . The intervention phase included training NAs in the use of these devices , modifying toilets and shower rooms , and applying techniques to patient care . Immediately after completing the intervention programme , a post-intervention analysis ( which lasted eight months in unit 1 and four months in unit 2 ) was performed . A biomechanical evaluation of the physical dem and s required to perform stressful patient-h and ling tasks showed that the mean compressive force on the L5/S1 disc , the mean h and force required to make a transfer , and the strength requirements ( expressed as percentage female population capable ) were 1964 N , 122 N , and 83 % after intervention as compared to 4751 N , 312 N , and 41 % before intervention . Subjectively , the mean rating of perceived exertion was less than ' very light ' after intervention as compared to between ' somewhat hard ' and ' hard ' before intervention . Overall , the mean acceptability rates for the walking belt and the mechanical hoist were 81 % and 87 % for patient transfers . The incidence rate for back injuries prior to the intervention , 83 per 200,000 work-hours , decreased to 47 per 200,000 work-hours after the intervention . There were no injuries result ing in lost or restricted work days during the last four months of the post-intervention . It is concluded that an appropriate ergonomic intervention programme offers great promise in reducing physical stress and risk of low-back pain to nursing personnel . However , large-scale studies in different nursing homes are needed to confirm the above findings |
748 | 25,528,992 | The authors found no cases of symptomatic DVT or PE in either the calf-thigh compression group or the plantar compression group during the first three weeks after the THR .
The calf-thigh pneumatic compression was more effective than plantar compression for reducing thigh swelling during the early postoperative stage .
There is a lack of evidence from r and omized controlled trials to make an informed choice of IPC device for preventing venous thromboembolism ( VTE ) following total hip replacement . | BACKGROUND Total hip replacement ( THR ) is an effective treatment for reducing pain and improving function and quality of life in patients with hip disorders .
While this operation is very successful , deep vein thrombosis ( DVT ) and pulmonary embolism ( PE ) are significant complications after THR .
Different types of intermittent pneumatic compression ( IPC ) devices have been used for thrombosis prophylaxis in patients following THR .
Available devices differ in compression garments , location of air bladders , patterns of pump pressure cycles , compression profiles , cycle length , duration of inflation time and deflation time , or cycling mode such as automatic or constant cycling devices .
Despite the widely accepted use of IPC for the treatment of arterial and venous diseases , the relative effectiveness of different types of IPC systems as prophylaxis against thrombosis after THR is still unclear .
OBJECTIVES To assess the comparative effectiveness and safety of different IPC devices with respect to the prevention of venous thromboembolism in patients after THR . | OBJECTIVE To eluci date the time course and magnitude of hemodynamic and fibrinolytic changes associated with sequential gradient intermittent pneumatic compression ( SGIPC ) . DESIGN Two-phase , intervention and response investigation in normal volunteers . MATERIAL S AND METHODS Subjects were assigned to control ( phase I ) or compression ( phase II ) groups . Serial blood sample s were obtained via femoral venous catheters for tissue plasminogen activator ( tPA ) , plasminogen activator inhibitor ( PAI-1 ) , tPA-PAI-1 complex ( tPA-PAI ) , and euglobulin lysis time ( ELT ) from all subjects and for fibrin degradation products ( FbDP ) and fibrinogen degradation products ( FgDP ) from phase II subjects . Duplex venous scanning was carried out on phase II subjects before and during SGIPC . RESULTS Catheter placement caused elevations in PAI-1 and tPA-PAI , which stabilized within 4 hours of catheter insertion . In phase II , SGIPC induced significant increases in FbDP , FgDP , and tPA-PAI and decreases in ELT and PAI-1 , all of which quickly reverted to baseline on termination of compression . Femoral venous blood flow increased by more than 100 % with SGIPC . CONCLUSIONS Sequential gradient intermittent pneumatic compression induces prompt , but short-lived , alterations in both fibrinolytic and hemodynamic function . Noncontinuous SGIPC may result in suboptimal thromboembolic prophylaxis Introduction This prospect i ve study was design ed to confirm risk factors and to assess the incidence of deep vein thrombosis after total hip and surface replacement arthroplasty in Korean patients not receiving anticoagulation prophylaxis and to determine efficacy of plasma D-dimer levels as a screening test . Material s and methods From May 2003 to August 2004 , 221 consecutive patients undergoing unilateral total hip arthroplasty and hip resurfacing were evaluated . All patients underwent ultrasonography preoperatively and venography and /or ultrasonography on postoperative day 7 . Plasma D-dimer levels were estimated by latex immuno-assay preoperatively and on days 3 and 7 postoperatively . Results Of the 221 patients in our cohort , 23 developed deep vein thrombosis ( 10.4 % ) . Age ( r = 0.245 , P < 0.001 ) and gender ( r = 0.155 , P = 0.021 ) significantly correlated with deep vein thrombosis . Rise in incidence paralleled increase in age ( X2 = 32.860 , P < 0.001 ) . D-dimer levels on postoperative days 3 ( γ = 0.364 , P < 0.001 ) and 7 ( γ = 0.470 , P < 0.001 ) were significantly correlated to the development of DVT . Conclusion While incidence of deep vein thrombosis in Korean population after THA was lower than that in the West ; it increased with age , and in female gender . Significant correlation was found between D-dimer levels and the development of deep vein thrombosis D-dimers may be elevated after surgery . However , the kinetics of postoperative D-dimers remains unknown hampering the use of D-dimer testing in surgical patients with suspected venous thromboembolism . D-dimer levels were prospect ively measured in 154 patients after general surgery at predefined time points ( kinetics were determined in an initial cohort of 108 patients ; for validation , these findings were applied to a second cohort of 46 patients ) . Clinical factors influencing the peak of D-dimers were analyzed using multivariate regression . Surgical operations were stratified based on severity ( type I : not entering abdominal cavity ; type II : intraabdominal ; type III : retroperitoneal/liver surgery ) . D-dimer levels increased postoperatively reaching a peak on day 7 . After type I surgery , peak D-dimer levels did not exceed normal range ( 300 ng/ml , 100–500 ) . After type II procedures , peak D-dimer level was 1500 ng/ml ( 200–7800 ) and returned to normal values after 25 days ( ±14 ) . Peak level was 4000 ng/ml ( 500–14 400 ) after type III surgery normalizing within 38 days ( ±11 ) . Clearance of D-dimer was exponential after having reached the peak with 6.0 % per day ( 95 % confidence interval 4.8–7.1 % ) . By this clearance , D-dimer values could be adequately predicted in the validation cohort after day 7 ( r2 = 0.63 ) . Peak D-dimer levels were independently influenced by the type of surgery ( P < 0.001 ) , the operation time ( P < 0.001 ) and by preoperatively elevated D-dimer levels ( P < 0.001 ) . Based on this data , duration of postoperative D-dimer elevation after abdominal surgery is predictable . This study indicates for the first time when D-dimers may be used again in the diagnostic algorithm for venous thromboembolism exclusion after surgery in patients with low or moderate clinical probability The WizAir-DVT is a miniature , lightweight ( 690 g ) , battery-operated and mobile intermittent pneumatic compression device ( ICD ) , which enables continuous intraoperative use and immediate patient mobilization postoperatively . We compared its efficacy with a commonly used ICD , the Kendall SCD . Peak femoral vein flow velocity was measured in 20 apparently healthy volunteers at rest and with each device : we found no significant differences between them . A second prospect i ve , r and omized , clinical trial was used to compare the efficiency of the device in preventing deep venous thrombosis ( DVT ) after joint replacement in 50 patients ( n=25/group ) . None developed DVT . Doppler ultrasonography revealed no significant differences . The WizAir-DVT antithrombotic compression device is as safe and effective as the Kendall SCD Background : Intermittent pneumatic foot compression ( IPC ) is a useful technique for prophylaxis of peri‐operative venous thromboembolism . The aim of this study was to determine the effect of IPC on blood coagulation/fibrinolysis and platelet function using a blood viscometer ( SonoclotTM ) and a platelet aggregation monitor ( WBA analyzerTM ) , respectively . Using the same blood sample s , serum levels of tissue‐type plasminogen activator ( t‐PA ) , thrombomodulin ( TM ) and activated protein C ( APC ) were also measured The purpose of this study was to evaluate the efficacy of two intermittent pneumatic compression devices as prophylaxis against intravascular coagulation and leg swelling following total hip arthroplasty . We studied 121 patients by assessing thrombogenesis using the D-dimer level before and after total hip arthroplasty . In addition , the patients ’ postoperative swelling was evaluated by measuring the thigh and lower leg circumference . Altogether , 58 patients were assigned to the calf-thigh pneumatic compression group , and the other 63 were assigned to the plantar compression group ; the two pneumatic compression devices were compared to evaluate which was more effective for reducing thrombogenesis . At 7 days postoperatively , the mean D-dimer levels of the calf-thigh compression group and the plantar compression group were 8.86 and 9.26 µg/ml , respectively . There was no significant difference ( P = 0.697 ) between the two groups . However , the increased ratio of the circumference of the thigh , which was compared after arthroplasty , averaged 1.22 % in the calf-thigh compression group and 3.19 % in the plantar compression group , which was significantly different ( P ≪ 0.01 ) . Calf-thigh pneumatic compression was found to be more effective than plantar compression for reducing thigh swelling during the early postoperative stage A crossover study was performed to evaluate the effect of several pneumatic compression devices and active dorsoplantar flexion in 10 patients who underwent total hip arthroplasty . Using the Acuson 128XP/10 duplex ultrasound unit with a 5-MHz linear array probe , peak venous velocity and venous volume were assessed above and below the greater saphenous vein and common femoral vein junction . A computer generated r and omization table was used to determine the order of the test conditions . The pneumatic compression devices evaluated included two foot pumps , one foot and calf pump , one calf pump , and three calf and thigh pumps . Statistical analyses included analysis of variance and analysis of variance with covariance between devices and patients . The covariates tested were the baseline measurements and the order in which the devices were tested . Differences between devices relate in part to the frequency and rate of inflation and the location and type of compression . Pulsatile calf and foot and calf pneumatic compression with a rapid inflation time produced the greatest increase in peak venous velocity , whereas compression of the calf and thigh showed the greatest increase in venous volume . Because patient and nursing compliance is essential to the success of mechanical prophylaxis for thromboembolic disease , the more simple , yet efficacious , devices that are easier to apply and less cumbersome appear to have a greater likelihood of success . In the active and alert patient , active dorsoplantar flexion should be encouraged BACKGROUND AND OBJECTIVES Intermittent pneumatic compression ( IPC ) is an effective form of deep vein thrombosis prophylaxis for general surgery patients . The antithrombotic effect of IPC is thought to be the result of increased venous velocity and stimulation of endogenous fibrinolysis . However , the mechanism of enhanced fibrinolytic activity and the relative effects on normal and postthrombotic veins have not been defined . The purpose s of this study are 1 ) to quantify changes in fibrinolytic activity with IPC ; 2 ) to study the mechanism of fibrinolytic enhancement with IPC ; and 3 ) to evaluate whether postthrombotic patients have the same capacity for fibrinolytic enhancement with IPC as do normal subjects . METHODS Twelve volunteers ( 6 normal and 6 postthrombotic ) had 5 IPC devices applied for 120 minutes in r and om fashion , 1 per week x 5 weeks . The devices included single-chamber , sequential , foot , calf , and long-leg compression . Subjects had an indwelling antecubital venous cannula placed for blood drawn at baseline , 60 , 120 , and 180 minutes after IPC devices were applied . Global fibrinolytic activity ( euglobulin fraction , fibrin plate assay ) , tissue plasminogen activator ( tPA ) antigen ( Ag ) and activity ( Act ) , plasminogen activator inhibitor-1 ( PAI-1 ) Ag and Act , alpha-2-antiplasmin-plasmin complexes , and von Willebr and factor ( vWF ) antigen were assayed . RESULTS A striking elevation in fibrinolytic activity was noted at 180 minutes with all devices in normal subjects and postthrombotic patients ( p = 0.01 - 0.0001 ) ; however , baseline and stimulated fibrinolytic activity was attenuated in postthrombotic patients ( < 0.03 ) . The tPA-Act increased only in normal subjects ( 3.8 + /- 1.9 % ) ( p = 0.057 ) , despite a decrease in plasma tPA-Ag , which was observed in both normal subjects ( -12.4 + /- 3.8 % ) ( p = 0.009 ) and patients ( -17.2 + /- 3.1 % ) ( p = 0.001 ) . PAI-1-Ag decreased in both normal subjects ( -13.4 + /- 3.8 % ) ( p = 0.007 ) and patients ( -12.0 + /- 3.1 % ) ( p = 0.013 ) with a marked reduction in PAI-1-Act in both normal subjects ( p = 0.003 ) and patients ( p = 0.004 ) . There were no changes in vWF , and alpha-2-antiplasmin-plasmin complexes increased only in postthrombotic patients ( p = 0.021 ) . CONCLUSIONS Stimulation of endogenous fibrinolytic activity occurs after IPC , both in normal subjects and postthrombotic patients ; however , baseline and overall fibrinolytic response in postthrombotic patients is reduced . The mechanism of increased fibrinolytic activity is likely because of a reduction in PAI-1 , with a result ing increase of tPA activity After total hip ( THR ) or knee replacement ( TKR ) , there is still an appreciable risk of developing deep-vein thrombosis despite prophylaxis with low-molecular-weight heparin ( LMWH ) . In a prospect i ve , r and omised study we examined the efficacy of LMWH in combination with intermittent pneumatic compression in patients undergoing primary unilateral THR or TKR . We administered 40 mg of enoxaparin daily to 131 patients combined with either the use of intermittent pneumatic compression or the wearing of graduated compression stockings . Compression ultrasonography showed no evidence of thrombosis after LMWH and intermittent pneumatic compression . In the group with LMWH and compression stockings the prevalence of thrombosis was 28.6 % ( 40 % after TKR , 14 % after THR ) . This difference was significant ( p < 0.0001 ) . In the early post-operative phase after THR and TKR , combined prophylaxis with LMWH and intermittent pneumatic compression is more effective than LMWH used with graduated compression stockings |
749 | 15,023,713 | Data from Large Observational Studies on Independent Risk Factors for Positive Status on Tests for AntiHepatitis C Virus Antibody All 4 large population -based studies also found an independent association between HCV infection and high-risk sexual behaviors ( variably defined , but usually considered sex with multiple partners or sex with an HCV-infected person ) .
In most setting s with a low prevalence of intravenous drug use , high-risk sexual behaviors are the strongest risk factor for HCV infection ( 56 - 60 ) . | Hepatitis C virus ( HCV ) , the most common chronic bloodborne pathogen in the United States , is acquired primarily by large or repeated percutaneous exposures to blood ( 1 ) .
In the United States , approximately 2.3 % of adults 20 years of age or older are positive for anti-HCV antibody .
Between 55 % and 84 % of these have chronic infection ( 1 - 6 ) , but only 5 % to 50 % of infected adults are thought to know their status ( 7 - 9 ) .
In the United States , HCV is associated with approximately 40 % of cases of chronic liver disease and 8000 to 10000 deaths each year ( 1 ) .
Chronic HCV infection can also cause fatigue and decreased quality of life in the absence of cirrhosis or other complications ( 5 , 10 , 11 ) .
The natural course of chronic HCV infection varies .
Some patients never develop histologic evidence of liver disease even after decades of infection ( 12 , 13 ) .
Factors that may be associated with a more progressive course include older age at acquisition ( 14 , 15 ) ; comorbid medical conditions , such as heavy alcohol use ( 14 , 16 - 21 ) , HIV infection ( 22 - 24 ) , and other chronic liver disease ( 25 - 27 ) ; male gender ( 14 ) ; and longer duration of infection .
Mode of acquisition , viral load , aminotransferase levels , and viral genotype have not been consistently established as predictors of disease progression ( 28 - 31 ) .
The effects of ethnicity on the course of HCV infection have not been well studied in the United States ( 32 ) .
In this systematic review , commissioned by the U.S. Preventive Services Task Force ( USPSTF ) , we focus on whether it is useful to test for anti-HCV antibodies in asymptomatic adults who have no history of liver disease .
Risk Factor Assessment The identification of risk factors for the presence of HCV infection could aid in the development of selective screening strategies ( 8) .
Many other smaller , cross-sectional studies in a variety of specific population s support the strong association between HCV infection and intravenous drug use ( 39 - 51 ) .
Cross-sectional studies in intravenous drug users have reported prevalence rates ranging from 50 % to more than 90 % ( 52 - 56 ) .
Since 1992 , transfusions have not been an important mode of HCV transmission ( 56 , 67 , 68 ) .
Other retrospective studies have found that 53 % to 88 % of infected patients had identifiable risk factors ( 78 , 79 ) . | Interferon therapy may exacerbate health-related quality of life ( HRQL ) deficits associated with hepatitis C virus ( HCV ) early in the course of therapy . Treatment with polyethylene glycol-modified interferon ( peginterferon ) alfa-2a ( 40 kd ) provides improved sustained response over interferon alfa-2a , but its effect on HRQL is unknown . The objective of this study was to ( 1 ) evaluate the effect of sustained virologic response on HRQL in patients with HCV and ( 2 ) determine whether impairment of HRQL during treatment contributes to early treatment discontinuation . Data consisted of a pooled secondary analysis of patients ( n = 1,441 ) across 3 international , multicenter , open-label , r and omized studies that compared peginterferon alfa-2a ( 40 kd ) with interferon alfa-2a . ANCOVA was used to examine the effect of sustained virologic response on HRQL . Repeated- measures mixed-models ANCOVA was used to compare Fatigue Severity Scale ( FSS ) and SF-36 scores during treatment by treatment group . Logistic regression analysis was used to examine the association between changes at baseline in on-treatment HRQL and early treatment discontinuation . Sustained virologic response was associated with marked improvements from baseline to end of follow-up in all subjects , including patients with cirrhosis . During treatment , patients receiving peginterferon alfa-2a ( 40 kd ) had statistically significantly better scores on both the SF-36 and FSS . Baseline to 24-week changes in fatigue and SF-36 mental and physical summary scores significantly predicted treatment discontinuation . In conclusion , sustained virologic response is associated with improvements in quality of life in patients with or without advanced liver disease . This parameter may be an important consideration in maximizing treatment adherence The new Cobas Core Anti-HCV EIA was evaluated in two centers for its ability to detect antibodies directed to hepatitis C virus in human serum . This assay , which can be run fully automated on a r and om access analyzer , was compared with three other commercially available screening tests : the Ortho HCV 3.0 ELISA , the Murex anti-HCV , and the Abbott HCV EIA second generation . Positive or discrepant results were further investigated using the Wellcozyme HCV Western Blot or the Abbott Matrix HCV assays . The results obtained from analyzing 5045 serum sample s showed a high correlation between the Cobas Core Anti-HCV EIA and the other screening assays , ranging from 98.9 % to 99.9 % . Diagnostic specificities and sensitivities ranged from 99.7 % to 100 % and from 98.8 % to 100 % , respectively . In this study , the Cobas Core Anti-HCV EIA proved to be a very convenient test , able to perform at the highest levels of sensitivity and specificity The risk of complications from percutaneous liver biopsy is low , but discomfort is common and complications require hospitalization in approximately 4 % of patients . The optimal method of performing these biopsies is unknown . The goal of our study was to determine whether the use of ultrasonography in the biopsy room immediately prior to or during the procedure would lessen the risk of complications and to compare the safety and efficacy in obtaining tissue by use of a Trucut needle versus an automatic biopsy needle . Between 1992 and 1994 , 836 patients were entered into a r and omized study ( 489 in Rochester , MN ; 347 in Barcelona , Spain ) . Patients were r and omized immediately prior to liver biopsy into four groups : Trucut needle , or automatic biopsy needle , and with or without ultrasonography . Fisher 's Exact Test and a logistic regression model were also used to assess the effect of needle and ultrasonography on the odds for complications . The four biopsy groups were well-matched at entry with respect to age , sex , underlying liver disease , hemoglobin , prothrombin time , and platelet count . The use of ultrasound was associated with a decreased rate of hospitalization for pain , hypotension , or bleeding ( 2 vs. 9 , P < .05 ) . No difference in safety was found between the two types of needles . The number of passes needed to obtain specimens was similar for all four groups . The average length of the specimen was slightly greater with ultrasonographic-guided biopsies ( 1.7 mm vs. 1.6 mm , P < .05 ) and with biopsies obtained using the automatic biopsy needle when compared with the Trucut needle ( 1.7 mm vs. 1.5 mm , P < .05 ) , but this did not seem to be clinical ly important . The addition of ultrasonography reduces complications in patients undergoing percutaneous liver biopsy . The type of needle appears to offer little difference in safety or yield of diagnostic tissue . The use of ultrasonography for guidance of percutaneous liver biopsy will lead to a lower rate of complications . The value of this benefit must be weighed against the added cost of ultrasonographic guidance BACKGROUND A sustained virological response ( SVR ) rate of 41 % has been achieved with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this r and omised trial , peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin . METHODS 1530 patients with chronic hepatitis C were assigned interferon alfa-2b ( 3 MU subcutaneously three times per week ) plus ribavirin 1000 - 1200 mg/day orally , peginterferon alfa-2b 1.5 microg/kg each week plus 800 mg/day ribavirin , or peginterferon alfa-2b 1.5 microg/kg per week for 4 weeks then 0.5 microg/kg per week plus ribavirin 1000 - 1200 mg/day for 48 weeks . The primary endpoint was the SVR rate ( undetectable hepatitis C virus [ HCV ] RNA in serum at 24-week follow-up ) . Analyses were based on patients who received at least one dose of study medication . FINDINGS The SVR rate was significantly higher ( p=0.01 for both comparisons ) in the higher-dose peginterferon group ( 274/511 [ 54 % ] ) than in the lower-dose peginterferon ( 244/514 [ 47 % ] ) or interferon ( 235/505 [ 47 % ] ) groups . Among patients with HCV genotype 1 infection , the corresponding SVR rates were 42 % ( 145/348 ) , 34 % ( 118/349 ) , and 33 % ( 114/343 ) . The rate for patients with genotype 2 and 3 infections was about 80 % for all treatment groups . Secondary analyses identified bodyweight as an important predictor of SVR , prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight ( mg/kg ) . Side-effect profiles were similar between the treatment groups . INTERPRETATION In patients with chronic hepatitis C , the most effective therapy is the combination of peginterferon alfa-2b 1.5 microg/kg per week plus ribavirin . The benefit is mostly achieved in patients with HCV genotype 1 infections BACKGROUND Chronic hepatitis C virus ( HCV ) infection in patients with cirrhosis is difficult to treat . In patients with chronic hepatitis C but without cirrhosis , once-weekly administration of interferon modified by the attachment of a 40-kd branched-chain polyethylene glycol moiety ( peginterferon alfa-2a ) is more efficacious than a regimen of unmodified interferon . We examined the efficacy and safety of peginterferon alfa-2a in patients with HCV-related cirrhosis or bridging fibrosis . METHODS We r and omly assigned 271 patients with cirrhosis or bridging fibrosis to receive subcutaneous treatment with 3 million units of interferon alfa-2a three times weekly ( 88 patients ) , 90 microg of peginterferon alfa-2a once weekly ( 96 ) , or 180 microg of peginterferon alfa-2a once weekly ( 87 ) . Treatment lasted 48 weeks and was followed by a 24-week follow-up period . We assessed efficacy by measuring HCV RNA and alanine aminotransferase and by evaluating liver-biopsy specimens . A histologic response was defined as a decrease of at least 2 points on the 22-point Histological Activity Index . RESULTS In an intention-to-treat analysis , HCV RNA was undetectable at week 72 in 8 percent , 15 percent , and 30 percent of the patients treated with interferon alfa-2a and with 90 microg and 180 microg of peginterferon alfa-2a , respectively ( P=0.001 for the comparison between 180 microg of peginterferon alfa-2a and interferon alfa-2a ) . At week 72 , alanine aminotransferase concentrations had normalized in 15 percent , 20 percent , and 34 percent of patients , respectively ( P=0.004 for the comparison between 180 microg of peginterferon alfa-2a and interferon alfa-2a ) . In the subgroup of 184 patients with paired liver-biopsy specimens , the rates of histologic response at week 72 were 31 percent , 44 percent , and 54 percent , respectively ( P=0.02 for the comparison between 180 microg of peginterferon alfa-2a and interferon alfa-2a ) . All three treatments were similarly tolerated . CONCLUSIONS In patients with chronic hepatitis C and cirrhosis or bridging fibrosis , 180 microg of peginterferon alfa-2a administered once weekly is significantly more effective than 3 million units of st and ard interferon alfa-2a administered three times weekly Seroprevalence data from the Third National Health and Nutrition Examination Survey ( 1984 to 1999 ) suggest that 3 million persons in the United States are infected with the hepatitis C virus ( HCV ) ( 1 ) . Treatment fails to clear the virus in 80 % to 85 % of acutely infected persons . Not all persons who remain infected eventually develop progressive liver disease ( 2 ) , but in those who do , clinical evidence of liver damage may not appear until decades later ( 3 ) . It is widely believed that progression of liver disease in persons with chronic HCV infection is enhanced by concomitant heavy alcoholism ( 4 - 12 ) . We sought to quantify the association of transfusion-associated HCV infection and history of alcohol abuse with development of cirrhosis among patients followed from the time of acute HCV infection . Methods The source of this investigation , described in detail elsewhere ( 13 ) , is a long-term follow-up study of acute non-A , non-B hepatitis in patients included in earlier prospect i ve studies of transfusion-related HCV infection . All patients provided informed consent , and the study was approved by the relevant institutional review boards . Briefly , non-A , non-B hepatitis was identified by otherwise unexplained elevations in serum alanine aminotransferase ( ALT ) levels developing 2 to 24 weeks after transfusion , in the absence of serologic evidence of hepatitis A or B ( 13 ) . The ALT level had to be elevated on two consecutive measurements , and at least one of the values had to exceed twice the upper limit of normal . Stored sera from case- patients and controls from three of the prospect i ve studies the second Veterans Administration Cooperative study ( 14 ) , the Transfusion-Transmitted Viruses study ( 15 ) , and the National Institutes of Health Blood Bank Study (16)were tested for anti-HCV by enzyme immunoassay ( HCV EIA 2.0 , Abbott Laboratories , North Chicago , Illinois ) . Transfusion-associated HCV infection was diagnosed if anti-HCV appeared and persisted , was temporally related to elevated ALT levels , and was confirmed by using the supplementary recombinant immunoblot assay ( RIBA version 3.0 , Ortho Diagnostics , Raritan , New Jersey ) . Because repository sample s were not optimally stored for minimizing nucleic acid loss , HCV RNA testing was not performed . Controls consisted of transfused patients from the original three prospect i ve studies who had not developed hepatitis ( 13 ) . Controls were matched to case- patients by initial treatment center , sex , ethnicity , use of hepatitis immune globulin , presence or absence of a history of alcoholism , age , number of units of blood transfused , and date of transfusion . We excluded patients with anti-HCVpositive sample s that pre date d the index transfusion and those with anti-HCV reactivity but no confirmatory test . Anti-HCVpositive/RIBA-negative and anti-HCVnegative patients were classified as having transfusion-associated non-A , non-B , non-C hepatitis . Controls with anti-HCV in repository sample s were excluded . We used a multifaceted approach to gather information on each patient 's history of liver disease from participation in the prospect i ve studies through initiation of the follow-up study ( 13 ) . Vital status was ascertained through search es of death registries , and copies of death certificates were obtained . Patients or their design ated proxies ( if the patient was deceased or incompetent ) were invited to participate in a personal interview that included questions about previous hospitalizations . Authorization for release of medical records was obtained , and information on all hospitalizations at each facility identified was requested . Medical records , death certificates , and biopsy and autopsy reports were review ed by trained abstract ors for the diagnosis of cirrhosis , which was based on the occurrence of features of portal hypertension and overt clinical manifestations of cirrhosis . Evaluation of a sample of records indicated a high level of agreement between abstract ors and one of the investigators . Potential risk factors were derived primarily from personal interview . A composite variable aim ed at identifying a history of heavy alcohol abuse was design ed to minimize the possibility of misclassifying unexposed patients . The composite variable was based on one or more of the following criteria : loss of friends , family , or a job because of drinking ; admitting to ever having a problem with alcoholism ; evidence of heavy drinking abstract ed from medical records ; or quantification of usual intake of more than 80 g of alcohol per day during the years when the patient drank . Univariate methods ( the Fisher exact , exact FisherFreemanHalton [ 17 ] , and Wilcoxon rank-sum tests ) were used to compare the distribution of characteristics between patients included in and those excluded from the analysis and to examine associations between potential risk factors and development of cirrhosis . The strength of the association between risk factors and cirrhosis was assessed by using the odds ratio obtained from multiple logistic regression . The likelihood of developing cirrhosis associated with a combination of risk factors was estimated from the logistic model ( 18 ) . Results Of 1030 patients who were followed up from the original prospect i ve studies that had collected repository sample s , 836 ( 81.2 % ) were included in this analysis . We excluded 108 patients whose repository sample s were exhausted , 79 with ALT levels or HCV assays that did not permit reliable classification of hepatitis status , 1 with cirrhosis that pre date d the index transfusion , and 6 with data inconsistencies that could not be resolved . As shown in Table 1 , included and excluded patients differed only in median number of blood units originally transfused . The number of units received could affect the probability of developing acute transfusion-associated hepatitis or its severity but would probably not influence development of cirrhosis decades later . Table 1 . Characteristics of Included and Excluded Patients Preliminary analyses indicated that development of cirrhosis was unrelated to tattooing , ear piercing , occupational exposures , extended travel to areas in which hepatitis is endemic , and use of injection or other illegal drugs . Information on prescription drug use was unavailable for analysis . Development of cirrhosis differed ( P<0.05 ) according to transfusion-associated hepatitis status , study cohort , race/ethnicity , units of blood originally transfused , history of heavy alcohol abuse , and vital status at follow-up ( Table 2 ) . The absolute risk for developing cirrhosis was higher among patients with transfusion-associated HCV infection ( 17.0 % [ 35 of 206 patients ] ) ( P<0.001 ) than among those with transfusion-associated non-A , non-B , non-C hepatitis infection ( 3.2 % [ 3 of 95 patients ] ) or controls ( 2.8 % [ 15 of 535 patients ] ) but did not differ between the latter two groups ( P>0.2 ) . The median time from index transfusion to initiation of follow-up ( 15.6 years overall ) did not differ by cirrhosis status , transfusion-associated hepatitis status , or race/ethnicity ( P 0.10 ) . Table 2 . Association of Patient Characteristics with Development of Cirrhosis Logistic regression modeling indicated that patients with transfusion-associated HCV infection were 7.8 times ( 95 % CI , 4.0 to 15.1 times ) more likely to develop cirrhosis than controls , after adjustment for history of heavy alcohol abuse and study cohort . Patients with transfusion-associated non-A , non-B , non-C hepatitis were at increased risk for developing cirrhosis , but this finding was not significant ( odds ratio , 1.4 [ 95 % CI , 0.4 to 5.0 ] ) . Patients with transfusion-associated HCV were 5.6 times ( CI , 1.6 to 19.3 times ) more likely to develop cirrhosis than those with non-A , non-B , non-C hepatitis . A history of heavy alcohol abuse was associated with an increased risk for developing cirrhosis ( odds ratio , 4.0 [ CI , 2.1 to 7.7 ] ) . The HosmerLemeshow goodness-of-fit test indicated that the model fit the data well ( P>0.2 ) . From this model , it was estimated that patients with both transfusion-associated HCV infection and a history of heavy alcohol abuse were 31.1 times ( CI , 11.4 to 84.5 times ) more likely to develop cirrhosis than controls without a history of alcohol abuse . Patients with transfusion-associated non-A , non-B , non-C hepatitis and a history of heavy alcohol abuse were also more likely than controls without such a history to develop cirrhosis ( odds ratio , 5.5 [ CI , 1.3 to 24.3 ] ) . Although cirrhosis was less common among African-Americans ( 2.2 % ) than among persons of other ethnicities ( 7.2 % ) , addition of race/ethnicity , follow-up duration , units of blood originally transfused , vital status , and receipt of additional transfusions to the model changed the risks associated with hepatitis status and history of heavy alcohol abuse only slightly . None of these factors made a significant independent contribution to the model ( data not shown ) . Discussion Patients who contracted transfusion-associated HCV infection were at increased risk for developing cirrhosis ( odds ratio , 7.8 ) , and this risk increased substantially if the patient also had a history of heavy alcohol abuse ( odds ratio , 31.1 ) . Although numerous reports have identified a strong role of alcohol in promoting progression of liver disease among persons with chronic HCV infection ( 4 - 12 ) , our findings provide a quantitative measure to assess the strength of this association . Some patients who were originally classified as having acute non-A , non-B hepatitis tested negative for HCV infection . These patients developed cirrhosis more frequently than controls , but not significantly so . This finding suggests that the elevated ALT levels observed during the original prospect i ve studies were caused by intrinsic liver disease . It remains to be determined , however , whether these patients had been infected with a virus other than hepatitis A , B , or C virus or whether the elevated enzyme levels result ed from other causes ( for example , nonviral The prevalence of antibodies to hepatitis C virus ( anti-HCV ) , the behavioral and laboratory-derived risk factors for anti-HCV , and the quantity and homology of HCV RNA were assessed among 1039 non-injection drug-using sexually transmitted disease ( STD ) patients representing 309 sex partnerships . Thirty-seven ( 7 % ) of 555 males and 19 ( 4 % ) of 484 females had anti-HCV . In logistic regression analyses , factors associated with anti-HCV included age ( P < .001 ) , greater numbers of lifetime sex partners ( P = .023 ) , human immunodeficiency virus infection ( P < .001 ) , Trichomonas infection ( P < .001 ) , cigarette smoking ( P < .001 ) , and male homosexual exposure ( P = .012 ) . Among couples , females whose sex partners were anti-HCV positive were 3.7 times more likely to have anti-HCV than females whose sex partners were anti-HCV negative ( P = .039 ) . The proportion of RNA homology between anti-HCV positive females and their male partners ( 94 % ) was higher than among r and omly selected patients ( 82 % ) . Sexual transmission of HCV may contribute to the high prevalence of anti-HCV reported in urban setting The long-term outcome of patients with hepatitis C virus ( HCV ) infection is difficult to determine for several reasons . First , the initial bout of acute HCV infection is rarely recognized because of the paucity or complete absence of symptoms ( 1 ) . Second , even persons who have established chronic hepatitis are rarely symptomatic . Third , end-stage liver disease , when it occurs , can often take more than three decades to develop ( 2 , 3 ) . To address these issues , investigators have studied HCV infection in setting s that allow accurate determination of onset , such as transfusion-transmitted HCV ( 4 - 8 ) or outbreaks of HCV infection that can be attributed to receipt of contaminated immunoglobulin ( 9 , 10 ) . Several studies ( 9 - 12 ) have shown that major sequelae of chronic HCV infection , decompensated cirrhosis and hepatocellular carcinoma , are relatively uncommon . In contrast , clinical observations in tertiary care and liver transplantation centers suggest that chronic HCV infection is highly likely to have serious or fatal outcomes ( 2 , 3 , 13 , 14 ) . Some research ers believe that prospect i ve studies have been too short to accurately establish outcomes or , in the case of transfusion-related studies , have been limited by premature deaths due to the underlying illness . These concerns could be addressed by study ing young , healthy persons with laboratory-confirmed HCV infection for more extended periods . Through access to frozen serum specimens obtained during the late 1940s and early 1950s from more than 9000 healthy young persons , we were able to implement a retrospective cohort study spanning 45 years to determine liver-related morbidity and mortality in HCV-positive and HCV-negative persons . Methods The Repository Between 1948 and 1955 , epidemiologic and clinical studies were conducted at Fort Francis E. Warren Air Force Base , Wyoming , to investigate the problem of group A streptococcal infection and acute rheumatic fever among military recruits ( 15 , 16 ) . At the conclusion of the study , remaining serum specimens that had been collected from recruits were frozen in rubber-capped glass vials at 20 C. The specimens and the study records were archived by the original investigators . After the subsequent discovery of HCV ( 17 ) and the development of sensitive serologic assays , it became apparent that this unique collection of serum sample s could be a valuable tool for determining the long-term outcome of HCV-positive persons . The serum sample s had been stored frozen and unthawed for at least two decades . When we examined the collection in preparation for this study , we found that vials had been broken and specimens lost for only 0.5 % of the 9451 identified persons . The previously frozen sample s were separated into 1-mL aliquots and were refrozen at 20 C. One aliquot was used for all subsequent tests , and a computerized data base was generated . Serologic Assays Initial anti-HCV assays were performed in the Division of Pediatric Infectious Disease at the University of Minnesota , Minneapolis , Minnesota . Sample s from 9427 persons were assayed in duplicate for antibodies to HCV by third-generation enzyme-linked immunoassay ( EIA 3.0 ) ( Ortho Diagnostics , Raritan , New Jersey ) ( 18 ) . Repeatedly reactive sample s were analyzed by using supplemental recombinant immunoblot assay ( RIBA 3.0 , Ortho Diagnostics ) ; these tests were performed by the manufacturer . Sample s were then tested for HCV RNA by polymerase chain reaction ( 19 ) and by genotyping in the hepatitis research laboratory of the Veterans Affairs Medical Center in Washington , D.C. ( 20 ) . Persons were classified as having HCV infection if their serum sample s demonstrated antibodies to HCV on both EIA 3.0 and RIBA 3.0 . If an EIA-positive result yielded an indeterminate or negative result on RIBA 3.0 , the EIA 3.0 result was considered false-positive ( 21 ) . Serum aminotransferase levels were not measured because activity was probably lost through prolonged storage and because freeze-thaw cycles may have occurred after the original phlebotomy ( 22 ) . Construction of the Study Cohort The criteria for selection of recruits , the periods of observation , and the objectives of the original studies were defined in the original published reports ( 15 , 16 ) . During these studies , only names and military service numbers were recorded . We used this information to obtain additional data , such as Social Security numbers and demographic variables ( including age , ethnicity , and sex ) , from records of the Department of Defense , the National Archives and Records Administration , and the Department of Veterans Affairs . Our analysis was restricted to persons with identifiable Social Security numbers because this information was essential for documenting data on morbidity and mortality . Death certificate information was obtained from the Department of Veterans Affairs and through the National Death Index . Outcomes Morbidity Morbidity diagnoses were obtained from the Department of Veterans Affairs and the Health Care Financing Administration ( HCFA ) . Veterans Affairs data came from Patient Treatment Files , which code patients ' diagnoses at discharge from Veterans Affairs medical centers , and from documentation of disabilities in Compensation and Pension files . The HCFA data came from three files : the Medicare Provider Analysis and Review file , which includes information on diagnoses and procedures for each hospital discharge in the United States ; the Health Information Skeletonized Eligibility Write-off file , which records date s of birth and death that are abstract ed from Social Security records ; and the St and ard Analytical File , which provides data on out patients . Mortality We collected data on all-cause and cause-specific mortality from death certificates in Veterans Affairs cl aims files . The Department of Veterans Affairs maintains a computer file of beneficiaries , including recipients of veterans ' death benefits , and also records deaths that occur during hospitalizations in Veterans Affairs medical centers . Investigation of the extent of reporting has shown that the file is almost complete ( 23 ) . In some instances , we obtained evidence of death from HCFA files , which are derived from Social Security records . The National Death Index Plus service of the National Center for Health Statistics provided additional coded , cause-specific death certificate information from national mortality data . A qualified nosologist coded the underlying causes of death according to the rules that existed at the time of death and recoded them by using the International Classification of Diseases , Ninth Revision , Clinical Modification . Some death certificates and Veterans Affairs cl aims may be incomplete or inaccurate , but the frequency of these events should not differ between the HCV-positive and HCV-negative groups . Statistical Analysis Relative risks and CIs ( Cornfield and exact ) ( 24 ) and results of chi-square tests and the Fisher exact test were calculated by using Epi-Info , version 6.04 ( Centers for Disease Control and Prevention , Atlanta , Georgia ) ( 25 ) . A Kaplan-Meier survival analysis curve ( 26 ) was calculated by using SAS , version 6.12 ( SAS Institute , Inc. , Cary , North Carolina ) ( 27 ) . A P value less than 0.05 was considered statistically significant . Results Completeness of Identifier and Demographic Data Of 9427 persons , 8568 ( 91 % ) were included in our analysis because they had a Social Security number with which we could obtain information on morbidity and mortality . Most participants were white men who were younger than 25 years of age at the original phlebotomy . Of 6805 persons whose sex was known , 6742 ( 99 % ) were men . Among 6611 persons whose ethnicity was known , 89.3 % were white , 10.3 % were African American , and 0.4 % were Asian . The mean age of surviving cohort members as of 31 December 1996 was 64.8 years , and 95 % were between 60 and 69 years of age . Serologic Data Among the 8568 persons tested , 34 ( 0.4 % ) were repeatedly positive for anti-HCV . Seventeen of these 34 participants ( 50 % ) had positive results on RIBA 3.0 , 9 had indeterminate results , and 8 had negative results . Therefore , the prevalence of RIBA-confirmed anti-HCV reactivity was 0.2 % ( 17 of 8568 ) . At original phlebotomy , the mean age of the HCV-positive group was 21.5 years ( range , 19 to 28 years ; median , 20.5 years ) and the mean age of the HCV-negative group was 20.7 years ( range , 18 to 46 years ; median , 20.0 years ) . A significant difference was seen between the number of African-American persons with confirmed HCV infection ( 12 of 684 [ 1.8 % ] ) and the number of white persons with confirmed HCV infection ( 4 of 5902 [ 0.07 % ] ) ( relative risk , 25.9 [ CI , 8.4 to 80.0 ] ) . Polymerase chain reaction detected HCV RNA in 11 ( 65 % ) of the 17 persons who had positive results on EIA 3.0 and RIBA 3.0 but in no persons who had positive results on EIA 3.0 and indeterminate or negative results on RIBA 3.0 . Ten of the 11 persons who were positive for HCV RNA were classified as having genotype 1b . One person could not be classified . Morbidity Eight HCV-positive participants ( 47 % ) and 3566 HCV-negative participants ( 42 % ) had had at least one hospitalization , outpatient visit , or disease-related compensation award ( relative risk , 1.24 [ CI , 0.5 to 3.2 ] ) . One HCV-positive person had a liver-related diagnosis and was recorded as having chronic liver disease and cirrhosis ( Table 1 ) . Most of the 115 persons who were originally negative for HCV and had liver-related diagnoses were recorded as having chronic liver disease and cirrhosis . No HCV-positive persons had received a diagnosis of liver cancer or had been treated for liver cancer . One HCV-negative person had received outpatient treatment for liver cancer that was described on one occasion as primary and on another as not specified as primary or secondary . Table 1 . Liver-Related Hospitalizations , Outpatient Visits , and Compensation Awards among Persons with ( n=17 ) and Those without ( n=8551 ) Hepatitis C Virus Infection Mortality Through The natural history , prognosis , and clinical significance of chronic hepatitis C are highly variable and somewhat controversial . The purpose of this study was to evaluate the effect of chronic hepatitis C infection on patients ' perceptions of health‐related quality of life ( HRQOL ) and to evaluate whether treatment with interferon improves HRQOL . A total of 642 patients with compensated liver disease who were enrolled in a multicenter trial of interferon therapy for chronic hepatitis C had evaluation of HRQOL using the SF‐36 and other instruments derived from the Medical Outcomes Study ( MOS ) . These instruments were self‐administered by patients at baseline and at the end of a 24‐week post‐treatment observation period after 24 weeks of interferon treatment . Patients with chronic hepatitis C were compared with healthy controls ( n = 750 ) selected from a representative sample of adults in the United States . Unadjusted and age/gender‐adjusted results were similar , as were analyses using parametric or nonparametric methods . Compared with healthy controls , patients with chronic hepatitis C at baseline had lower HRQOL on all eight scales of the SF‐36 ( P < .001 for all ) . Patients without cirrhosis ( n = 284 ) showed similar although slightly smaller differences . The differences were highly significant , clinical ly and socially relevant , and greatest for those scales that were more reflective of physical than mental or emotional disease . Patients who had a sustained viral response to interferon therapy ( n = 41 ) exhibited marked improvements in HRQOL , and these improvements exceeded those of nonresponders on 13 of 14 HRQOL scales ( 8 were statistically significant ) . Similar improvements were noted in patients with sustained biochemical responses . The authors concluded that patients with chronic hepatitis C with or without cirrhosis have markedly reduced HRQOL . Patients who had a sustained response ( virological or biochemical ) to interferon therapy experienced significant improvements in perceived wellness and functional status . Successful interferon therapy provides meaningful improvements in HRQOL in patients with chronic hepatitis BACKGROUND Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus ( HCV ) infection . We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin , interferon alfa-2b plus ribavirin , and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. METHODS A total of 1121 patients were r and omly assigned to treatment and received at least one dose of study medication , consisting of 180 microg of peginterferon alfa-2a once weekly plus daily ribavirin ( 1000 or 1200 mg , depending on body weight ) , weekly peginterferon alfa-2a plus daily placebo , or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks . RESULTS A significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response ( defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy ) than of patients who received interferon alfa-2b plus ribavirin ( 56 percent vs. 44 percent , P<0.001 ) or peginterferon alfa-2a alone ( 56 percent vs. 29 percent , P<0.001 ) . The proportions of patients with HCV genotype 1 who had sustained virologic responses were 46 percent , 36 percent , and 21 percent , respectively , for the three regimens . Among patients with HCV genotype 1 and high base-line levels of HCV RNA , the proportions of those with sustained virologic responses were 41 percent , 33 percent , and 13 percent , respectively . The overall safety profiles of the three treatment regimens were similar ; the incidence of influenza-like symptoms and depression was lower in the groups receiving peginterferon alfa-2a than in the group receiving interferon alfa-2b plus ribavirin . CONCLUSIONS In patients with chronic hepatitis C , once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained virologic response , as compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone Administration of interferon ( IFN ) 3 times weekly in patients with chronic hepatitis C ( CHC ) is associated with low sustained responses , which may be , in part , related to this regimen 's inability to maintain IFN concentrations sufficient to suppress viral replication . An enhanced IFN molecule produced by the covalent attachment of a branched 40-kd polyethylene glycol moiety to IFN alpha-2a ( PEG[40kd ] IFN alpha-2a ) exhibits sustained absorption , a restricted volume of distribution , and reduced clearance compared with unmodified IFN alpha-2a . One hundred fifty-nine patients with CHC participated in a r and omized , ascending-dose ( 45 or 90 , 180 , 270 microg ) study comparing PEG(40kd ) IFN alpha-2a administered once weekly with 3 MIU IFN alpha-2a administered 3 times weekly for 48 weeks to determine the most appropriate PEG(40kd ) IFN alpha-2a dose for subsequent clinical trials . Efficacy was assessed by measuring hepatitis C virus ( HCV ) RNA following a 24-week treatment-free period . Sustained virological responses for PEG(40kd ) IFN alpha-2a once weekly were 10 % ( 45 microg ; not significant ) , 30 % ( 90 microg ; P = .009 ) , 36 % ( 180 microg ; P = .0006 ) , and 29 % ( 270 microg ; P = .004 ) , compared with 3 % for the 3-times-weekly 3-MIU IFN alpha-2a regimen . The types and frequencies of adverse events and laboratory abnormalities were similar among all groups . In conclusion , once-weekly PEG(40kd ) IFN alpha-2a was associated with a higher number of sustained virological responses compared with IFN alpha-2a 3 times weekly in patients with CHC , but had a similar safety profile . The 180-microg PEG(40kd ) IFN alpha-2a dose appeared to be the optimal dose based on sustained virological response and its associated side-effect profile OBJECTIVE : The treatment of hepatitis C virus ( HCV ) infection in United States veterans has become a major task for the Veterans Administration Healthcare System . Although the comprehensive diagnosis and treatment of HCV-infected patients has been m and ated , little is known about the performance characteristics of HCV clinics and about the outcomes of antiviral therapy in this unique patient population . METHODS : We retrospectively examined clinic show rates , treatment eligibility , and the response to antiviral therapy in a dedicated HCV outpatient clinic in a large urban Veterans Affairs medical center . RESULTS : Our data demonstrate that few veterans — regardless of their age or ethnic background —pursue evaluation and treatment of their HCV infection by hepatologists . A minority of those patients who undergo a comprehensive clinic evaluation meet the st and ard eligibility criteria for antiviral therapy . The overall efficacy of antiviral treatment , as measured by the sustained virological response rate , is substantially lower than previously reported in r and omized clinical trials . HCV-infected veterans are characterized by a unique combination of risk factors that are predictive of a poor response to antiviral therapy , including a preponderance of male gender , HCV genotype I , age > 40 yr , and histologically advanced degrees of liver disease . CONCLUSIONS : Our study demonstrates the limitations of outpatient HCV treatment initiatives in the United States veteran population , and suggests that the overall impact of current HCV treatment programs may be small BACKGROUND / AIMS Our objectives were : ( 1 ) to assess the clinical benefits and costs of performing ultrasound-guided liver biopsy with an automated needle compared to blind biopsy with a conventional Trucut needle in patients with chronic hepatitis C ; ( 2 ) to compare the histological yield of automated needles with Trucut needles . METHODS We prospect ively studied 166 patients with hepatitis C virus who underwent either ultrasound-guided biopsy using automated ASAP needles or blind biopsy using conventional Trucut needles . Both groups were matched for age , sex , cirrhosis , needle gauge and operator experience . Patient tolerance , complications and histological adequacy were assessed . In a separate in vitro study , we assessed the histological adequacy of liver biopsy specimens obtained using automated and Trucut needles from 10 fresh autopsy cases . RESULTS Ultrasound-guided biopsy caused significantly less biopsy pain ( 36.4 % vs. 47.3 % ; p < 0.0001 ) and significantly less pain-related morbidity ( 1.8 % vs. 7.7 % , p < 0.05 ) . Although , there was no significant difference in diagnostic yield between guided and blind biopsy ( 98 % vs. 94 % , p = 0.15 ) , 3 blind biopsies ( 3.3 % ) , including 2 which yielded extra-hepatic tissue , had to be repeated . The additional expense of performing guided liver biopsy with automated needles was 42 Irish Pounds per patient . In vitro , automated ASAP 15 G needles provided liver specimens comparable to Trucut 15 G needles and had the highest histopathologic score among the automated needles assessed . CONCLUSIONS Even in the absence of major complications , ultrasound-guided liver biopsy with an automated needle in HCV patients is safer , more comfortable and only marginally more expensive than blind Trucut biopsy BACKGROUND Covalent attachment of a 40-kd branched-chain polyethylene glycol moiety to interferon alfa-2a results in a compound ( peginterferon alfa-2a ) that has sustained absorption , a slower rate of clearance , and a longer half-life than unmodified interferon alfa-2a . We compared the clinical effects of a regimen of peginterferon alfa-2a with those of a regimen of interferon alfa-2a in the initial treatment of patients with chronic hepatitis C. METHODS We r and omly assigned 531 patients with chronic hepatitis C to receive either 180 microg of peginterferon alfa-2a subcutaneously once per week for 48 weeks ( 267 patients ) or 6 million units of interferon alfa-2a subcutaneously three times per week for 12 weeks , followed by 3 million units three times per week for 36 weeks ( 264 patients ) . All the patients were assessed at week 72 for a sustained virologic response , defined as an undetectable level of hepatitis C virus RNA ( < 100 copies per milliliter ) . RESULTS In the peginterferon group , 223 of the 267 patients completed treatment and 206 completed follow-up . In the interferon group , 161 of the 264 patients completed treatment and 154 completed follow-up . In an intention-to-treat analysis in which patients who missed the examination at the end of treatment or follow-up were considered not to have had a response at that point , peginterferon alfa-2a was associated with a higher rate of virologic response than was interferon alfa-2a at week 48 ( 69 percent vs. 28 percent , P=0.001 ) and at week 72 ( 39 percent vs. 19 percent , P=0.001 ) . Sustained normalization of serum alanine aminotransferase concentrations at week 72 was also more common in the peginterferon group than in the interferon group ( 45 percent vs. 25 percent , P=0.001 ) . The two groups were similar with respect to the frequency and severity of adverse events , which were typical of those associated with interferon alfa . CONCLUSIONS In patients with chronic hepatitis C , a regimen of peginterferon alfa-2a given once weekly is more effective than a regimen of interferon alfa-2a given three times weekly The aims of this study were the following : 1 ) to estimate the prevalence of hepatitis C virus ( HCV ) antibody ( anti-HCV ) in a population -based survey of French residents not selected for risk factors ; 2 ) to investigate the association between anti-HCV seropositivity , viremia , the infecting HCV genotype , and the alanine transaminase ( ALT ) level ; and 3 ) to identify risk factors for HCV infection by a nested case control study within this survey sample . The anti-HCV seroprevalence survey was performed in 6,283 volunteers ( 20- to 59-years-old ) r and omly selected from 45,377 consecutive individuals undergoing routine medical checkup in social security medical centers covering 4 of the 22 " regions " of France . Seventy-two volunteers were anti-HCV positive , a crude prevalence of 1.15 % . Fifty percent of these positive volunteers also had an abnormal ALT level and 81 % were HCV-RNA positive by polymerase chain reaction ( PCR ) . The prevalence weighted for age , sex , and place of residence was 1.05 % ( 95 % CI : 0.75 - 1.34 ) . The weighted prevalence was lower among men > 40-years-old ( 0.5 % ; 95 % CI : 0.1 - 1.0 ) and was close to 1 % in all other age and sex groups . Prevalence was inversely correlated with socioprofessional status with the highest rate being found among those with no paid employment ( 2.2 % ; 95 % CI : 1.3 - 3.0 ) . The HCV prevalence ( 1.7 % ; 95 % CI : 1.0 - 2.3 ) was highest in southeastern France . Seventy-eight percent of positive intervenous ( I.V. ) drug abusers were infected with HCV genotypes 1a or 3 , whereas 80 % of the transfusion-associated cases were infected by HCV genotypes 1b or 2a . Only three variables were significantly associated with HCV seropositivity in multivariate analysis : I.V. drug abuse ( 21 cases , 14 men all < 40-years-old ) , previous transfusion ( 22 cases , 18 women ) , and not having paid employment . Although routes of transmission other than I.V. drug abuse and transfusion may not be formally excluded they were not found to be statistically significant . Hepatitis C appears to be a major public health concern in France . A more active screening policy may be required because only 17 of 72 cases ( 24 % ) were aware of their HCV seropositivity before enrollment in the study BACKGROUND / AIMS Few data are available concerning the short and long-term effects of beta-IFN in patients with chronic hepatitis C. METHODOLOGY We r and omized 61 consecutive patients with HCV-related cirrhosis to receive : a ) natural beta-IFN with a 6 MU/tiw for 6 months followed by 3 MU/tiw for 6 months schedule or b ) no treatment . Biochemical and virological response was defined by normalization of ALT and negativization of serum HCV-RNA . Patients were followed-up for 5 years . RESULTS A biochemical end-of-therapy response ( ETR ) was observed in 5/38 patients ( 13 % ) who received beta-IFN compared to 2/23 ( 9 % ) of untreated cases , but a virological ETR appeared only in 4/38 ( 11 % ) treated cases . At long-term follow-up , 6 cases ( 16 % ) who received beta-IFN and 4 untreated ( 17 % ) developed a persistent normalization of alanine aminotransferase ( ALT ) but only 2 ( 5 % ) and 1 ( 4 % ) , respectively , were also HCV-RNA negative . The cumulative probability of liver decompensation ( variceal bleeding ascites or hepatic encephalopathy ) at 60 months was 24 % in treated and 35 % in untreated cases . Hepatocellular carcinoma developed in 2 treated and in 1 untreated patients . CONCLUSIONS beta-IFN therapy was not associated with a significant improvement either in biochemical or virological response in cirrhotic patients with chronic hepatitis C. No significant reduction of cirrhosis related clinical events was linked to treatment AIMS / BACKGROUND Many HCV RNA positive subjects with normal aminotransferase levels have significant liver damage despite normal liver biochemistry . In these patients it is not possible to discriminate between " healthy " carriers and subjects with chronic liver damage , unless liver biopsy is performed . The aim of this study was to evaluate the usefulness of HCV RNA quantitation as a non invasive tool to predict the severity of liver injury in a group of HCV carriers with normal amino-transferase levels . METHODS 59 HCV RNA positive subjects ( 20 males ) with persistently normal ALT levels were studied . All patients underwent HCV RNA quantitation and percutaneous liver biopsy . RESULTS No correlation was found between serum HCV RNA titers and grading , while viraemia did correlate with staging . Patients were categorized into four subgroups , according to arbitrary serum HCV RNA cut-offs . Grading was not different between the four groups . Staging was significantly higher among subjects with viraemia > 1000 x 10(3 ) copies/mL than in patients with HCV RNA titers < 1000 x 10(3 ) copies/mL. CONCLUSIONS In HCV carriers with normal aminotransferase levels viraemia does not predict the grade of HCV-related chronic liver disease ( CLD ) , although subjects with higher HCV RNA levels seem to have more severe fibrosis . Although these data suggest that patients with higher viraemia might have more intense architectural changes and more severe progression of liver disease than those with lower levels of HCV replication , the weak and imprecise correlation leads us to conclude that HCV RNA quantitation is not a useful indicator in clinical practice in the selection of patients for liver biopsy From August 1978 until March 1979 , 14 batches of anti-D immune globulin contaminated with hepatitis C virus ( HCV ) genotype 1b ( 20 , 000 - 480,000 copies/dose ) from a single erythrocyte donor had been administered for prophylaxis of rhesus isoimmunization throughout East Germany . All 2,867 women involved had been recalled after January 12 , 1979 for repeated screening of alanine transaminase ( ALT ) . They were prospect ively followed in regional centers . We have reexamined a cohort of 1,018 women ( median age 24 , range 16 - 38 years at infection ) on follow-up for 20 years in 9 representative centers . Within 6 months after anti-D administration , 10 % of these women had no evidence of disease and 90 % had acute hepatitis C ( n = 917 ) including 49 % with symptomatic and 22 % with icteric course . After 20 years , 85 % of the 917 affected women still tested positive for HCV antibodies ( among them 3 % responded to interferon treatment ) and 55 % were positive for HCV RNA ( among them 7 % were nonresponders to interferon and 3 % were apparent HCV carriers ) . Only 4 ( 0.4 % ) had overt cirrhosis . Two ( 0.2 % ) died of superinfected fulminant hepatitis B or alcoholism and cirrhosis , respectively . Histology obtained in 44 % of the viremic women showed hepatitis of minimal to moderate grade in 96 % , portal fibrosis in 47 % , and septal fibrosis in 3 % of the cases . In conclusion , formerly healthy young women , without hepatic comorbidity , may clear HCV ( 1b ) infection in half of the cases or develop mild chronic hepatitis C with low risk of progression to cirrhosis within 20 years BACKGROUND / AIMS The natural course of hepatitis C virus ( HCV ) replication in type C liver diseases has not yet been eluci date d. The aim of the study was to investigate the spontaneous outcome of the viremia by examining the changes in HCV RNA in patients with chronic type C liver diseases . METHODS Among patients who visited our liver clinic between June 1981 and December 1993 , 320 patients with chronic type C liver diseases were followed for at least 3 years and had no history of interferon treatment . HCV RNA was examined by a highly specific reverse transcription-polymerase chain reaction method in paired serum sample s obtained from these patients at the beginning and end of follow-up . RESULTS Among the 320 cases , HCV RNA was seropositive in 310 ( 97 % ) cases at the beginning of follow-up . Of these 310 , HCV RNA remained seropositive in 304 ( 98 % ) and became seronegative in six ( 2 % ) cases by the end of follow-up . All of these six patients had liver cancer . HCV RNA became seronegative after the patients entered the state of liver failure because of the development of tumors or portal thrombosis . The remaining 10 cases who were seronegative for HCV RNA at the beginning were seropositive at the end of follow-up . Among the 320 cases , serum alanine aminotransferase normalized and remained normal for more than 12 months until the end of follow-up in 11 cases ( 0.6%/year/case ) , but none became negative for HCV RNA . CONCLUSIONS Thus , during the natural course of chronic HCV infection , spontaneous negativation of serum HCV RNA seems extremely rare , at least in patients with chronic active hepatitis or cirrhosis of the liver , and may occur primarily at the terminal stage when tumors cause liver failure Cirrhosis is a frequent and severe event in the course of chronic hepatitis C , but it is unclear why some patients develop cirrhosis after a given period whereas others do not . We studied a large cohort of patients with chronic hepatitis C to determine the role of the route of transmission of hepatitis C virus ( HCV ) in the onset of cirrhosis . Six thous and six hundred sixty‐four patients were enrolled in a nationwide survey of chronic hepatitis C in France . We first r and omly defined a representative sample of 30 hospitals with medical units managing patients with HCV infection . All patients with chronic hepatitis C were enrolled if hepatitis C was diagnosed or treated in these units in 1991 , 1992 , or 1993 . A question naire was filled in from the patients ' charts and covered demographic data , risk factors for HCV infection , clinical and histological data , hepatitis B virus ( HBV ) and human immunodeficiency virus status , and alcohol intake . Descriptive statistics were prepared , and factors potentially related to the onset of cirrhosis were identified by means of univariate analysis followed by stepwise logistic regression analysis . Among the patients enrolled , 21.4 % had biopsy‐proven cirrhosis . Prevalence of cirrhosis markedly varied according to the route of transmission of HCV . It was significantly more frequent in blood recipients ( 23.4 % ) than in drug users ( 7.0 % ) . Although the occurrence of cirrhosis was dependent on disease duration , it remained more frequent in blood recipients than in drug users for a given duration . Apart from the route of transmission , excessive alcohol intake was also associated with a higher risk of cirrhosis ( 34.9 % vs. 18.2 % ; P < .001 ) , and so was HBV infection ( 24.6 % vs. 21.1 % ; P < .05 ) . These factors acted independently of the route of transmission . Hepatocellular carcinoma was observed in 3.6 % of all patients and in 17.8 % of cirrhotic patients , and its occurrence was strongly and mainly related to the presence of cirrhosis . In conclusion , cirrhosis occurred in about 20 % of the HCV‐infected patients in this study and was more frequent in blood recipients than in drug users , independently of disease duration . Expected changes in the epidemiology of HCV infection might modify the risk of developing cirrhosis and , thereafter , cancer BACKGROUND Hepatitis C virus ( HCV ) is a major cause of acute and chronic hepatitis in the United States and abroad . HCV antibody prevalences ranging from 10 to 90 % have been reported in intravenous drug abusers , hemodialysis patients , and persons suffering from other liver diseases , whereas HCV seropositivity rates for volunteer-blood donor population s are generally under 1 % . However no information has been available concerning the prevalence of HCV in general hospital population s in the United States . METHODS We examined the rate of HCV seropositivity in 530 patients admitted to the Atlanta VA Medical Center between November 1993 and November 1994 . The test population consisted of 400 r and om hospital admissions , 100 successive admissions to the surgical service , and 30 r and om admissions to the gastrointestinal service . Serum sample s were assayed for HCV antibodies by a second generation EIA , and all repeat reactives were re-examined using a supplemental research assay to confirm the presence of HCV antibodies . Complete chart review s were carried out on all HCV seropositive patients and on 100 HCV seronegative patients . RESULTS Sixty-two of the 530 patients tested ( 11.7 % ) were repeatedly positive for HCV antibodies . Of these 62 repeat reactives , 56 ( 90.3 % ) were positive and 3 others ( 4.8 % ) indeterminate by the supplemental assay . The HCV seropositivity rate after supplemental testing was 11.8 % for r and om admissions , 5.0 % for surgical admissions , and 13.3 % for patients admitted to the gastroenterology service . HCV-associated risk factors in HCV seropositive patients included a history of intravenous drug abuse , current or previous alcohol abuse , previous or concurrent liver disease , previous blood transfusions , hemodialysis , and multiple sex partners or unsafe sex . CONCLUSIONS HCV infection may be more prevalent among hospitalized VA patients ( and among other US hospital population s ) than previously expected The objectives of this study were to assess the safety , pharmacokinetics , and efficacy of pegylated interferon alfa-2b ( PEG-Intron ) plus ribavirin in patients with chronic hepatitis C. A total of 72 patients ( 35 men/37 women , age range 20 - 68 years ) with clinical ly compensated chronic hepatitis C virus ( HCV ) were enrolled into this open-label , r and omized , active controlled study . Patients received either PEG-Intron 0.35 , 0.7 , or 1.4 microg/kg subcutaneously weekly for 24 weeks alone , or in combination with ribavirin 600 , 800 , or 1,000 to 1,200 mg orally daily . Patients were evaluated during treatment and after a 24-week follow-up period for safety and efficacy . Detailed pharmacokinetic assessment s were performed at weeks 1 and 4 . PEG-Intron alone produced expected dose-related reductions in white cells , neutrophils and platelets . Addition of ribavirin reduced hemoglobin levels in a dose-related manner , did not further reduce PEG-Intron-induced decreases in neutrophil or white cell count , and increased platelet counts . Neutrophil function tests ( C5a and FMLP migration , killing curves ) were unaltered . Reported adverse events ( flu-like symptoms , asthenia ) were qualitatively similar in all dose groups . Anti-HCV activity , as measured by loss of detectable serum HCV RNA ( i.e. < 100 copies/mL ) at the end of treatment ( week 24 ) and after 24 weeks of follow-up ( week 48 ) showed dose-response trends for PEG-Intron . At each PEG-Intron dose level , anti-HCV activity was higher in patients coadministered ribavirin than in patients treated with PEG-Intron monotherapy . There was no evidence of pharmacokinetic interactions with either drug . We conclude that the safety and tolerability of combined PEG-Intron/ribavirin and PEG-Intron alone were comparable . Combined PEG-Intron/ribavirin showed dose-related synergistic anti-HCV effects , which were numerically superior to those obtained with PEG-Intron monotherapy The risk of a major complication from " blind " percutaneous liver biopsy is reported to be in the range of 0.24 % to 3.8 % . In a recent r and omized trial , patients whose liver biopsies were performed with ultrasonography had a significant reduction in complications requiring hospitalization compared with patients without ultrasound-guided biopsies ( 0.5 % vs. 2.2 % , P < .05 ) . Despite this , routine use of ultrasonography for liver biopsies has not been implemented because of controversies with respect to cost-effectiveness . The aim of our study was to analyze the relative cost-effectiveness of performing ultrasound-guided liver biopsies using decision analysis . A decision tree was constructed to compare a strategy of liver biopsy using ultrasonography with a strategy without ultrasonography . The major outcomes included were minor complications such as pain requiring analgesics and major complications , which require hospitalization . Costs included were direct medical costs from the payer 's perspective . In our baseline model , the cost from complications per patient with and without ultrasonography was $ 62 and $ 129 , respectively . The marginal effectiveness expressed as the number of major complications avoided was 1.2/100 liver biopsies . The incremental cost to avoid one major complication was $ 2,731 . The model was most sensitive to the frequency of major complications and the additional cost of ultrasonography . Our decision analysis model suggests that ultrasound-guided liver biopsy is cost-effective . Future studies assessing the efficacy of image-guided liver biopsies should be conducted The object of this study was to investigate the prevalence of Hepatitis C virus ( HCV ) by second-generation testing and to determine the effectiveness of risk factor-guided screening . We performed a prospect i ve study of HCV exposure determined by second-generation enzyme-linked immunoadsorbent assay ( ELISA ) and confirmed by radioimmunoblot assay ( RIBA ) . Risk factors ( RF ) were interpreted by univariate and multivariate analyses . Eight hundred eighty-six consecutive patients were tested for HCV over a 1-year period ; 34 women tested positive for HCV and 32 were confirmed by RIBA ( prevalence 3.6 % ) . Forty-nine percent of women had at least one RF . Age , intravenous drug use , history of hepatitis strongly correlated with HCV ( p < 0.001 ) . RF screening had a sensitivity of 81 % . Twenty-one percent of women with HCV had no RF . The absence of any RF had a negative predictive value of 98.7 % . RF screening is effective in identifying patients at low risk for HCV This international , r and omized , active‐controlled , parallel‐group , double‐blind dose‐finding study compared peginterferon alfa‐2b ( PegIntron ™ ) to interferon alfa‐2b for the initial treatment of compensated chronic hepatitis C. We r and omly assigned 1,219 subjects to receive either the st and ard three‐times‐weekly ( TIW ) interferon alfa‐2b dose ( 3 MIU ) or the once‐weekly ( QW ) peginterferon alfa‐2b ( 0.5 , 1.0 , or 1.5 μg/kg ) . Subjects were treated for 48 weeks and then followed for an additional 24 weeks . All 3 peginterferon alfa‐2b doses significantly ( P ≤ .042 ) improved virologic response rates ( loss of detectable serum HCV RNA ) after treatment and after follow‐up , as compared with interferon alfa‐2b . Unlike the end‐of‐treatment virologic response , the sustained virologic response rate was not dose‐related above 1.0 μg/kg peginterferon alfa‐2b because of a higher relapse rate among patients treated with 1.5 μg/kg peginterferon alfa‐2b , particularly among patients infected with genotype 1 . All 3 peginterferon alfa‐2b doses decreased liver inflammation to a greater extent than did interferon alfa‐2b , particularly in subjects with sustained responses . No new adverse events were reported , and the majority of adverse events and changes in laboratory values were mild or moderate . In conclusion , peginterferon alfa‐2b maintained ( 0.5 μg/kg ) or surpassed ( 1.0 , 1.5 μg/kg ) the clinical efficacy of interferon alfa‐2b while preserving its safety profile . The higher rate of virologic response during treatment with 1.5 μg/kg peginterferon alfa‐2b in patients infected with genotype 1 and high viral levels warrants further evaluation Percutaneous liver biopsy is a well-established diagnostic procedure . With the recent development of newer therapeutic modalities for liver diseases , including transplantation and -interferon for viral disease , the number of liver biopsies done for diagnosis and treatment follow-up will increase . Because of the high cost of hospitalization , outpatient liver biopsy is being recommended , provided it can be done safely [ 1 ] . The potential effect of doing liver biopsies on an outpatient basis could be considerable . For example , more than 90 % of the 23 374 cl aims for percutaneous liver biopsy su bmi tted to Medicare in 1990 [ 2 ] were for inpatient liver biopsy . Although a substitution of outpatient for in-hospital charges may not necessarily translate into equivalent savings , the potential effect on hospital bed use and re source allocation could be considerable . Despite the low incidence of complications from liver biopsy , the major concern in any such shift in practice is patient safety . A very large r and omized trial would be required to determine the differences in safety , if any , between inpatient and outpatient liver biopsies . At the Mayo Clinic , where most liver biopsies are done on out patients , the risk for hospitalization after liver biopsy is estimated to be 5 % [ 3 ] . However , the outcomes of patients admitted for possible complications have not been reported . To address the question of safety , we review ed the course of patients admitted after outpatient liver biopsy at the Mayo Clinic over a recent 2-year period . Methods Between 1 April 1989 and 1 April 1991 , 430 liver biopsies were done in the division of gastroenterology . Only 25 of these were inpatient biopsies ; the remaining 405 were outpatient biopsies . All biopsies were done for the evaluation of chronic liver diseases ( Table 1 ) . The most frequent indications were the diagnosis and staging of primary biliary cirrhosis ( 40 % ) , chronic active hepatitis ( 27 % ) , and primary sclerosing cholangitis ( 14 % ) . Alcoholic liver disease accounted for only 5 % of the biopsies . Hemochromatosis , 1-antitrypsin deficiency , and other chronic diseases each accounted for a small proportion of the biopsies . It has been the policy at the Mayo Clinic over the past few years to have all mass lesions biopsied under imaging guidance in the department of radiology . This is because biopsies of mass lesions seem to carry a higher risk for bleeding complications than those done for diagnosis of chronic liver diseases , and this risk is directly related to the number of passes required to obtain diagnostic tissue [ 4 ] . Hence , the approximately 300 biopsies of mass lesions were not included in our analysis . Postorthotopic liver transplant biopsies were also not included because they ( approximately 200 per year ) are done using a different protocol . St and ard criteria for outpatient liver biopsy include the requirement that patients have a hemoglobin greater than 100 g/L ( 10.0 g/dL ) , a platelet count greater than 50 109/L , and a prothrombin time less than 14.0 seconds ( with control values of 10.2 to 12.3 seconds ) . Table 1 . Final Diagnoses in Patients Who Had Liver Biopsy during a 1-Year Period The biopsies were done by trainees in gastroenterology ( postgraduate years 4 to 6 ) or a gastroenterology staff physician . A Tru-Cut ( Baxter , Valencia , California ) needle was used in 92 % of the biopsies and a Jamshidi or Klatskin needle in the rest . More than one pass was generally done if diagnostic tissue was not obtained on the first pass . After the procedure , the patient was asked to lie flat , and the vital signs were checked every 15 minutes for 3 hours . Patients were then allowed to leave the outpatient area if no problems occurred , but they were required to remain in the Rochester area for at least 24 hours . Reasons considered to justify admission were the development of fever ; orthostatic hypotension ; peritoneal signs ; localized , persistent nonperitoneal pain ; or lightheadedness , even without demonstrable change in vital signs . If complications occurred , patients were immediately hospitalized . An admission hemoglobin and 24-hour hemoglobin were obtained from all hospitalized patients . Further imaging after biopsy was obtained in cases of persistent pain , persistent or severe orthostatic hypotension , or decreasing hemoglobin levels . Results Thirteen patients were admitted with complications , which represented 3.2 % of all patients undergoing outpatient liver biopsy during this period ( Table 2 ) . All complications were noted during the first 3 hours after biopsy . In patients admitted for complications , all biopsies had been done using a Tru-Cut needle , with an average of 1.2 passes . However , the number of passes was not statistically related to the occurrence of hemorrhage . Ten ( 77 % ) of those admitted had their liver biopsies done by fellows , who did 86 % of the biopsies . Biopsies in the remaining three patients were done by staff gastroenterologists . The prothrombin time was normal in all patients , and the platelet counts were greater than 140 109/L in all patients except one , who had a platelet count of 65 109/L. Table 2 . Outcomes in Patients with Complications after Outpatient Liver Biopsy * Five patients ( 38 % ) were admitted for persistent pain only ( see Table 2 ) . Of these patients , only one had a decrease in hemoglobin greater than 10 g/L ( 1 g/dL ) during a 24-hour period . Four of the five patients had an imaging study of the liver ( computed tomography [ one patient ] or ultrasound [ three patients ] ) after biopsy , including the patient with a decrease in hemoglobin . Two complications , a small subcapsular hematoma and an echogenic gallbladder consistent with hemobilia were found in two patients who showed no decrease in hemoglobin concentration . The remainder of the imaging studies were negative . No one in this group received blood transfusions . Two patients , including the one with the subcapsular hematoma , received narcotics ( each received meperidine hydrochloride , 100 mg total ) . No additional management , such as chest tube placement or surgery , was required . Five patients ( 38 % ) were admitted for orthostatic hypotension and one patient was admitted for hypotension and pain ( 8 % ) ( see Table 2 ) . Five of these six patients had a decrease in hemoglobin of more than 10 g/L [ 1 g/dL ] in a 24-hour period . The one patient was simply observed overnight . Three patients ( including the patient with hypotension and pain ) had a follow-up computed tomographic scan , which revealed an area of bleeding . One patient had a hemothorax , one patient had a subcapsular hematoma , and one patient had both a subcapsular hematoma and a hemothorax . The patient with the hemothorax and the patient with the subcapsular hematoma received 2 and 4 units of blood , respectively . No invasive management , such as chest tube placement or surgery , was required . One patient was admitted for peritoneal signs but did not have hypotension or a decrease in hemoglobin concentration ( see Table 2 ) . Abdominal computed tomographic scan after liver biopsy showed no evidence of bleeding . His pain was presumed secondary to post-biopsy bile peritonitis . One other patient was admitted for lightheadedness and an increase in blood pressure . This patient , observed overnight , was free of complications and discharged . The average length of the hospital stay was 1.5 days . All 13 patients did well and required no further intervention . Discussion The effectiveness of liver biopsy in altering treatment and disease outcome was once arguable because of limited treatment modalities for chronic liver disease . During the period of our study , the importance of liver biopsy , not just for diagnosis , but for therapeutic decisions and for monitoring has grown . This is reflected in exp and ed treatment options such as ursodeoxycholic acid for primary biliary cirrhosis and primary sclerosing cholangitis , the use of -interferon for viral disease , and liver transplantation . A skillfully done percutaneous liver biopsy has a relatively low rate of complications . Average mortality rates of 0.01 % to 0.1 % and morbidity rates of 0.1 % have been reported [ 5 - 8 ] . The reported rate of major complications , including hemorrhage , bile leak , hemothorax , and perforation of abdominal viscera , for our institution was 3.2 % [ 4 ] . Delayed complications , such as bleeding noted after 24 hours , are extremely rare . In one study of 68 276 liver biopsies , such complications were detected in only four patients , none of whom required treatment [ 8 ] . This finding suggests that a 24-hour observation period after biopsy should be sufficient . During the past 10 years , most liver biopsies have been done on an outpatient basis , in conformance with recommendations outlined by the American Gastroenterological Society [ 1 ] . In the absence of a large r and omized study comparing the safety of inpatient and outpatient biopsies , the low rate of severe complications and the rarity of delayed complications make outpatient liver biopsy a valid consideration if complications are easily recognizable , occur early , and are limited . Of the 405 patients undergoing outpatient biopsy during the study period , only 13 ( 3.2 % ) required admission . Most patients ( 92 % ) were admitted for pain or hypotension . The most worrisome complication was hemorrhage . A decrease of more than 10 g/L ( 1 g/dL ) in hemoglobin was noted in 6 of 13 patients , and 5 bleeding sites were radiologically identified ( see Table 1 ) . However , when bleeding occurred after liver biopsy , it was noted early , required no invasive management , and led to no deaths . All complications became manifest within the 3-hour period of close observation after liver biopsy , a finding that is consistent with previous studies [ 8 , 9 ] . Transfusions , narcotics , or invasive management was rarely needed . It has been our policy recently to require that those undergoing outpatient liver biopsy be able to return within 30 minutes to the site where the procedure is done . It has also been requested that during Nine thous and two hundred twelve liver biopsies were performed according to a defined protocol , and data were prospect ively recorded to identify risk factors for major bleeding . There were 10 fatal and 22 nonfatal hemorrhages ( 0.11 % and 0.24 % , respectively ) . By comparison with a control group that did not hemorrhage , malignancy , age , sex , and the number of passes were the only predictable risk factors . The risk of fatal hemorrhage in patients with malignancy is estimated to be 0.4 % ; for nonfatal hemorrhage , 0.57 % . In patients undergoing liver biopsy for nonmalignant disease , the risks are 0.04 % and 0.16 % , respectively A nationwide prospect i ve study was conducted in France in 89 university and primary referral hospitals ' liver units to evaluate practice s of liver biopsy and the occurrence of complications . A total of 2,084 biopsies were analyzed , recording the indication , hemostasis parameters , experience of operator , route of biopsy , use of ultrasonography ( US ) , type of hospitalization , side effects , and complications . Pain , anxiety , and discomfort were evaluated by patients by visual analogue scale ( VAS ) . Biopsies were performed by experienced physicians ( > 150 procedures performed ) in 72 % , and hepato‐gastroenterologists in 89 % of the cases . Hepatitis C was the indication in 54 % . Sedation or premedication ( atropine ) was given in 46 % . US‐guidance was used in 56 % of the cases . A day‐care procedure was used in 27 % . No deaths occurred , but severe complications were observed in 0.57 % and increased with the number of passes and decreased with experience of operator , use of atropine , and US‐guidance . Pain was independently related to general anesthesia , experience of the operator , female sex , and hepatitis C. Anxiety was increased in women . Discomfort was increased by venous access and decreased with an experienced operator . Acceptance of additional biopsies was related to a day‐care procedure and independently related to general anesthesia and multiples passes . This study showed that ( 1 ) liver biopsy procedures vary greatly in France , ( 2 ) hepatitis C is the main indication for liver biopsy at present , ( 3 ) US‐guidance should be developed to reduce severe complications , and ( 4 ) day‐care procedures increase acceptance of a future biopsy and should also be used more often To assess the effect of human immunodeficiency virus ( HIV ) immunosuppression on ongoing hepatitis C virus ( HCV ) infection , CD4 lymphocyte counts and serum concentrations of HCV RNA , HIV RNA , and alanine aminotransferase ( ALT ) were evaluated among members of a cohort of injecting drug users ( IDUs ) . With 100 participants r and omly selected at various stages of HIV-related immunosuppression , serum HCV RNA concentrations increased with age ( P = .007 ) and were higher in HIV-positive IDUs with 201 - 500 ( P = .026 ) and 51 - 200 ( P = .004 ) CD4 cells/mL than in HIV-negative participants . Among 27 HCV-infected IDUs who acquired HIV infection , serum HCV RNA concentrations varied between semiannual visits by a mean of 0.45 logs , increasing by 0.60 logs after HIV seroconversion ( P < .0001 ) , by 0.12 logs each subsequent year ( P = .006 ) , and by 0.36 logs per log increase in CD4 cells ( P = .01 ) . Serum ALT levels were similar between HIV-positive ( 40.1 IU/mL ) and HIV-negative ( 45.4 IU/mL ) patients ( P > .10 ) . While HIV infection and possibly HIV progression are associated with increased HCV RNA levels , other factors appear to affect biochemical and virologic markers of HCV infection in some dually infected persons BACKGROUND Mother-to-infant transmission of hepatitis C virus ( HCV ) could become the main route of HCV infection in the future because there are no methods available to prevent vertical infection . The aim of this study was to determine the incidence of mother-to-infant transmission in infants born to mothers who tested positive for anti-HCV antibodies and to eluci date associated risk factors for transmission . METHODS Screening was conducted for 16,800 pregnant women with an anti-HCV antibodies test , and 154 mothers were positive . From the positive group 141 mothers were enrolled in the study and their 147 infants were followed from birth for serum alanine aminotransferase activity , anti-HCV antibodies and HCV RNA . HIV infection was tested in 73 of 141 mothers , all of whom were negative . RESULTS Thirty-three infants were dropped from the study because they were followed for < 6 months or were not tested adequately . Of the 114 infants finally evaluated 9 ( 7.8 % ) had detectable HCV RNA . The transmission rate was not influenced by the mode of delivery [ vaginal delivery , 8 of 90 vs. cesarean section , 1 of 24 ( P = 0.396 ) ] or by the type of feeding [ 9 of 98 for breast-fed infants vs. 0 of 16 for formula-fed infants ( P = 0.243 ) ] . All infected infants were born to mothers who had HCV viremia at the delivery ( P = 0.040 ) and to those with a high viral load ( P = 0.019 ) . CONCLUSIONS Our prospect i ve study showed that the transmission rate of mother-to-infant HCV infection was 7.8 % in anti-HCV antibody-positive mothers . Risk was related to the presence of maternal HCV viremia at delivery and a high viral load in the mothers |
750 | 23,803,126 | However , there was no significant reduction in fractures .
Currently , our meta- analysis suggested that oral and intravenous bisphosphonates caused a rapid increase in spine and hip or femoral BMD in non-metastatic prostate cancer patients receiving and rogen-deprivation therapy .
Fever and gastrointestinal symptoms were common with the use of bisphosphonates .
These short-term trials ( maximum of 12 months ) did not show fracture reduction . | This systematic review was conducted to assess the efficacy and safety of bisphosphonates for prevention and treatment of osteopenia or osteoporosis in men with non-metastatic prostate cancer receiving and rogen- deprivation therapy . | BACKGROUND Treatment with a gonadotropin-releasing hormone agonist decreases bone mineral density and increases the risk of fracture in men with prostate cancer . We conducted a controlled study of the prevention of osteoporosis in men undergoing treatment with a gonadotropin-releasing hormone agonist . METHODS In a 48-week , open-label study , we r and omly assigned 47 men with advanced or recurrent prostate cancer and no bone metastases to receive either leuprolide alone or leuprolide and pamidronate ( 60 mg intravenously every 12 weeks ) . Bone mineral density of the lumbar spine and the proximal femur was measured by dual-energy x-ray absorptiometry . Trabecular bone mineral density of the lumbar spine was measured by quantitative computed tomography . Forty-one men completed the study . RESULTS In men treated with leuprolide alone , the mean ( + /-SE ) bone mineral density decreased by 3.3+/-0.7 percent in the lumbar spine , 2.1+/-0.6 percent in the trochanter , and 1.8+/-0.4 percent in the total hip , and the mean trabecular bone mineral density of the lumbar spine decreased by 8.5+/-1.8 percent ( P<0.001 for each comparison with the base-line value ) . In contrast , the mean bone mineral density did not change significantly at any skeletal site in men treated with both leuprolide and pamidronate . There were significant differences between the two groups in the mean changes in bone mineral density at 48 weeks in the lumbar spine ( P<0.001 ) , trochanter ( P = 0.003 ) , total hip ( P=0.005 ) , and trabecular bone of the lumbar spine ( P=0.02 ) . CONCLUSIONS Pamidronate prevents bone loss in the hip and lumbar spine in men receiving treatment for prostate cancer with a gonadotropin-releasing hormone agonist Bone mineral density ( BMD ) and bone mineral content ( BMC ) were measured in the femoral neck area , trochanteric area and Wards triangle , and in the distal radius of the left forearm before and after 1 year of endocrine treatment in 27 patients with prostatic cancer . Eleven of the patients were treated with orchidectomy and 16 with combined oral and intramuscular estrogens . The patients were free from metastases during the entire observation period . In the orchidectomized patients , BMD and BMC of the distal radius decreased significantly following treatment , whereas no changes were observed in the estrogen-treated patients . These preliminary results demonstrate that estrogens may protect bone in male subjects also and may merit further investigations on larger groups of patients PURPOSE And rogen deprivation therapy is associated with fracture risk in men with prostate cancer . We assessed the effects of toremifene , a selective estrogen receptor modulator , on fracture incidence in men receiving and rogen deprivation therapy during a 2-year period . MATERIAL S AND METHODS In this double-blind , placebo controlled phase III study 646 men receiving and rogen deprivation therapy for prostate cancer were assigned to toremifene ( 80 mg by mouth daily ) and 638 were assigned to placebo . Subjects were followed for 2 years . The primary study end point was new vertebral fractures . Secondary end points included fragility fractures , bone mineral density and lipid changes . RESULTS The 2-year incidence of new vertebral fractures was 4.9 % in the placebo group vs 2.5 % in the toremifene group , a significant relative risk reduction of 50 % ( 95 % CI -1.5 to 75.0 , p = 0.05 ) . Toremifene significantly increased bone mineral density at the lumbar spine , hip and femoral neck vs placebo ( p < 0.0001 for all comparisons ) . There was a concomitant decrease in markers of bone turnover ( p < 0.05 for all comparisons ) . Toremifene also significantly improved lipid profiles . Venous thromboembolic events occurred more frequently with toremifene than placebo with 7 subjects ( 1.1 % ) in the placebo group experiencing a venous thromboembolic event vs 17 ( 2.6 % ) in the toremifene group . Other adverse events were similar between the groups . CONCLUSIONS Toremifene significantly decreased the incidence of new vertebral fractures in men receiving and rogen deprivation therapy for prostate cancer . It also significantly improved bone mineral density , bone turnover markers and serum lipid profiles PURPOSE Gonadotropin-releasing hormone ( GnRH ) agonists decrease bone mineral density ( BMD ) and increase fracture risk in men with prostate cancer . Annual zoledronic acid increases BMD in postmenopausal women , but its efficacy in hypogonadal men is not known . PATIENTS AND METHODS In a 12-month study , 40 men with nonmetastatic prostate cancer who were receiving a GnRH agonist and had T scores more than -2.5 were r and omly assigned to zoledronic acid ( 4 mg intravenously on day 1 only ) or placebo . BMD of the posteroanterior lumbar spine and proximal femur were measured by dual-energy x-ray absorptiometry . RESULTS Mean ( + /- SE ) BMD of the posteroanterior lumbar spine decreased by 3.1 % + /- 1.0 % in men assigned to placebo and increased by 4.0 % + /- 1.0 % in men assigned to zoledronic acid ( P < .001 ) . BMD of the total hip decreased by 1.9 % + /- 0.7 % in men assigned to placebo and increased by 0.7 % + /- 0.5 % in men assigned to zoledronic acid ( P = .004 ) . Similar between-group differences were observed for the femoral neck and trochanter . Serum N-telopeptide , a marker of osteoclast activity , decreased significantly after zoledronic acid treatment . CONCLUSION In men receiving a GnRH agonist , a single treatment with zoledronic acid significantly increased BMD and durably suppressed serum N-telopeptide levels for 12 months . Annual zoledronic acid may be a convenient and effective strategy to prevent bone loss in hypogonadal men To report a r and omized , placebo‐controlled study of treatment with zoledronic acid every 3 months in patients with hormone‐sensitive prostate cancer , both with and without bone metastases , to assess the effect on bone mineral density ( BMD ) and markers of bone turnover PURPOSE And rogen deprivation therapy for prostate cancer is associated with osteoporosis and increased fracture risk . Previous studies of zoledronic acid demonstrated bone loss prevention in patients initiating and rogen deprivation therapy . There are limited data on patients on prolonged and rogen deprivation therapy or in Veterans Affairs patients with multiple risk factors for osteoporosis . METHODS We r and omized 93 patients with M0 prostate cancer in this placebo controlled trial in the Veterans Affairs health care system . Preplanned strata included 50 patients on and rogen deprivation therapy for less than 1 year ( stratum 1 ) and 43 on and rogen deprivation therapy for greater than 1 year ( stratum 2 ) . In each stratum patients were r and omized to 4 mg zoledronic acid intravenously every 3 months for 4 treatments or intravenous placebo . The primary end point was the percent change in bone mineral density at the lumbar spine at 12 months . RESULTS Age , race , body mass index and osteoporosis risk factors were similar for the 2 treatments . Most patients were former smokers , had moderate alcohol intake , were not on calcium/vitamin D supplements and were relatively sedentary at baseline . In stratum 1 spine bone mineral density increased 5.95 % in the zoledronic acid arm and decreased 3.23 % in the placebo arm ( p = 0.0044 ) . In stratum 2 spine bone mineral density increased 6.08 % in the zoledronic acid arm and only increased 1.57 % in the placebo arm ( p = 0.0005 ) . Treatment was well tolerated with minimal impact on renal function . CONCLUSIONS Zoledronic acid improved bone mineral density in patients with M0 prostate cancer on and rogen deprivation therapy for 1 year or less , or greater than 1 year . This finding indicates that bisphosphonate therapy remains effective when initiated later in the course of and rogen deprivation therapy and is efficacious in Veterans Affairs patients with multiple risk factors for osteoporosis UNLABELLED Today , and rogen deprivation therapy is a cornerstone of treatment for advanced prostate cancer , although it presents important complications such as osteoporosis . Neridronate , a relatively new bisphosphonate , is able to prevent bone loss in patients with prostate cancer during and rogen ablation . INTRODUCTION And rogen-deprivation therapy ( ADT ) is a cornerstone of treatment for advanced prostate cancer . This therapy has iatrogenic complications , such as osteoporosis . The aim of our study was to evaluate the efficacy of neridronate , a relatively new bisphosphonate , to prevent bone loss during and rogen ablation . MATERIAL S AND METHODS Forty-eight osteoporotic patients with prostate cancer , treated with 3-month depot triptorelina , were enrolled and r and omly assigned to two different treatment groups : group A ( n = 24 ) was treated with a daily calcium and cholecalciferol supplement ( 500 mg of elemental calcium and 400 IU cholecalciferol ) , and group B ( n = 24 ) received in addition to the same daily calcium and cholecalciferol supplement , 25 mg of neridronate given intramuscularly every month . All patients also received bicalutamide for 4 weeks . Lumbar and femoral BMD was evaluated by DXA at baseline and after 1 year of therapy ; moreover , deoxypyridinoline ( DPD ) and bone alkaline phosphatase ( BALP ) were determined at the beginning , midway through , and at the end of the study . RESULTS After 6 and 12 months , whereas patients treated only with calcium and cholecalciferol ( group A ) showed a marked bone loss , with increased levels of DPD and BALP compared with baseline values , patients treated also with neridronate ( group B ) had substantially unchanged levels of these markers . After 1 year of treatment , lumbar and total hip BMD decreased significantly in patients treated only with calcium and cholecalciferol ( group A ) , whereas it did not change significantly at any skeletal site in patients treated also with neridronate ( group B ) . No relevant side effects were recorded during our study . CONCLUSIONS Neridronate is an effective treatment in preventing bone loss in the hip and lumbar spine in men receiving ADT for prostate cancer Objectives : Long-term results of radiotherapy in locally advanced prostate cancer are poor due to local and distant failures . Since prostate cancer is hormone dependent , tumor and rogen deprivation may enhance tumor eradication . Methods : Three r and omized phase III trials , RTOG and EORTC are reported : they assess and rogen suppression by using a luteinizing hormone-releasing hormone analogue ( LH-RHa ) with or without and rogen blockade before and during , or during and after external irradiation . Results : A gain in disease-free , local relapse-free and metastasis-free survival has been obtained ( p < 0.001 ) . Only the EORTC 22863 trial has reported a significant improvement in overall survival ( p = 0.001 ) with an LH-RHa started the first day of radiotherapy and administered every 4 weeks over 3 years . In the RTOG 85 - 10 trial , and LH-RHa , initiated in the last week of radiation therapy and continued until relapse , increased overall survival only in patients with poorly differentiated tumor with a Gleason score of 8–10 ( p = 0.03 ) . Conclusion : And rogen suppression prior to and during radiation improves disease-free survival ; adjuvant hormonal therapy with an LH-RHa during and after radiation improves overall survival OBJECTIVE And rogen-deprivation therapy ( ADT ) is the usual treatment for locally advanced or metastatic prostate cancer . Osteoporosis is a common complication of ADT . The aim of our study was to evaluate the efficacy of neridronate , a relatively new bisphosphonate to prevent bone loss during and rogen ablation . METHODS Sixty patients with prostate cancer and osteoporosis were enrolled and r and omly assigned to 2 different treatment regimes : group A ( 30 patients ) treated with maximum and rogenic blockage ( MAB ) , and group B ( 30 patients ) treated with bicalutamide 150 mg . Each group was divided in 2 subgroups A1-A2 and B1-B2 . All patients received calcium and cholecalciferol supplements ( 500 mg of elemental calcium and 400 IU cholecalciferol ) daily . The A2 and B2 subgroups were also treated with neridronate ( 25 mg intramuscular monthly ) . Lumbar and femoral bone mineral density ( BMD ) was evaluated by dualenergy X-ray absorptiometry ( DXA ) , both at baseline and after one year of treatment . Deoxypyridinoline ( DPD ) and bone-alkaline phosphatase ( B-ALP ) were determined at the beginning , mid study and at the end . RESULTS Patients treated only with calcium and cholecalciferol ( A1 , B1 subgroups ) showed a marked bone loss after 6 , and 12 months , with increased levels of DPD and BALP , compared to baseline values . Patients treated with neridronate ( A2 et B2 subgroups ) showed unchanged levels of these markers . After one year of treatment , lumbar and total hip BMD decreased significantly in patients treated only with calcium and cholecalciferol ( A1 subgroup : -4.9 % and -1.9 % respectively ) . BMD did not change significantly at any site in patients treated also with neridronate ( A2 subgroup : + 1 % and + 0.8 % respectively ) . Lumbar and total hip BMD did not change significantly ( -1.5 % and -1 % respectively ) in B1 subgroup . In B2 subgroup an important increase in lumbar spine and the total hip BMD was shown ( + 2.5 % and 1.6 % respectively ) . No relevant side effects were recorded during our study . CONCLUSION In conclusion , neridronate is an effective and safe treatment in preventing bone loss in men receiving ADT for prostate cancer PURPOSE We evaluate the relationship between the use of synthetic gonadotropin-releasing hormone ( Gn-RH ) agonists and bone loss in men . MATERIAL S AND METHODS Bone mineral density and parameters of mineral metabolism were evaluated in 12 patients with stage C prostatic carcinoma before and after 6 , 12 and 18 months of treatment with 3.75 mg . triptorelin intramuscularly every 4 weeks . RESULTS Of the 12 patients 9 were evaluated after 6 , 7 after 12 and 6 after 18 months of therapy . In comparison with month 0 , the lumbar and femoral neck bone mineral density tended to decrease at month 6 ( -3 and -2.7 % , p = 0.31 and 0.17 , respectively ) , at month 12 ( -4.6 and -3.9 % , p = 0.13 and 0.13 ) and at month 18 ( -7.1 and -6.6 % , p = 0.12 and 0.027 ) . A second analysis revealed that the lumbar and femoral neck bone mineral density was significantly decreased on the last evaluation compared to month 0 ( p = 0.05 and 0.028 , respectively ) . The serum osteocalcin was increased during treatment , suggesting an accelerated bone turnover in men treated with Gn-RH agonists . CONCLUSIONS The use of Gn-RH agonists in men may induce an accelerated bone loss . Further studies are needed to confirm these results and to evaluate the incidence of osteoporotic fractures in men treated with Gn-RH agonists OBJECTIVES To evaluate the effect of zoledronic acid on and rogen deprivation therapy in patients with hormone-sensitive prostate cancer by measuring the percentage change in lumbar-spine bone mineral density ( BMD ) at 12 and 24 months . MATERIAL S AND METHODS An open-label , multicenter , r and omized , two-phase study was conducted in patients with hormone-sensitive prostate cancer ( N = 200 ) receiving 10.8 mg goserelin acetate with or without zoledronic acid ( 4 mg intravenously ) every 3 months . In phase I , patients were r and omized to goserelin acetate alone or goserelin acetate plus zoledronic acid for 12 months . In phase II , patients receiving goserelin acetate plus zoledronic acid continued treatment for up to a total of 24 months , whereas patients receiving goserelin acetate alone were r and omized to goserelin acetate alone or goserelin acetate plus zoledronic acid for an additional 12 months . Lumbar-spine , femoral-neck , and total-hip BMD were assessed at 6 , 12 , and 24 months . Additional assessment s included height change , laboratory studies , bone scans , radiographs , and computed tomography scans . RESULTS Significant BMD differences between patients receiving goserelin acetate alone and goserelin acetate plus zoledronic acid were observed at the 12-month ( p < or= .01 for each site ) and 24-month ( p < .05 for each site ) assessment s. Initiating zoledronic acid after 12 months of goserelin acetate alone provided BMD benefits but was insufficient to completely restore BMD . Combining goserelin acetate and zoledronic acid was generally well tolerated . CONCLUSIONS Two years of zoledronic acid is well tolerated and can prevent bone loss in patients with prostate cancer undergoing and rogen deprivation therapy PURPOSE The aim of this study was to evaluate the efficacy and safety of zoledronic acid compared with placebo in preventing bone mineral density ( BMD ) loss and suppressing bone markers when initiated during the first year of and rogen deprivation therapy in patients with locally advanced prostate cancer . PATIENTS AND METHODS Patients were r and omized to receive zoledronic acid 4 mg or placebo intravenously every 3 months . Lumbar spine ( LS ) and total hip BMD was measured using dual-energy x-ray absorptiometry at baseline and at week 52 . N-telopeptide ( NTX ) and bone-specific alkaline phosphatase ( BSAP ) were evaluated at baseline and every 12 weeks . Safety assessment s were performed throughout the study . RESULTS Efficacy analyses included 106 patients and 109 patients in the zoledronic acid and placebo groups , respectively . At week 52 , the least squares mean BMD percentage differences were 6.7 % for LS and 3.7 % for total hip ( P < 0.0001 for both ) . In the zoledronic acid group , decreases in NTX ( (-)14 % to (-)28 % ) and BSAP ( (-)31 % to (-)37 % ) levels were significant and sustained ; changes in NTX levels and LS BMD ( r = (-)0.25 ; P = 0.04 ) and in BSAP levels and hip BMD ( r = (-)0.28 ; P = 0.02 ) were significantly correlated . Only traumatic fractures were reported for 2 and 3 patients receiving zoledronic acid and placebo , respectively . One patient in each group experienced acute renal failure . Osteonecrosis of the jaw was not reported . CONCLUSION Zoledronic acid ( 4 mg intravenously every 3 months ) was safe and effective in preventing bone loss and reducing bone turnover in patients with prostate cancer when initiated during the first year of and rogen deprivation therapy ; patients with low baseline BMD experienced the greatest benefit PURPOSE And rogen deprivation therapy in patients with prostate cancer is associated with bone loss and an increased risk of fractures . Zoledronic acid protects against bone mineral density loss when initiated concurrently with and rogen deprivation therapy . We evaluated the effect of zoledronic acid initiated subsequent to and rogen deprivation therapy on bone mineral density and biochemical markers of bone turnover . MATERIAL S AND METHODS Patients with prostate cancer without bone metastases who had received and rogen deprivation therapy for 12 months or less were r and omized to 4 mg zoledronic acid or placebo intravenously every 3 months for 1 year . Patients were stratified according to and rogen deprivation therapy duration ( less than 6 vs 6 to 12 months ) . The primary end point was the change in femoral neck and lumbar spine bone mineral density in the 2 groups . The secondary end point was the change in serum bone specific alkaline phosphatase and urine N-telopeptide levels . Total hip bone mineral density was also measured . RESULTS The 120 patients with prostate cancer received zoledronic acid ( 61 ) or placebo ( 59 ) . Compared with placebo , zoledronic acid increased femoral neck , total hip and lumbar spine bone mineral density yearly by 3.6 % ( p = 0.0004 ) , 3.8 % ( p < 0.0001 ) and 6.7 % ( p < 0.0001 ) , respectively . The effects of zoledronic acid on bone mineral density at these 3 sites were not differentiated according to and rogen deprivation therapy duration . Additionally , mean bone specific alkaline phosphatase and N-telopeptide levels were decreased in the zoledronic acid group ( each p < 0.0001 ) and were increased in the placebo group ( p < 0.0001 and p = 0.004 , respectively ) . CONCLUSIONS Zoledronic acid increased bone mineral density and suppressed bone turnover markers in patients with prostate cancer without bone metastases when initiated during year 1 of and rogen deprivation therapy PURPOSE In a recently completed 3-year , r and omized , double-blind study , denosumab , a fully human monoclonal antibody against receptor activator of nuclear factor kappaB lig and , significantly increased bone mineral density and decreased new vertebral fractures in men receiving and rogen deprivation therapy for prostate cancer . We conducted subgroup analyses to evaluate the relationships between subject characteristics and the effects of denosumab on bone mineral density at multiple skeletal sites . MATERIAL S AND METHODS A total of 1,468 subjects were r and omized 1:1 to receive 60 mg subcutaneous denosumab every 6 months or placebo for 36 months . In these analyses we evaluated the effects of denosumab on bone mineral density at the lumbar spine , total hip and distal 1/3 radius ( sub study of 309 subjects ) during 36 months in specific subgroups according to age , duration and type of prior and rogen deprivation therapy , bone mineral density T score , weight , body mass index , bone turnover marker levels and prevalent vertebral fractures . RESULTS After 36 months denosumab significantly increased bone mineral density of the lumbar spine , total hip and distal 1/3 radius by 7.9 % , 5.7 % and 6.9 % , respectively , compared with placebo ( p < 0.0001 for each comparison ) . Denosumab significantly increased bone mineral density to a degree similar to that observed in the overall analysis for every subgroup including older men as well as those with prevalent fractures , lower baseline bone mineral density , and higher serum C-telopeptide and tartrate-resistant alkaline phosphatase 5b . Mean increases in bone mineral density at each skeletal site were greatest for men with the highest levels of serum C-telopeptide and tartrate-resistant alkaline phosphatase 5b . CONCLUSIONS Denosumab significantly and consistently increased bone mineral density at all skeletal sites and in every subgroup , including men at greatest risk for bone loss and fractures |
751 | 20,577,121 | The effect was not lost on sensitivity analysis .
Subgroup analyses suggest greater effects in studies longer than 3 months , in Western population s , at lower doses , and in studies at lower risk of bias .
Soy isoflavone extracts significantly decreased SBP but not DBP in adult humans , and no dose-response relationship was observed . | OBJECTIVE Reported effects of different soy products on blood pressure vary .
This systematic review and meta- analysis was performed to clarify the effects of soy isoflavone extract supplements on systolic and diastolic blood pressure ( SBP and DBP ) in adult humans . | The objective of this study was to assess synergistic antioxidant properties of vitamin C and isoflavones . The design was a placebo-controlled crossover trial : 500 mg vitamin C , 5 mg/kg body weight isoflavones , 500 mg vitamin C plus 5 mg/kg body weight isoflavones , or placebo . Total lipid peroxides , plasma vitamin C , and blood pressure were measured . Eight of 10 healthy postmenopausal women completed the study . A multiple analysis of variance was performed and least-squares difference post-hoc test utilized to determine where differences occurred . Significance was defined as P < .05 . There was a significant reduction in total lipid peroxides between baseline and isoflavone treatments ( 3.22+/-0.72 vs 2.47+/-0.82 nmol/mL , P < .05 ) . Mean systolic blood pressure was higher during isoflavone intervention than placebo ( 117+/-14 vs 125+/-15 mm Hg , P= .042 ) . Supplementation with vitamin C and isoflavones did not produce a synergistic antioxidant effect . A slight but significant increase in systolic blood pressure occurred with isoflavone supplementation . A larger study should be conducted to fully explore the potential interactions between these antioxidants The objectives of the study were to clarify the relationship between blood pressure and mortality from stroke , heart disease , cardiovascular diseases and all causes of death among representative population of Japanese and to estimate category-specific excess mortality from stroke due to blood pressure ( BP ) level . The study design comprised a retrospective cohort study using the 1980 National Survey on Cardiovascular Diseases and identification of underlying causes of death using national vital statistics data . In 1994 , a 14-year follow-up cohort study was conducted among participants of the National Survey on Cardiovascular Diseases in 1980 , r and omly selected from the Japanese population . With a collaboration of 300 public health centres , which had conducted the original survey in 1980 , 91.4 % of the participants of the original survey could be followed up . Total observed person-years were 53 948 for men and 70 932 for women . During follow-up , 1327 deaths were observed . BP levels were significantly related to mortality from strokes , cardiovascular diseases and all causes of death for both sexes ( P<0.001 ) . Heart disease mortality was significantly related to BP levels among men ( P<0.05 ) while not among women . Estimated excess mortality was 130 % for men and 42 % for women and chiefly observed among moderate hypertensives ( 48 % for men and 16 % for women ) . In conclusion , high blood pressure was a risk factor for mortality from all causes as well as those from cardiovascular diseases , stroke and heart disease among Japanese . Since the major part of excess mortality was due to mild hypertension , a population strategy to reduce blood pressure should be encouraged BACKGROUND a small number of reports exist on the cognitive effects of soy isoflavones , the findings from which are mixed . Isoflavone efficacy is dependent upon conversion of glycosides contained in soy foods and supplements to the biologically active aglycons . Of particular interest is the production of the metabolite , equol , which is dependent upon intestinal microflora and an integrous digestive system , both being altered by age and age-associated conditions . Unfortunately , few studies enrolled adults over the age of 70 , and none included older men . OBJECTIVE we examined safety , feasibility and cognitive efficacy of soy isoflavone administration in older nondemented men and women ( age 62 - 89 years ) . DESIGN AND METHODS in this r and omised , placebo-controlled , double-blind pilot study , subjects ingested either 100 mg/day soy isoflavones ( glycoside weight ) or matching placebo tablets for 6 months . RESULTS active and placebo-treated subjects exhibited a comparable side-effect profile . Plasma levels of genistein and daidzein ( P < 0.001 ) , but not equol , increased with isoflavone administration . While similar at baseline , the two groups differed across 6 months of treatment on 8 of 11 cognitive tests administered . Isoflavone-treated subjects improved on tests of visual-spatial memory ( P < 0.01 ) and construction ( P = 0.01 ) , verbal fluency ( P < 0.01 ) and speeded dexterity ( P = 0.04 ) . Placebo-treated participants were faster than isoflavone-treated subjects on two tests of executive function ( P < 0.05 ) . CONCLUSIONS these data suggest that administration of 100 mg/day of isoflavones was well tolerated . Plasma genistein and daidzein levels , but not equol , increased with isoflavone administration . Finally , data support the potential cognitive effects of soy isoflavones in older adults BACKGROUND Soy foods contain several components ( isoflavones and amino acids ) that potentially affect bone . Few long-term , large clinical trials of soy as a means of improving bone mineral density ( BMD ) in late postmenopausal women have been conducted . OBJECTIVE Our goal was to evaluate the long-term effect of dietary soy protein and /or soy isoflavone consumption on skeletal health in late postmenopausal women . DESIGN We conducted a r and omized , double-blind , placebo-controlled clinical trial in 131 healthy ambulatory women aged > 60 y. Ninety-seven women completed the trial . After a 1-mo baseline period , subjects were r and omly assigned into 1 of 4 intervention groups : soy protein ( 18 g ) + isoflavone tablets ( 105 mg isoflavone aglycone equivalents ) , soy protein + placebo tablets , control protein + isoflavone tablets , and control protein + placebo tablets . RESULTS Consumption of protein powder and isoflavone pills did not differ between groups , and compliance with the study powder and pills was 80 - 90 % . No significant differences in BMD were observed between groups from baseline to 1 y after the intervention or in BMD change between equol and non-equol producers . However , there were significant negative correlations between total dietary protein ( per kg ) and markers of bone turnover ( P < 0.05 ) . CONCLUSIONS Because soy protein and isoflavones ( either alone or together ) did not affect BMD , they should not be considered as effective interventions for preserving skeletal health in older women . The negative correlation between dietary protein and bone turnover suggests that increasing protein intakes may suppress skeletal turnover . This trial was registered at Clinical Trials.gov as NCT00668447 OBJECTIVES It has been suggested that isoflavones protect the cardiovascular system , in part by improving lipid profile . The purpose of the present research was to examine the effect of a 12-week soy isoflavone supplementation on lipoprotein status and platelet thromboxane A2 receptor density . METHODS Twenty-nine healthy postmenopausal women were invited to take part in a r and omised study to receive either 100 mg/day isoflavone supplement ( n=15 ) or identical placebo capsules ( n=14 ) . Blood sample s obtained at baseline and after 12 weeks were analysed for isoflavones , total cholesterol , high density lipoprotein cholesterol , triglycerides , glucose , insulin , estradiol , testosterone , gonadotrophins , sex hormone-binding globulin ( SHBG ) and platelet thromboxane A2 receptor density . Blood pressure measurements , body mass index , subcutaneous fat at entrance and at the end of treatment were also registered . Changes in variables between groups were compared by ANOVA for repeated measures . RESULTS Blood pressure , body mass index , subcutaneous fat , insulin , serum lipoprotein , sex hormones and SHBG did not differ among groups . However , platelet thromboxane A2 receptor density declined significantly ( from 181.9+/-30.9 to 115.2+/-16.2 fmol/10(8 ) platelets ) in the experimental group , remaining mostly unchanged in the placebo group ( 176.3+/-27.3 to 170.4+/-28.2 fmol/10(8 ) platelets ) . The dissociation constant ( Kd ) values were unchanged . The change in platelet thromboxane A2 receptors correlated negatively with isoflavones serum concentration ( r=-0.59 , p<0.001 ) . CONCLUSIONS In this study we demonstrated that the beneficial effects of isoflavones in menopausal women could be more related to platelet function than to improving classical cardiovascular risk factors Background and Purpose We estimated the incidence of first-ever cerebral infa rct ion in regard to its subtypes and analyzed their risk factors separately in a community-based prospect i ve cohort study in Japan . Methods Stroke-free subjects ( n=1621 ) aged ≥40 years were followed up for 32 years from 1961 . During this period , 298 cerebral infa rct ions occurred and were divided into 167 lacunar , 62 atherothrombotic , 56 cardioembolic , and 13 undetermined subtypes of infa rct ion on the basis of clinical information including brain imaging and autopsy findings . Results The age-adjusted incidence of lacunar infa rct ion ( 3.8 per 1000 person-years for men and 2.0 for women ) was higher than that of atherothrombotic infa rct ion ( 1.2 , 0.7 ) and cardioembolic infa rct ion ( 1.3 , 0.5 ) in both sexes . Time-dependent Cox ’s proportional hazard analysis revealed systolic blood pressure as well as age to be independent risk factors for all subtypes of cerebral infa rct ion except for cardioembolic infa rct ion in men . Additionally , ST depression on ECG , glucose intolerance , and smoking in men and left ventricular hypertrophy on ECG and body mass index in women remained significant risk factors for lacunar infa rct ion . ST depression was also significantly related to events of atherothrombotic infa rct ion in women . The risk of atrial fibrillation for cardioembolic infa rct ion was outst and ingly high in both sexes , and left ventricular hypertrophy and lower total cholesterol were additional risk factors for cardioembolic infa rct ion in women . Conclusions In this Japanese population , lacunar infa rct ion was the most common subtype of cerebral infa rct ion and had a greater variety of risk factors , including not only hypertension but also ECG abnormalities , diabetes , obesity , and smoking , than did atherothrombotic infa rct ion or cardioembolic infa rct ion The phytoestrogen genistein improves endothelial dysfunction in ovariectomized rats through a nitric oxide-dependent mechanism . We investigated whether genistein alters the balance between the nitric oxide products and endothelin-1 and influences endothelium-dependent vasodilation in postmenopausal women . Sixty healthy postmenopausal women were enrolled in the study . A double-blind , placebo controlled , r and omized design was employed . After a 4-week stabilization on a st and ard fat-reduced diet , participants to the study were r and omly assigned to receive either genistein ( n=30 ; 54 mg/day ) or placebo ( n=30 ) . Flow-mediated , endothelium-dependent vasodilation of the brachial artery , plasma nitric oxide breakdown products and endothelin-1 levels were measured at baseline and after 6 months of genistein therapy . The mean baseline level of nitrites/nitrates was 22+/-10 micromol/l and increased to 41+/-10 micromol/ml after 6 months of treatment . The mean baseline plasma endothelin-1 level was 14+/-4 pg/ml and decreased to 7+/-1 pg/ml following 6 months of treatment with genistein . The mean baseline ratio of nitric oxide to endothelin also significantly increased at the end of treatment . Flow-mediated , endothelium-dependent vasodilation of the brachial artery was 3.9+/-0.8 mm at baseline and increased to 4.4+/-0.7 mm after 6 months of treatment . Placebo-treated women showed no changes in plasma nitrites/nitrates , endothelin-1 levels and flow-mediated vasodilation . Genistein therapy improves flow-mediated endothelium dependent vasodilation in healthy postmenopausal women . This improvement may be mediated by a direct effect of genistein on the vascular function and could be the result of an increased ratio of nitric oxide to endothelin OBJECTIVE To examine the change in menopausal symptoms and cardiovascular risk factors in response to 4 months of daily 100‐mg soy isoflavone in postmenopausal women . METHODS In this double‐blind , placebo‐controlled study , 80 women were r and omly assigned to isoflavone ( n = 40 ) and placebo ( n = 40 ) treatment . The menopausal Kupperman index was used to assess change in menopausal symptoms at baseline and after 4 months of treatment . Cardiovascular risk factors were assessed by evaluating plasma lipid levels , body mass index , blood pressure , and glucose levels in the participants . To examine the effects of this regime on endogenous hormone levels , follicle‐stimulating hormone ( FSH ) , luteinizing hormone ( LH ) , and 17β‐estradiol were measured . Transvaginal sonography was performed to quantify endometrial thickness . RESULTS The data showed a decrease in menopausal symptoms ( P < .01 , paired t test , two‐tailed , between baseline and isoflavone groups , and P < .01 , unpaired t test , between placebo and isoflavone groups ) . Total cholesterol and low‐density lipoprotein decreased significantly in the isoflavone group compared with the baseline or placebo group ( P < .001 , paired t test , two‐tailed , between baseline and isoflavone groups , and P < .01 , unpaired t test , between placebo and isoflavone groups ) . The isoflavone treatment appeared to have no effect on blood pressure , plasma glucose , and high‐density lipoprotein and triglyceride levels . CONCLUSION This study suggests that isoflavone 100‐mg regime treatment may be a safe and effective alternative therapy for menopausal symptoms and may offer a benefit to the cardiovascular system OBJECTIVE To compare the effects of raloxifene , estradiol valerate plus dienogest , and soy isoflavones ( genistein ) on serum concentrations of high-sensitive C-reactive protein in healthy postmenopausal women . METHODS The 80 healthy postmenopausal women enrolled in the study were r and omly allocated to receive 60 mg of raloxifene , 2 mg of estradiol valerate plus dienogest , 40 mg of genistein , or placebo ( n=20 in each group ) . Blood sample s were collected at the start of the study and at 3 and 6 months . Lipid profile was also determined . RESULTS Only the group receiving estradiol valerate plus dienogest showed an increase in serum levels of high-sensitive C-reactive protein compared with baseline values and values in the control and other groups . All 3 treatments result ed in an increase in high-density lipoprotein cholesterol levels and a decrease in total , low-density , and very-low-density lipoprotein cholesterol levels . CONCLUSIONS Estradiol valerate plus dienogest , but not raloxifene and genistein , increase serum high-sensitive C-reactive protein levels . All 3 treatments , however , have an estrogen-like effect on serum lipid profile Plant estrogen or phytoestrogens ( PE ) are increasingly consumed for the purpose s of menopause symptom relief and prevention of cardiovascular and other diseases . The objective of this study was to evaluate the effects of PE on plasma lipids and lipoproteins and on endothelial function . Twenty healthy , postmenopausal women , 50 to 70 years old , and with evidence of endothelial dysfunction , were treated with a soybean PE tablet of 80 mg/day of isoflavones . Endothelial function was assessed noninvasively using brachial ultrasound . A double-blind , placebo-controlled , r and omized crossover design was employed . After 3 weeks stabilization on a st and ard fat-reduced diet , subjects received PE or placebo for 8 weeks in r and om order , separated by a washout period of 8 weeks . Compared with placebo , there were no significant effects of PE on blood pressure and plasma lipid or lipoprotein concentrations . Flow-mediated endothelium-dependent dilation ( FMD ) in response to reactive hyperemia was not significantly changed by PE ingestion ( 3 . 3 + /- 0.7 % on placebo vs 4.1 + /- 0.7 % on PE , p > 0.4 ) . Variation in FMD was not correlated with change in plasma isoflavone concentration ( r = -0.09 , p > 0.7 ) . Glyceryl trinitrate endothelium-independent dilation was not significantly changed with PE ( 15.9 + /- 1.3 % vs 13.7 + /- 1.2 % , p > 0.1 ) . These results fail to show a significant impact of medium-term supplementation with 80 mg/day of isoflavones on lipid and lipoprotein levels or on endothelial function in healthy , postmenopausal women Objective : The aim of this study was to determine the effect of DRIs on hot flash symptoms in menopausal women . Design : This was a r and omized , double-blind , placebo-controlled trial of menopausal women , aged 38 to 60 years , who experienced 4 to 14 hot flashes per day . After a 1-week run-in period , a total of 190 menopausal women were r and omized to receive a placebo or 40 or 60 mg/day of a DRI for 12 weeks . The primary outcome was the mean changes from baseline to week 12 in the frequency of hot flashes recorded in the participant diary . The secondary outcomes included changes in quality of life and hormonal profiles . Results : A total of 147 women ( 77 % ) completed the study . It was found that 40 and 60 mg of DRI improved hot flash frequency and severity equally . At 8 weeks hot flash frequency was reduced by 43 % in the 40-mg DRI group and by 41 % in the 60-mg DRI group , compared with 32 % in the placebo group ( P = not significant vs placebo ) . The corresponding numbers for 12 weeks were 52 % , 51 % , and 39 % , respectively ( P = 0.07 and 0.09 vs placebo ) . When comparing the two treatment groups with the placebo group , there were significant reductions in mean daily hot flash frequency . The supplement ( either 40 or 60 mg ) reduced hot flash frequency by 43 % at 8 weeks ( P = 0.1 ) and 52 % at 12 weeks ( P = 0.048 ) but did not cause any significant changes in endogenous sex hormones or thyroid hormones . Menopausal quality of life improved in all three groups , although there were no statistically significant differences between groups . Conclusions : DRI supplementation may be an effective and acceptable alternative to hormone treatment for menopausal hot flashes UNLABELLED The combined intervention of isoflavone intake and walking exercise over 1 year in postmenopausal Japanese women exhibited a trend for a greater effect on prevention of bone loss at the total hip and Ward 's triangle regions . INTRODUCTION The additive effects of isoflavones and exercise on bone and lipid metabolism have been shown in estrogen-deficient animals . In this study , we determined the effects of isoflavone intake , walking exercise , and their interaction on bone , fat mass , and lipid metabolism over 1 year in postmenopausal Japanese women . MATERIAL S AND METHODS A total of 136 postmenopausal women at < 5 years after the onset of menopause were r and omly assigned to four groups : ( 1 ) placebo , ( 2 ) walking ( 45 minutes/day , 3 days/week ) with placebo , ( 3 ) isoflavone intake ( 75 mg of isoflavone conjugates/day ) , and ( 4 ) combination of isoflavone plus walking . BMD , fat mass , serum lipid , and serum and urinary isoflavone concentrations were assessed . RESULTS A significant main effect of isoflavone on the reduction in trunk fat mass was obtained at 12 months . Significant main effects of walking on the reduction in fat mass in the whole body and the trunk were observed at 3 , 6 , and 12 months and that in the legs and arms at 6 and 12 months . Serum high-density lipoprotein (HDL)-cholesterol concentration significantly increased by 12 months after the walking and the combined intervention . After 12 months , a significant main effect of isoflavone on BMD was observed only at Ward 's triangle . Walking prevented bone loss at the total hip and the Ward 's triangle to significant degrees . The effect of the combined intervention on BMD at total hip and Ward 's triangle regions was greater than that of either alone . No significant interaction was observed between isoflavone and walking in any measurements recorded during the study . CONCLUSIONS Our study suggest that combined intervention of 75 mg/day of isoflavone intake and walking exercise 3 times/week for 1 year showed a trend for a greater effect on BMD at total hip and Ward 's triangle regions than either alone . Intervention with isoflavone in postmenopausal Japanese women showed a modest effect on BMD compared with those in Westerners . Further studies over longer treatment duration that include assessment of BMD at various regions are necessary to ascertain the clinical significance of the combined intervention of isoflavone plus walking in postmenopausal women Background Genistein , a phytoestrogen , may have estrogenic cardioprotective actions . We investigated whether genistein influences endothelium-dependent vasodilation in forearm vasculature of healthy human subjects and compared the effects of genistein with those of 17&bgr;-estradiol . Methods and Results The brachial arterial was cannulated with a 27-gauge needle for drug infusion . Forearm blood flow responses were measured with strain-gauge plethysmography . Genistein ( 10 to 300 nmol/min , each dose for 6 minutes ) produced a dose-dependent increase in forearm blood flow from 3.4±0.3 to 9.6±1.3 mL · min−1 · 100 mL forearm−1 ( mean±SEM ) in men ( n=9 , P < 0.0001 by ANOVA ) . The mean forearm venous concentration of genistein during infusion of the highest dose was 1.8±0.3 & mgr;mol/L in 6 additional men . Genistein produced a similar increase in blood flow in premenopausal women . Daidzein , another phytoestrogen , was ineffective , but equimolar concentrations of 17&bgr;-estradiol caused similar vasodilation to genistein . Responses to genistein and 17&bgr;-estradiol were inhibited to the same degree by the NO synthase inhibitor NG-monomethyl-l-arginine . A threshold dose of genistein potentiated the endothelium-dependent vasodilator acetylcholine but not the endothelium-independent vasodilator nitroprusside . Conclusions Genistein causes l-arginine/NO-dependent vasodilation in forearm vasculature of human subjects with similar potency to 17&bgr;-estradiol and potentiates endothelium-dependent vasodilation to acetylcholine Postmenopausal women have more severe endothelial dysfunction than premenopausal women . In the present study , we evaluated the possible beneficial effect of raloxifene administration , a selective estrogen receptor modulator , on endothelial regulation in postmenopausal women . In a double-blind , r and omized vs. placebo trial , 60 healthy postmenopausal women were treated with raloxifene ( 60 mg/d ) or placebo for 4 months to evaluate the effect of raloxifene treatment on endothelial function . Furthermore , in raloxifene-treated subjects ( n = 30 ) , the effect of raloxifene was also assessed during the intraarterial infusion of N(G)-monomethyl-L-arginine ( 4 micromol/min ) . Raloxifene administration vs. placebo was associated with a decrease in plasma low-density lipoprotein cholesterol ( P < 0.01 ) , triglyceride ( P < 0.05 ) , thiobarbituric acid-reactive substance ( P < 0.01 ) , vascular cell adhesion molecule-1 ( P < 0.05 ) , intercellular adhesion molecule-1 ( P < 0.001 ) , and E-selectin ( P < 0.001 ) levels and with an increase in plasma Trolox equivalent antioxidant capacity ( P < 0.001 ) levels . Indeed , raloxifene treatment was also associated with a significant improvement in endothelial-dependent vasodilatation assessed by brachial reactivity technique . Raloxifene administration had no impact on endothelial-independent vasodilatation . Furthermore , intraarterial infusion of N(G)-monomethyl-L-arginine inhibited the significant effect of raloxifene on endothelium-mediated brachial arterial diameter and flow . In conclusion , our results demonstrate that raloxifene administration is associated with a positive modulation of endothelial-dependent vasodilatation likely due to a reduction of risk factors for endothelial damage Objective To compare the effects of raloxifene and soy phytoestrogens on endothelial function in healthy , postmenopausal women . Design R and omized , double-blind , placebo-controlled , cross-over trial . Subjects ( n = 22 ; mean age 58.5 years ) underwent endothelial function testing at baseline and following 6 weeks of daily raloxifene 60 mg , soy phytoestrogens 55 mg , and placebo in r and om sequence with intervening 6-week wash-out periods . Endothelial function was assessed as flow-mediated vasodilatation ( FMD ) of the brachial artery using high-resolution ultrasound ; digital flux was measured with laser Doppler velocimetry . Results Baseline ( pretreatment ) FMD was almost within normal range at 9.6 % ( ±6.4 ) . FMD did not change from baseline within any treatment group , and no between-group differences were detected . FMD values following treatment with raloxifene , soy , and placebo were 10.3 % ( ±12.3 ) , 8.3 % ( ±7.7 ) , and 9.5 % ( ±4.4 ) , respectively . Area under curve ratios showed no treatment differences for digital velocimetry . Conclusions In this study , neither raloxifene nor soy enhanced endothelial function in postmenopausal women . However , the cohort had relatively normal endothelial function at baseline . Further study is required to determine if particular subgroups of postmenopausal women derive vascular benefit from the use of selective estrogen receptor modulators or soy phytoestrogens Objective : To evaluate the effects of soy isoflavone administration on endothelial function in healthy postmenopausal women . Design : Sixty naturally postmenopausal women were r and omly assigned to receive isoflavone or placebo tablets for 6 months . Endothelium-dependent vasodilatation was measured by brachial reactivity technique along with levels of plasma soluble intercellular adhesion molecule-1 ( ICAM-1 ) , vascular cell adhesion molecule-1 ( VCAM-1 ) , E-selectin , P-selectin and soluble thrombomodulin , von Willebr and factor , and tissue plasminogen activator . Differences between endothelium-dependent and endothelium-independent vasodilatation were assessed by evaluating brachial reactivity parameters after reactive hyperemia and after sublingual administration of nitroglycerin ; furthermore , in the active group , the effect of isoflavones was also evaluated during the intra-arterial infusion of NG-monomethyl-L-arginine . Serum levels of lipids [ high-density lipoprotein and low-density lipoprotein cholesterol , triglycerides and lipoprotein(a ) ] and hemostatic factors ( prothrombin , fibrinogen , plasminogen activator inhibitor-1 , and fibrin D-dimer ) were also measured . To confirm the absorption of isoflavones , their blood concentrations were determined . Results : Isoflavone treatment versus placebo was associated with a significant improvement in endothelium-dependent vasodilatation but had no impact on endothelial-independent arterial diameter and flow . Intra-arterial infusion of NG-monomethyl-L-arginine inhibited the significant effect of isoflavones on endothelium-mediated vasodilatation . Furthermore , isoflavone group experienced statistically significant reductions in plasma concentrations of ICAM-1 , VCAM-1 , and E-selectin . Levels of soluble thrombomodulin , von Willebr and factor , tissue plasminogen activator , lipids , and hemostatic factors did not change significantly throughout the study in both groups . Conclusions : Our findings suggest a positive influence of soy isoflavones on endothelial function in healthy postmenopausal women as evidence d by an improvement in endothelium-dependent vasodilatation and a reduction in plasma adhesion molecule levels |
752 | 30,122,240 | RESULT Extracted data for Seven systematic review s for primary outcomes , net changes in cardiac output , cardiac index , New York Heart Association functional classification , improved survival , based on existing evidence , there is a case for use of CoQ10 as an adjunctive therapy in congestive heart failure , especially in those patients unable to tolerate mainstream medical therapies .
Evidence suggests that the CoQ10 supplement may be a useful tool for managing patients with heart failure | INTRODUCTION This article is an attempt to provide an overview of systematic review s to determine the efficacy of CQ10 supplementation in the treatment of patients with cardiovascular diseases ( CVD ) . | The objective of this study was to assess the effect of coenzyme Q10 ( CoQ10 ) as supplementation to conventional antifailure drugs on quality of life and cardiac function in children with chronic heart failure due to dilated cardiomyopathy ( DCM ) . The study was an open-label prospect i ve study performed in two of the largest pediatric centers in Thail and from August 2000 to June 2003 . A total of 15 patients with idiopathic chronic DCM were included , with the median age of 4.4 years ( range , 0.6 - 16.3 ) . Presenting symptoms were congestive heart failure in 12 cases ( 80 % ) , cardiogenic shock in 2 cases ( 13.3 % ) , and cardiac arrhythmia in 1 case ( 6.7 % ) . Sixty-one percent of patients were in the New York Heart Association functional class 2 ( NYHA 2 ) , 31 % in NYHA 3 , and 8 % in NYHA 4 . Cardiothoracic ratio from chest x-ray , left ventricular ejection fraction , and left ventricular end diastolic dimension in echocardiogram were 0.62 ( range , 0.55 - 0.78 ) , 30 % ( range , 20 - 40 ) , and 5.2 cm ( range , 3.8 - 6.5 ) , respectively . CoQ10 was given at a dosage of 3.1 ? 0.6 mg/kg/day for 9 months as a supplementation to a fixed amount of conventional antifailure drugs throughout the study . At follow-up periods of 1 , 3 , 6 , and 9 months , NYHA functional class was significantly improved , as was CT ratio and QRS duration at 3 and 9 months follow-up with CoQ10 when compared to the baseline and post-discontinuation of CoQ10 at 9 months ( range , 4.8 - 10.8 ) . However , when multiple comparisons were taken into consideration , there was no statistical significant improvement . In addition to the conventional antifailure drugs , CoQ10 may improve NYHA class and CT ratio and shorten ventricular depolarization in children with chronic idiopathic DCM BACKGROUND The number of patients awaiting heart transplantation is increasing in proportion to the waiting period for a donor . Studies have shown that coenzyme Q10 ( CoQ10 ) has a beneficial effect on patients with heart failure . HYPOTHESIS The purpose of the present double-blind , placebo-controlled , r and omized study was to assess the effect of CoQ10 on patients with end-stage heart failure and to determine if CoQ10 can improve the pharmacological bridge to heart transplantation . METHODS A prospect i ve double-blind design was used . Thirty-two patients with end-stage heart failure awaiting heart transplantation were r and omly allocated to receive either 60 mg U/day of Ultrasome -- CoQ10 ( special preparation to increase intestinal absorption ) or placebo for 3 months . All patients continued their regular medication regimen . Assessment s included anamnesis with an extended question naire based partially on the Minnesota Living with Heart Failure Question naire , 6-min walk test , blood tests for atrial natriuretic factor ( ANF ) and tumor necrosis factor ( TNF ) , and echocardiography . RESULTS Twenty-seven patients completed the study . The study group showed significant improvement in the 6-min walk test and a decrease in dyspnea , New York Heart Association ( NYHA ) classification , nocturia , and fatigue . No significant changes were noted after 3 months of treatment in echocardiography parameters ( dimensions and contractility of cardiac chambers ) or ANF and TNF blood levels . CONCLUSIONS The administration of CoQ10 to heart transplant c and i date s led to a significant improvement in functional status , clinical symptoms , and quality of life . However , there were no objective changes in echo measurements or ANF and TNF blood levels . Coenzyme Q10 may serve as an optional addition to the pharmacologic armamentarium of patients with end-stage heart failure . The apparent discrepancy between significant clinical improvement and unchanged cardiac status requires further investigation Despite major advances in treatment congestive heart failure ( CHF ) is still one of the major causes of morbidity and mortality . Coenzyme Q10 is a naturally occurring substance that has antioxidant and membrane stabilizing properties . Administration of coenzyme Q10 in conjunction with st and ard medical therapy has been reported to augment myocardial kinetics , increase cardiac output , elevate the ischemic threshold , and enhance functional capacity in patients with congestive heart failure . The aim of this study was to investigate some of these cl aims . Seventeen patients ( mean New York Heart Association functional class 3.0 ± 0.4 ) were enrolled in an open-label study . After 4 months of coenzyme Q10 , therapy , functional class improved 20 % ( 3.0 ± 0.4 to 2.4 ± 0.6 , p < 0.001 ) and there was a 27 % improvement in mean CHF score ( 2.8 ± 0.4 to 2.2 ± 0.4 , p < 0.001 ) . Percent change in the resting variables included the following : left ventricular ejection fraction ( LVEF ) , + 34.8 % ; cardiac output , + 15.7 % ; stroke volume index , + 18.9 % ; end-diastolic volume area , −8.4 % ; systolic blood pressure ( SBP ) , −4.4 % ; and Emax , ( SBP end-systolic volume index [ ESVI ] ) + 11.7 % . MVo2 decreased by 5.3 % ( 31.9 ± 2.6 to 30.2 ± 2.4 , p = NS ) . Therapy with coenzyme Q10 was associated with a mean 25.4 % increase in exercise duration and a 14.3 % increase in workload . Percent changes after therapy include the following : exercise LVEF , + 24.6 % ; cardiac output , + 19.1 % ; stroke volume index , + 13.2 % ; heart rate , + 6.5 % ; SBP , −4.3 % ; SBP ESVI , + 18.6 % ; end-diastolic volume ( EDV ) area , −6.0 % ; MVo2 , −7.0 % ; and ventricular compliance ( % δ SV EDV ) improved < 100 % . In summary , coenzyme Q10 therapy is associated with significant functional , clinical , and hemodynamic improvements within the context of an extremely favorable benefit-to-risk ratio . Coenzyme Q10 enhances cardiac output by exerting a positive inotropic effect upon the myocardium as well as mild vasodilatation The long-term efficacy and safety of HMG-CoA reductase inhibitors ( statins ) have been established in large multicenter trials . Inhibition of this enzyme , however , results in decreased synthesis of cholesterol and other products downstream of mevalonate , such as CoQ10 or dolichol . This was a r and omized double-blind , placebo-controlled study that examined the effects of CoQ10 and placebo in hypercholesterolemic patients treated by atorvastatin . Eligible patients were given 10mg/day of atorvastatin for 16 weeks . Half of the patients ( n=24 ) were supplemented with 100mg/day of CoQ10 , while the other half ( n=25 ) were given the placebo . Serum LDL-C levels in the CoQ10 group decreased by 43 % , while in the placebo group by 49 % . The HDL-C increment was more striking in the CoQ10 group than in the placebo group . All patients showed definite reductions of plasma CoQ10 levels in the placebo group , by 42 % . All patients supplemented with CoQ10 showed striking increases in plasma CoQ10 by 127 % . In conclusion atorvastatin definitely decreased plasma CoQ10 levels and supplementation with CoQ10 increased their levels . These changes in plasma CoQ10 levels showed no relation to the changes in serum AST , ALT and CK levels . Further studies are needed , however , for the evaluation of CoQ10 supplementation in statin therapy OBJECTIVES The aim of this study was to evaluate the relationship between plasma oxidized low-density lipoprotein ( oxLDL ) , a marker of oxidative stress , and the prognosis of patients with chronic congestive heart failure ( CHF ) . BACKGROUND Oxidative stress appears to play a role in the pathophysiology of CHF . We have recently reported the usefulness of plasma oxLDL as a marker of oxidative stress in CHF patients with dilated cardiomyopathy . METHODS We measured the plasma level of oxLDL by s and wich enzyme-linked immunosorbent assay using a specific monoclonal antibody against oxLDL in 18 age-matched normal subjects and in 84 patients with chronic CHF ( New York Heart Association functional class II to IV ) and monitored them prospect ively for a mean follow-up period of 780 days . RESULTS Plasma oxLDL level was significantly higher in severe CHF patients than in control subjects and mild CHF patients . A significant negative correlation existed between the plasma level of oxLDL and left ventricular ejection fraction ( LVEF ) and a significant positive correlation between the plasma level of oxLDL and plasma norepinephrine level . Twenty-six patients had cardiac events ; 14 had cardiac death and 12 were hospitalized for heart failure or other cardiovascular events . Among 10 variables including LVEF and neurohumoral factors , only high plasma levels of brain natriuretic peptide and oxLDL were shown to be independent predictors of mortality . CONCLUSIONS These results indicate that the plasma level of oxLDL is a useful predictor of mortality in patients with CHF , suggesting that oxidative stress plays an important role in the pathophysiology of CHF There are numerous reasons to believe that deficiency of coenzyme Q10 ( ubiquinone ) may exacerbate the poor contractility of myocardial cells in patients with heart failure . Not only does coenzyme Q10 play a central role in mitochondrial oxidative phosphorylation ( 1 ) , but it may also act as an antioxidant scavenger ( 2 ) . Because the myocardium of patients with congestive heart failure demonstrates oxidative stress ( 3 ) and coenzyme Q10 prevents lipid peroxidation ( 4 ) , this substance conceivably could prevent myocardial destruction . Furthermore , the concentration of coenzyme Q10 is decreased in myocardial cells of patients with advanced heart failure ( 5 ) , and the extent of myocardial coenzyme Q10 deficiency correlates with the clinical severity of heart failure ( 5 , 6 ) . It is thus not surprising that nutritional supplementation with coenzyme Q10 has been proposed as a treatment for congestive heart failure , that it is extensively advertised , and that it is commonly used by patients with this condition . Many small studies have been published , but most were uncontrolled and unblinded . Approximately 31 Japanese clinical reports describe favorable effects with intravenous or oral coenzyme Q10 ( 7 ) . The studies involved only a small number of patients with heart failure and tended to include patients with cardiac disease of various causes . Nevertheless , in 1974 the Japanese government approved marketing of coenzyme Q10 for the treatment of heart failure . The few U.S. and European studies have had conflicting results . Some controlled studies showed no effect ( 8 , 9 ) , but their limitations make the results inconclusive . Other trials noted improvement ( 10 - 13 ) , but concerns about end points , small numbers of patients , and the lack of blinding have limited the acceptance of these studies . With such conflicting data , r and omized , controlled , and blinded studies are needed to test the hypothesis that patients with advanced heart failure are deficient in coenzyme Q10 and that oral supplementation with coenzyme Q10 results in clinical improvement . We therefore evaluated the effects of coenzyme Q10 supplementation on left ventricular ejection fraction and exercise tolerance in patients with symptomatic heart failure despite st and ard medical therapy . Methods We performed a r and omized , double-blind , placebo-controlled trial to compare the effects of oral coenzyme Q10 ( 200 mg/d ) and placebo . The two primary end points were change in ejection fraction , as assessed by nuclear ventriculography , and change in peak oxygen consumption . The study protocol was approved by the human volunteers committee of the University of Maryl and School of Medicine . Inclusion and Exclusion Criteria Patients with New York Heart Association functional class III or IV disease were eligible for inclusion in this study . All patients had ejection fractions less than 40 % ( documented by radionuclide ventriculography ) and maximal oxygen consumption less than 17.0 mL/kg of body weight per minute or less than 50 % of the predicted value . These criteria were used to select symptomatic patients who would have the potential to improve . The mean peak oxygen consumption in our patients was 13.1 mL/kg per minute . In comparison , the peak oxygen consumption criterion for cardiac transplantation is generally considered to be less than 14.0 mL/kg per minute , and the mean peak oxygen consumption in nonexercising normal elderly persons ( mean age , 67 years ) has been reported to be 19.0 mL/kg per minute ( 14 ) . Patients were required to have been receiving an unchanged medical regimen for at least 1 month . Patients who had previously taken coenzyme Q10 were excluded . Baseline Testing At baseline , three procedures were performed . First , a grade d symptom-limited cardiopulmonary exercise test using the Naughton protocol was conducted to assess maximal oxygen consumption . The test was performed by the same operator and was repeated until the maximum oxygen consumption measures on two consecutive test results were within 15 % of each other . The final test was considered to be the baseline test with which to assess change during therapy . Second , radionuclide ventriculography was performed by using st and ard techniques . Third , serum concentration of coenzyme Q10 was measured as described elsewhere ( 15 ) . Three patients did not have concentrations obtained at baseline or follow-up . Intervention Patients were r and omly assigned to receive 200 mg of coenzyme Q10 per day or placebo . R and omization was performed by using a r and om-number generator . All patients and study personnel were blinded to study group assignment until all data were final . The dosage was chosen to minimize the chance of inadequate treatment . Previous studies reporting benefit with coenzyme Q10 supplementation have generally used daily dosages of 100 or 150 mg ( 6 , 7 , 9 - 13 , 16 - 18 ) . Final Assessment After 6 months , all baseline procedures were repeated . At that time , patients were asked whether their symptoms were improved , worse , or the same . Statistical Analysis The change in values of primary and secondary end points were compared by using an unpaired Student t-test . All values are given as the mean SD . For significance , a P value less than 0.05 was required . The study was planned to have 80 % power to detect a difference of 2.8 mL/kg per minute in the peak oxygen consumption , with a P value of 0.05 . This assumed a mean oxygen consumption of 13.0 4.0 mL/kg per minute . We used StatMost , version 3.5 ( Data xiom Software , Inc. , Los Angeles , California ) , for all statistical analyses . Results Fifty-five patients were r and omly assigned . Nine patients did not finish the study : 5 in the coenzyme Q10 group and 4 in the placebo group . One patient ( who was r and omly assigned to receive coenzyme Q10 ) was withdrawn from the study before repeated assessment s and unblinding because of error in enrollment criteria . Three patients died : One patient assigned to the placebo group died of progressive heart failure , and 2 patients assigned to the coenzyme Q10 group died of myocardial infa rct ion and sudden death , respectively . Four patients did not complete the study because of conditions that prevented them from exercising ( esophageal cancer , uncontrolled ventricular tachycardia , foot amputation , and pulmonary edema ) . One patient r and omly assigned to receive coenzyme Q10 withdrew from the study . Baseline characteristics did not differ between the two groups . Twenty-three patients in each group completed the study . The study sample consisted of 39 men and 7 women , and the mean age in both groups was 64 years . Twenty-seven patients had known ischemic heart disease . Forty-two patients were categorized as being in New York Heart Association class III and 4 were in class IV . All patients were receiving digoxin and angiotensin-converting enzyme inhibitors or other vasodilators . Eighteen patients in each group were receiving -blockers , and 22 patients in each group were receiving diuretics . No adverse reactions were attributed to the study drug , and no gastrointestinal side effects occurred . Maximal Oxygen Consumption After 6 months of blinded therapy , maximal oxygen consumption did not improve in the placebo or coenzyme Q10 group ( Figure 1 ) . Maximal oxygen consumption increased by 0.21 3.4 mL/kg per minute ( 95 % CI , 1.25 to 1.68 mL/kg per minute ) in the patients who received coenzyme Q10 and decreased by 0.49 2.4 mL/kg per minute ( CI , 1.54 to 0.55 mL/kg per minute ) in the patients who received placebo . The difference between groups was not significant . The respiratory quotient was 1.01 0.07 at baseline and 0.99 0.07 after treatment . Exercise duration did not change significantly in either group . In the coenzyme Q10 recipients , mean exercise duration was 8.5 3.2 minutes before treatment and 9.1 3.4 minutes after treatment . In the placebo recipients , exercise duration was 7.7 3.2 minutes before treatment and 7.5 2.9 minutes after 6 months . Figure 1 . Ejection fraction and peak oxygen consumption before and after the treatment period for each patient who received placebo ( left ) and coenzyme Q ( right ) . Radionuclide Ventriculography Coenzyme Q10 had no effect on left ventricular ejection fraction ( Figure 2 ) . Ejection fraction decreased minimally ( 0.3 8 percentage points [ CI , 3.7 to 3.1 percentage points ] ) in the patients who received coenzyme Q10 and decreased by 0.2 8.6 percentage points ( CI , 4.0 to 3.6 percentage points ) in the patients who received placebo . Mean left ventricular ejection fraction was 27 % before and after treatment in the patients who received coenzyme Q10 and was 30 % before and after treatment in the patients who received placebo . Right ventricular ejection fraction decreased from 39 % 14 % to 37 % 8 % in the placebo group . In patients receiving coenzyme Q10 , right ventricular ejection fraction was 35 % 13 % before treatment and 35 % 11 % after 6 months . Figure 2 . The change in coenzyme Q concentration compared with the change in peak oxygen consumption . Symptoms One patient in each group had improved symptoms , as indicated by New York Heart Association classification . Almost three quarters of the patients classified themselves as neither improved nor worse after 6 months of treatment ( 18 patients receiving placebo and 16 patients receiving coenzyme Q10 ) . Six patients in the coenzyme Q10 group believed that their symptoms had improved even minimally , and one patient believed that symptoms had deteriorated . Two patients in the placebo group reported improvement in symptoms and 3 patients reported increased severity of symptoms . Coenzyme Q10 Serum Concentrations Before r and omization , coenzyme Q10 serum concentrations were similar in both groups . With treatment , concentrations increased in the intervention group from 0.95 0.62 g/mL to 2.2 1.2 g/mL ; in the placebo group , concentrations did not change ( 0.92 0.34 g/mL before treatment and 0.96 0.45 g/mL after 6 months ) . The difference between groups was highly significant ( P<0.001 ) . Among patients who We aim ed to determine the effect of supplementation with coenzyme Q10 on conventional therapy of children with cardiac failure due to idiopathic dilated cardiomyopathy . In a prospect i ve , r and omized , double-blinded , placebo-controlled trial , we r and omized 38 patients younger than 18 years with idiopathic dilated cardiomyopathy to receive either coenzyme Q10 , chosen for 17 patients , or placebo , administered in the remaining 21 . Echocardiographic systolic and diastolic function parameters were determined for every patient at baseline , and after 6 months of supplementation . The index score for cardiac failure in children as established in New York was used for assessing the functional class of the patients . After 6 months supplementation , 10 patients r and omized to receive coenzyme Q10 showed improvements in the grading of diastolic function , this being significantly more than that achieved by those r and omized to the placebo group ( p value = 0.011 ) . The mean score for the index of cardiac failure index for those receiving coenzyme Q10 was also lower than the control group ( p value = 0.024).Our results , therefore , indicate that administration of coenzyme Q10 is useful in ameliorating cardiac failure in patients with idiopathic dilated cardiomyopathy through its significant effect on improving diastolic function A r and omized , prospect i ve study of the effectiveness of preoperative administration of coenzyme Q10 on the prophylaxis of postoperative low cardiac output state was performed in 50 patients with acquired valvular diseases necessitating valve replacement . There were 25 patients in the treatment group and 25 in the control group . Patients in the treatment group received 30 to 60 mg of coenzyme Q10 orally for six days before operation . Preoperative clinical variables , operative procedures , total cardiopulmonary bypass time , and aortic cross-clamping time were similar for the two groups . Postoperatively , mild to severe low cardiac output state developed in 28 of 50 patients ( 56 % ) and necessitated the administration of considerable amounts of inotropic agent . The treatment group showed a significantly lower incidence of low cardiac output state during the recovery period than the control group ( p less than 0.05 ) . These results suggest that preoperative administration of coenzyme Q10 will increase the tolerance of human hearts to ischemia during aortic cross-clamping Nineteen patients with chronic myocardial disease ( NYHA Classes III and IV ) were given Coenzyme Q10 in a controlled double-blind cross-over study . All had either low or borderline levels of CoQ10 in their blood , and showed a significant change into the normal range with oral CoQ10 replacement . Eighteen patients reported improvement in activity tolerance with replacement therapy . Combined clinical observations , stroke volume measured by impedance cardiography , and ejection fractions calculated from systolic time intervals , all showed significant improvement in parallel with CoQ10 administration . This application of the principles of bioenergetics introduces a promising new dimension to the study and treatment of the complex problem of myocardial failure |
753 | 30,575,845 | Conclusions and Relevance The findings suggest that administration of corticosteroids is associated with reduced 28-day mortality compared with placebo use or st and ard supportive care . | Importance Although corticosteroids are widely used for adults with sepsis , both the overall benefit and potential risks remain unclear .
Objective To conduct a systematic review and meta- analysis of the efficacy and safety of corticosteroids in patients with sepsis . | CONTEXT AND OBJECTIVE Sepsis and septic shock are very common conditions among critically ill patients that lead to multiple organ dysfunction syndrome ( MODS ) and death . Our purpose was to investigate the efficacy of early administration of dexamethasone for patients with septic shock , with the aim of halting the progression towards MODS and death . DESIGN AND SETTING Prospect i ve , r and omized , double-blind , single-center study , developed in a surgical intensive care unit at Hospital das Clínicas , Faculdade de Medicina da Universidade de São Paulo . METHODS The study involved 29 patients with septic shock . All eligible patients were prospect ively r and omized to receive either a dose of 0.2 mg/kg of dexamethasone ( group D ) or placebo ( group P ) , given three times at intervals of 36 hours . The patients were monitored over a seven-day period by means of the sequential organ failure assessment score . RESULTS Patients treated with dexamethasone did not require vasopressor therapy for as much time over the seven-day period as did the placebo group ( p = 0.043 ) . Seven-day mortality was 67 % in group P ( 10 out of 15 ) and 21 % in group D ( 3 out of 14 ) ( relative risk = 0.31 , 95 % confidence interval 0.11 to 0.88 ) . Dexamethasone enhanced the effects of vasopressor drugs . CONCLUSIONS Early treatment with dexamethasone reduced the seven-day mortality among septic shock patients and showed a trend towards reduction of 28-day mortality BACKGROUND Septic shock is characterized by dysregulation of the host response to infection , with circulatory , cellular , and metabolic abnormalities . We hypothesized that therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa ( activated ) , which can modulate the host response , would improve the clinical outcomes of patients with septic shock . METHODS In this multicenter , double‐blind , r and omized trial with a 2‐by‐2 factorial design , we evaluated the effect of hydrocortisone‐plus‐fludrocortisone therapy , drotrecogin alfa ( activated ) , the combination of the three drugs , or their respective placebos . The primary outcome was 90‐day all‐cause mortality . Secondary outcomes included mortality at intensive care unit ( ICU ) discharge and hospital discharge and at day 28 and day 180 and the number of days alive and free of vasopressors , mechanical ventilation , or organ failure . After drotrecogin alfa ( activated ) was withdrawn from the market , the trial continued with a two‐group parallel design . The analysis compared patients who received hydrocortisone plus fludrocortisone with those who did not ( placebo group ) . RESULTS Among the 1241 patients included in the trial , the 90‐day mortality was 43.0 % ( 264 of 614 patients ) in the hydrocortisone‐plus‐fludrocortisone group and 49.1 % ( 308 of 627 patients ) in the placebo group ( P=0.03 ) . The relative risk of death in the hydrocortisone‐plus‐fludrocortisone group was 0.88 ( 95 % confidence interval , 0.78 to 0.99 ) . Mortality was significantly lower in the hydrocortisone‐plus‐fludrocortisone group than in the placebo group at ICU discharge ( 35.4 % vs. 41.0 % , P=0.04 ) , hospital discharge ( 39.0 % vs. 45.3 % , P=0.02 ) , and day 180 ( 46.6 % vs. 52.5 % , P=0.04 ) but not at day 28 ( 33.7 % and 38.9 % , respectively ; P=0.06 ) . The number of vasopressor‐free days to day 28 was significantly higher in the hydrocortisone‐plus‐fludrocortisone group than in the placebo group ( 17 vs. 15 days , P<0.001 ) , as was the number of organ‐failure – free days ( 14 vs. 12 days , P=0.003 ) . The number of ventilator‐free days was similar in the two groups ( 11 days in the hydrocortisone‐plus‐fludrocortisone group and 10 in the placebo group , P=0.07 ) . The rate of serious adverse events did not differ significantly between the two groups , but hyperglycemia was more common in hydrocortisone‐plus‐fludrocortisone group . CONCLUSIONS In this trial involving patients with septic shock , 90‐day all‐cause mortality was lower among those who received hydrocortisone plus fludrocortisone than among those who received placebo . ( Funded by Programme Hospitalier de Recherche Clinique 2007 of the French Ministry of Social Affairs and Health ; APROCCHSS Clinical Trials.gov number , NCT00625209 . Background Authors of recent meta-analyses have reported that prolonged glucocorticoid treatment is associated with significant improvements in patients with severe pneumonia or acute respiratory distress syndrome ( ARDS ) of multifactorial etiology . A prospect i ve r and omized trial limited to patients with sepsis-associated ARDS is lacking . The objective of our study was to evaluate the efficacy of hydrocortisone treatment in sepsis-associated ARDS . Methods In this double-blind , single-center ( Siriraj Hospital , Bangkok ) , r and omized , placebo-controlled trial , we recruited adult patients with severe sepsis within 12 h of their meeting ARDS criteria . Patients were r and omly assigned ( 1:1 ratio ) to receive either hydrocortisone 50 mg every 6 h or placebo . The primary endpoint was 28-day all-cause mortality ; secondary endpoints included survival without organ support on day 28 . Results Over the course of 4 years , 197 patients were r and omized to either hydrocortisone ( n = 98 ) or placebo ( n = 99 ) and were included in this intention-to-treat analysis . The treatment group had significant improvement in the ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen and lung injury score ( p = 0.01 ) , and similar timing to removal of vital organ support ( HR 0.74 , 95 % CI 0.51–1.07 ; p = 0.107 ) . After adjustment for significant covariates , day 28 survival was similar for the whole group ( HR 0.80 , 95 % CI 0.46–1.41 ; p = 0.44 ) and for the larger subgroup ( n = 126 ) with Acute Physiology and Chronic Health Evaluation II score < 25 ( HR 0.57 , 95 % CI 0.24–1.36 ; p = 0.20 ) . With the exception of hyperglycemia ( 80.6 % vs. 67.7 % ; p = 0.04 ) , the rate of adverse events was similar . Hyperglycemia had no impact on outcome . Conclusions In sepsis-associated ARDS , hydrocortisone treatment was associated with a significant improvement in pulmonary physiology , but without a significant survival benefit . Trial registration Clinical Trials.gov identifier NCT01284452 . Registered on 18 January 2011 Background Recent studies have reported a high prevalence of relative adrenal insufficiency in patients with liver cirrhosis . However , the effect of corticosteroid replacement on mortality in this high-risk group remains unclear . We examined the effect of low-dose hydrocortisone in patients with cirrhosis who presented with septic shock . Methods We enrolled patients with cirrhosis and septic shock aged 18 years or older in a r and omized double-blind placebo-controlled trial . Relative adrenal insufficiency was defined as a serum cortisol increase of less than 250 nmol/L or 9 μg/dL from baseline after stimulation with 250 μg of intravenous corticotropin . Patients were assigned to receive 50 mg of intravenous hydrocortisone or placebo every six hours until hemodynamic stability was achieved , followed by steroid tapering over eight days . The primary outcome was 28-day all-cause mortality . Results The trial was stopped for futility at interim analysis after 75 patients were enrolled . Relative adrenal insufficiency was diagnosed in 76 % of patients . Compared with the placebo group ( n = 36 ) , patients in the hydrocortisone group ( n = 39 ) had a significant reduction in vasopressor doses and higher rates of shock reversal ( relative risk [ RR ] 1.58 , 95 % confidence interval [ CI ] 0.98–2.55 , p = 0.05 ) . Hydrocortisone use was not associated with a reduction in 28-day mortality ( RR 1.17 , 95 % CI 0.92–1.49 , p = 0.19 ) but was associated with an increase in shock relapse ( RR 2.58 , 95 % CI 1.04–6.45 , p = 0.03 ) and gastrointestinal bleeding ( RR 3.00 , 95 % CI 1.08–8.36 , p = 0.02 ) . Interpretation Relative adrenal insufficiency was very common in patients with cirrhosis presenting with septic shock . Despite initial favourable effects on hemodynamic parameters , hydrocortisone therapy did not reduce mortality and was associated with an increase in adverse effects . ( Current Controlled Trials registry no. IS RCT N99675218 . BACKGROUND In sub-Saharan Africa , bacterial meningitis is common and is associated with a high mortality . Adjuvant therapy with corticosteroids reduces mortality among adults in the developed world , but it has not been adequately tested in developing countries or in the context of advanced human immunodeficiency virus ( HIV ) infection . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of dexamethasone ( 16 mg twice daily for 4 days ) and an open-label trial of intramuscular versus intravenous ceftriaxone ( 2 g twice daily for 10 days ) in adults with an admission diagnosis of bacterial meningitis in Blantyre , Malawi . The primary outcome was death at 40 days after r and omization . RESULTS A total of 465 patients , 90 % of whom were HIV-positive , were r and omly assigned to receive dexamethasone ( 233 patients ) or placebo ( 232 patients ) plus intramuscular ceftriaxone ( 230 patients ) or intravenous ceftriaxone ( 235 patients ) . There was no significant difference in mortality at 40 days in the corticosteroid group ( 129 of 231 patients ) as compared with the placebo group ( 120 of 228 patients ) by intention-to-treat analysis ( odds ratio , 1.14 ; 95 % confidence interval [ CI ] , 0.79 to 1.64 ) or when the analysis was restricted to patients with proven pneumococcal meningitis ( 68 of 129 patients receiving corticosteroids vs. 72 of 143 patients receiving placebo ) ( odds ratio , 1.10 ; 95 % CI , 0.68 to 1.77 ) . There were no significant differences between groups in the outcomes of disability and death combined , hearing impairment , and adverse events . There was no difference in mortality with intravenous ceftriaxone ( 121 of 230 patients ) as compared with intramuscular ceftriaxone ( 128 of 229 patients ) ( odds ratio , 0.88 ; 95 % CI , 0.61 to 1.27 ) . CONCLUSIONS Adjuvant therapy with dexamethasone for bacterial meningitis in adults from an area with a high prevalence of HIV did not reduce mortality or morbidity . In this setting , intramuscular administration was not inferior to intravenous administration of ceftriaxone for bacterial meningitis . ( Current Controlled Trials number , IS RCT N31371499 [ controlled-trials.com ] . ) Introduction The aim of the study was to assess the prognostic importance of basal cortisol concentrations and cortisol response to corticotropin , and to determine the effects of physiological dose steroid therapy on mortality in patients with sepsis . Methods Basal cortisol level and corticotropin stimulation test were performed within 24 hours in all patients . One group ( 20 patients ) received st and ard therapy for sepsis and physiological-dose steroid therapy for 10 days ; the other group ( 20 patients ) received only st and ard therapy for sepsis . Basal cortisol level was measured on the 14th day in patients who recovered . The outcome of sepsis was compared . Results Only Sequential Organ Failure Assessment ( SOFA ) score was found related to mortality , independent from other factors in multivariate analysis . No significant difference was found between the changes in the percentage of SOFA scores of the steroid therapy group and the st and ard therapy group in survivors , nor between the groups in basal and peak cortisol levels , cortisol response to corticotropin test and mortality . The mortality rates among patients with occult adrenal insufficiencies were 40 % in the steroid therapy group and 55.6 % in the st and ard therapy group . Discussion There was a trend towards a decrease in the mortality rates of the patients with sepsis who received physiological-dose steroid therapy . In the advancing process from sepsis to septic shock , adrenal insufficiency was not frequent as supposed . There was a trend ( that did not reach significance ) towards a decrease in the mortality rates of the patients with sepsis who received physiological-dose steroid therapy We conducted a multicenter r and omized , double-blind , placebo-controlled trial of early short-term , high-dose methylprednisolone sodium succinate in 223 patients with clinical signs of systemic sepsis and a normal sensorium ( 112 received glucocorticoid and 111 placebo ) . Patients also received antibiotics and intravenous fluids . Glucocorticoid or placebo was administered intravenously by a bolus ( 30 mg per kilogram of body weight over 15 minutes ) followed by infusion of 5 mg per kilogram per hour for nine hours . The average time between the diagnosis of sepsis and infusion was 2.8 hours . The principal end point was 14-day mortality , which was similar in the placebo ( 22 percent ) and glucocorticoid ( 21 percent ) groups ( P = 0.97 ) . Mortality was also not significantly different between those receiving placebo and those receiving glucocorticoid in subgroups with evidence of sepsis ( 21 vs. 19 percent ) , gram-negative bacteremia ( 27 vs. 7 percent ) , gram-positive bacteremia ( 18 vs. 26 percent ) , or all gram-negative infections ( 25 vs. 17 percent ) . Resolution of secondary infection within 14 days was significantly higher in patients receiving placebo ( 12 of 23 ) than in those receiving glucocorticoid ( 3 of 16 ) ( P = 0.03 ) , but mortality rates were similar in both treatment groups for those with unresolved infection ( 36 vs. 31 percent ) . We conclude that early high-dose glucocorticoid therapy does not reduce mortality significantly in patients with systemic sepsis who have a normal sensorium , and therefore should not be used as adjunctive therapy Within the last few years , increasing evidence of relative adrenal insufficiency in septic shock evoked a re assessment of hydrocortisone therapy . To evaluate the effects of hydrocortisone on the balance between proinflammatory and antiinflammation , 40 patients with septic shock were r and omized in a double-blind crossover study to receive either the first 100 mg of hydrocortisone as a loading dose and 10 mg per hour until Day 3 ( n = 20 ) or placebo ( n = 20 ) , followed by the opposite medication until Day 6 . Hydrocortisone infusion induced an increase of mean arterial pressure , systemic vascular resistance , and a decline of heart rate , cardiac index , and norepinephrine requirement . A reduction of plasma nitrite/nitrate indicated inhibition of nitric oxide formation and correlated with a reduction of vasopressor support . The inflammatory response ( interleukin-6 and interleukin-8 ) , endothelial ( soluble E-selectin ) and neutrophil activation ( expression of CD11b , CD64 ) , and antiinflammatory response ( soluble tumor necrosis factor receptors I and II and interleukin-10 ) were attenuated . In peripheral blood monocytes , human leukocyte antigen-DR expression was only slightly depressed , whereas in vitro phagocytosis and the monocyte-activating cytokine interleukin-12 increased . Hydrocortisone withdrawal induced hemodynamic and immunologic rebound effects . In conclusion , hydrocortisone therapy restored hemodynamic stability and differentially modulated the immunologic response to stress in a way of antiinflammation rather than immunosuppression We hypothesize that hydrocortisone infusion in severe community-acquired pneumonia attenuates systemic inflammation and leads to earlier resolution of pneumonia and a reduction in sepsis-related complications . In a multicenter trial , patients admitted to the Intensive Care Unit ( ICU ) with severe community-acquired pneumonia received protocol -guided antibiotic treatment and were r and omly assigned to hydrocortisone infusion or placebo . Hydrocortisone was given as an intravenous 200-mg bolus followed by infusion at a rate of 10 mg/hour for 7 days . Primary end-points of the study were improvement in Pa(O(2)):FI(O(2 ) ) ( Pa(O(2)):FI(O(2 ) ) > 300 or > /= 100 increase from study entry ) and multiple organ dysfunction syndrome ( MODS ) score by Study Day 8 and reduction in delayed septic shock . Forty-six patients entered the study . At study entry , the hydrocortisone group had lower Pa(O(2)):FI(O(2 ) ) , and higher chest radiograph score and C-reactive protein level . By Study Day 8 , treated patients had , compared with control subjects , a significant improvement in Pa(O(2)):FI(O(2 ) ) ( p = 0.002 ) and chest radiograph score ( p < 0.0001 ) , and a significant reduction in C-reactive protein levels ( p = 0.01 ) , MODS score ( p = 0.003 ) , and delayed septic shock ( p = 0.001 ) . Hydrocortisone treatment was associated with a significant reduction in length of hospital stay ( p = 0.03 ) and mortality ( p = 0.009 ) RATIONALE Some studies have shown a beneficial effect of corticosteroids in patients with community-acquired pneumonia ( CAP ) , possibly by diminishing local and systemic antiinflammatory host response . OBJECTIVES To assess the efficacy of adjunctive prednisolone treatment in patients hospitalized with CAP . METHODS Hospitalized patients , clinical ly and radiologically diagnosed with CAP using st and ard clinical and radiological criteria , were r and omized to receive 40 mg prednisolone for 7 days or placebo , along with antibiotics . Primary outcome was clinical cure at Day 7 . Secondary outcomes were clinical cure at Day 30 , length of stay , time to clinical stability , defervescence , and C-reactive protein . Disease severity was scored using CURB-65 ( a severity index for community-acquired pneumonia evaluating Confusion , blood Urea nitrogen , Respiratory rate , Blood pressure , and age 65 or older ) and Pneumonia Severity Index . MEASUREMENTS AND MAIN RESULTS We enrolled 213 patients . Fifty-four ( 25.4 % ) patients had a CURB-65 score greater than 2 , and 93 ( 43.7 % ) patients were in Pneumonia Severity Index class IV-V. Clinical cure at Days 7 and 30 was 84/104 ( 80.8 % ) and 69/104 ( 66.3 % ) in the prednisolone group and 93/109 ( 85.3 % ) and 84/109 ( 77.1 % ) in the placebo group ( P = 0.38 and P = 0.08 ) . Patients on prednisolone had faster defervescence and faster decline in serum C-reactive protein levels compared with placebo . Sub analysis of patients with severe pneumonia did not show differences in clinical outcome . Late failure ( > 72 h after admittance ) was more common in the prednisolone group ( 20 patients , 19.2 % ) than in the placebo group ( 10 patients , 6.4 % ; P = 0.04 ) . Adverse events were few and not different between the two groups . CONCLUSIONS Prednisolone ( at 40 mg ) once daily for a week does not improve outcome in hospitalized patients with CAP . A benefit in more severely ill patients can not be excluded . Because of its association with increased late failure and lack of efficacy prednisolone should not be recommended as routine adjunctive treatment in CAP BACKGROUND Whether addition of corticosteroids to antibiotic treatment benefits patients with community-acquired pneumonia who are not in intensive care units is unclear . We aim ed to assess effect of addition of dexamethasone on length of stay in this group , which might result in earlier resolution of pneumonia through dampening of systemic inflammation . METHODS In our double-blind , placebo-controlled trial , we r and omly assigned adults aged 18 years or older with confirmed community-acquired pneumonia who presented to emergency departments of two teaching hospitals in the Netherl and s to receive intravenous dexamethasone ( 5 mg once a day ) or placebo for 4 days from admission . Patients were ineligible if they were immunocompromised , needed immediate transfer to an intensive-care unit , or were already receiving corticosteroids or immunosuppressive drugs . We r and omly allocated patients on a one-to-one basis to treatment groups with a computerised r and omisation allocation sequence in blocks of 20 . The primary outcome was length of hospital stay in all enrolled patients . This study is registered with Clinical Trials.gov , number NCT00471640 . FINDINGS Between November , 2007 , and September , 2010 , we enrolled 304 patients and r and omly allocated 153 to the placebo group and 151 to the dexamethasone group . 143 ( 47 % ) of 304 enrolled patients had pneumonia of pneumonia severity index class 4 - 5 ( 79 [ 52 % ] patients in the dexamethasone group and 64 [ 42 % ] controls ) . Median length of stay was 6·5 days ( IQR 5·0 - 9·0 ) in the dexamethasone group compared with 7·5 days ( 5·3 - 11·5 ) in the placebo group ( 95 % CI of difference in medians 0 - 2 days ; p=0·0480 ) . In-hospital mortality and severe adverse events were infrequent and rates did not differ between groups , although 67 ( 44 % ) of 151 patients in the dexamethasone group had hyperglycaemia compared with 35 ( 23 % ) of 153 controls ( p<0·0001 ) . INTERPRETATION Dexamethasone can reduce length of hospital stay when added to antibiotic treatment in non-immunocompromised patients with community-acquired pneumonia . FUNDING None Objectives : Vasopressin and corticosteroids are both commonly used adjunctive therapies in septic shock . Retrospective analyses have suggested that there may be an interaction between these drugs , with higher circulating vasopressin levels and improved outcomes in patients treated with both vasopressin and corticosteroids . We aim ed to test for an interaction between vasopressin and corticosteroids in septic shock . Design : Prospect i ve open-label r and omized controlled pilot trial . Setting : Four adult ICUs in London teaching hospitals . Patients : Sixty-one adult patients who had septic shock . Interventions : Initial vasopressin IV infusion titrated up to 0.06 U/min and then IV hydrocortisone ( 50 mg 6 hourly ) or placebo . Plasma vasopressin levels were measured at 6–12 and 24–36 hours after hydrocortisone/placebo administration . Measurements and Main Results : Thirty-one patients were allocated to vasopressin + hydrocortisone and 30 patients to vasopressin + placebo . The hydrocortisone group required a shorter duration of vasopressin therapy ( 3.1 d ; 95 % CI , 1.1–5.1 ; shorter in hydrocortisone group ) and required a lower total dose of vasopressin ( ratio , 0.47 ; 95 % CI , 0.32–0.71 ) compared with the placebo group . Plasma vasopressin levels were not higher in the hydrocortisone group compared with the placebo group ( 64 pmol/L difference at 6- to 12-hour time point ; 95 % CI , –32 to 160 pmol/L ) . Early vasopressin use was well tolerated with only one serious adverse event possibly related to study drug administration reported . There were no differences in mortality rates ( 23 % 28-day mortality in both groups ) or organ failure assessment s between the two treatment groups . Conclusions : Hydrocortisone spared vasopressin requirements , reduced duration , and reduced dose , when used together in the treatment of septic shock , but it did not alter plasma vasopressin levels . Further trials are needed to assess the clinical effectiveness of vasopressin as the initial vasopressor therapy with or without corticosteroids Background Physiologic dose hydrocortisone is part of the suggested adjuvant therapies for patients with septic shock . However , the association between the corticosteroid therapy and mortality in patients with septic shock is still not clear . Some authors considered that the mortality is related to the time frame between development of septic shock and start of low dose hydrocortisone . Thus we design ed a placebo‐controlled , r and omized clinical trial to assess the importance of early initiation of low dose hydrocortisone for the final outcome . Methods A total of 118 patients with septic shock were recruited in the study . All eligible patients were r and omized to receive hydrocortisone ( n = 58 ) or normal saline ( n = 60 ) . The study medication ( hydrocortisone and normal saline ) was initiated simultaneously with vasopressors . The primary end‐point was 28‐day mortality . The secondary end‐points were the reversal of shock , in‐hospital mortality and the duration of ICU and hospital stay . Results The proportion of patients with reversal of shock was similar in the two groups ( P = 0.602 ) ; There were no significant differences in 28‐day or hospital all‐cause mortality ; length of stay in the ICU or hospital between patients treated with hydrocortisone or normal saline . Conclusion The early initiation of low‐dose of hydrocortisone did not decrease the risk of mortality , and the length of stay in the ICU or hospital in adults with septic shock . Trial registration : www . clinical trials.gov NCT02580240 Objectives : To investigate the effect of low-dose hydrocortisone on time to shock reversal , the cytokine profile , and its relation to adrenal function in patients with early septic shock . Design : Prospect i ve , r and omized , double-blind , single-center study . Setting : Medical intensive care unit of a university hospital . Patients : Forty-one consecutive patients with early hyperdynamic septic shock . Interventions : After inclusion and a short adrenocorticotropic hormone test , all patients were r and omized to receive either low-dose hydrocortisone ( 50-mg bolus followed by a continuous infusion of 0.18 mg/kg body of weight/hr ) or matching placebo . After shock reversal , the dose was reduced to 0.06 mg/kg/hr and afterward slowly tapered . Severity of illness was estimated using Acute Physiology and Chronic Health Evaluation II score and Sequential Organ Failure Assessment score . Measurements and Main Results : Time to cessation of vasopressor support ( primary end point ) was significantly shorter in hydrocortisone-treated patients compared with placebo ( 53 hrs vs. 120 hrs , p < .02 ) . This effect was more profound in patients with impaired adrenal reserve . Irrespective of endogenous steroid production , cytokine production was reduced in the treatment group with lower plasma levels of interleukin-6 and a diminished ex vivo lipopolysaccharide-stimulated interleukin-1 and interleukin-6 production . Interleukin-10 levels were unaltered . Adverse events were not more frequent in the treatment group . Conclusions : Treatment with low-dose hydrocortisone accelerates shock reversal in early hyperdynamic septic shock . This was accompanied by reduced production of proinflammatory cytokines , suggesting both hemodynamic and immunomodulatory effects of steroid treatment . Hemodynamic improvement seemed to be related to endogenous cortisol levels , whereas immune effects appeared to be independent of adrenal reserve OBJECTIVE To determine the effects of low-dose prolonged methylprednisolone infusion on lung function in patients with early severe ARDS . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING ICUs of five hospitals in Memphis . PARTICIPANTS Ninety-one patients with severe early ARDS ( < /= 72 h ) , 66 % with sepsis . INTERVENTIONS Patients were r and omized ( 2:1 fashion ) to methylprednisolone infusion ( 1 mg/kg/d ) vs placebo . The duration of treatment was up to 28 days . Infection surveillance and avoidance of paralysis were integral components of the protocol . MAIN OUTCOME MEASURE The predefined primary end point was a 1-point reduction in lung injury score ( LIS ) or successful extubation by day 7 . RESULTS In intention-to-treat analysis , the response of the two groups ( 63 treated and 28 control ) clearly diverged by day 7 , with twice the proportion of treated patients achieving a 1-point reduction in LIS ( 69.8 % vs 35.7 % ; p = 0.002 ) and breathing without assistance ( 53.9 % vs 25.0 % ; p = 0.01 ) . Treated patients had significant reduction in C-reactive protein levels , and by day 7 had lower LIS and multiple organ dysfunction syndrome scores . Treatment was associated with a reduction in the duration of mechanical ventilation ( p = 0.002 ) , ICU stay ( p = 0.007 ) , and ICU mortality ( 20.6 % vs 42.9 % ; p = 0.03 ) . Treated patients had a lower rate of infections ( p = 0.0002 ) , and infection surveillance identified 56 % of nosocomial infections in patients without fever . CONCLUSIONS Methylprednisolone-induced down-regulation of systemic inflammation was associated with significant improvement in pulmonary and extrapulmonary organ dysfunction and reduction in duration of mechanical ventilation and ICU length of stay We conducted a prospect i ve , r and omized , double-blind study to determine whether high-dose methylprednisolone could prevent parenchymal lung injury , including the adult respiratory distress syndrome ( ARDS ) , or improve mortality when administered early in septic shock . All patients already hospitalized in or newly admitted to the medical and surgical intensive care units at San Francisco General Hospital between September 1 , 1983 and August 29 , 1986 were eligible for admission to the study if they had either ( 1 ) an increase in temperature of 1.5 degrees C and a decrease in systolic blood pressure of 20 mm Hg or more from baseline values ( in already hospitalized patients ) , or ( 2 ) a temperature greater than 38.5 degrees C or less than 35.5 degrees C and a systolic blood pressure of less than 90 mm Hg ( in newly admitted patients ) . Patients meeting these criteria were excluded if they ( 1 ) had severe immunodeficiency , ( 2 ) were less than 18 or greater than 76 yr of age , ( 3 ) had multilobar roentgenographic infiltrates , or ( 4 ) were already receiving corticosteroids . Eighty-seven patients enrolled in the study received either methylprednisolone , 30 mg/kg per dose , or mannitol placebo for a total of 4 doses every 6 h , following the presumptive diagnosis of septic shock . Of these patients , 75 ultimately were determined on the basis of culture results to have actually had septic shock at the time of entry . Thirteen of the patients who received methylprednisolone developed ARDS , compared to 14 patients who received placebo . Lesser degrees of parenchymal lung injury did not differ between the 2 groups . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To observe the effect of low-dose hydrocortisone on the requirement of norepinephrine and lactate clearance in patients with refractory septic shock , and to investigate the effect of stress dose corticosteroids in reversing septic shock and improving tissue oxygen supply . METHODS Seventy-seven septic shock patients with hypotension refractory to fluids and administration of norepinephrine were r and omly divided into control and treatment groups . In treatment group intravenous injection of low-dose hydrocortisone was given on top of the treatment given in control group for 14 days . The mean arterial pressure ( MAP ) , lactate clearance and the data of norepinephrine use were compared between two groups during the course of treatment . RESULTS The number of patients requiring norepinephrine was significantly lower and the MAP was significantly higher in 24 hours , 7 days , 14 days than those at the beginning of treatment in both groups ( all P<0.01 ) . Compare to the control group , the course of using norepinephrine was shorter and the number of using norepinephrine was smaller in 7 days in treatment group ( both P<0.05 ) ; the MAP and lactate clearance were higher in 24 hours and 7 days in treatment group ( P<0.05 or P<0.01 ) . But there were no differences in mortality and the length of stay in intensive care unit ( ICU ) . CONCLUSION For the patients with septic shock with refractory hypotension , low-dose hydrocortisone can decrease the time course and dosage of vasopressors , improve tissue oxygen supply , thus can reverse septic shock more rapidly OBJECTIVE To investigate the effect of stress dose glucocorticoid on patients with acute respiratory distress syndrome ( ARDS ) combined with critical illness-related corticosteroid insufficiency ( CIRCI ) . METHODS All early ARDS patients combined with CIRCI were screened by an adrenal corticotrophic hormone ( ACTH ) test and r and omly divided into treatment group ( hydrocortisone 100 mg intravenous , 3 times/day , consecutively for 7 days , n = 12 ) and control group ( equivalent normal saline , n = 14 ) . General clinical data , changes of arterial blood gas , hemodynamics and respiratory mechanics were observed and recorded at admission and at 7 days after treatment . Ventilator-free and shock-free days , ICU stay within 28 days after admission were recorded and 28-day mortality was used as judge prognosis index . RESULTS CIRCI rate in 45 early ARDS patients was 57.8 % ( 26 patients ) , and the shock rate was markedly higher in ARDS patients with CIRCI than patients without CIRCI ( 46.2 % vs 5/19 ) . There were no significant differences in baseline parameters , oxygenation and illness severity between the treatment and control groups , except for markedly lower lactic level in the treatment group [ 2.7(1.2 , 3.9 ) mmol/L vs 4.6(2.5 , 6.3 ) mmol/L , P < 0.05 ] . After 7 days of treatment , PaO2/FiO2 markedly increased , while heart rate obviously decreased in the both groups . Compared with the control group , survival time of patients was significantly longer and shock rate of the patients was markedly lower in treatment group within 28 days ( 5/12 vs 10/14 , P < 0.05 ) . The 28-day mortality , which were adjusted by baseline arterial lactic , was lower in the treatment group ( 2.6/12 ) than in the control group ( 5.8/14 ) while with no significant difference ( P > 0.05 ) . There was no significant difference in complication incidence between the two groups . CONCLUSION Stress dose glucocorticoid could reduce shock incidence and prolong survival time , and has a tendency of lower 28-day mortality in early ARDS patients combined with CIRCI OBJECTIVES Preliminary studies have suggested that low doses of corticosteroids might rapidly improve hemodynamics in late septic shock treated with catecholamines . We examined the effect of hydrocortisone on shock reversal , hemodynamics , and survival in this particular setting . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled study . SETTING Two intensive care units of a University hospital . PATIENTS Forty-one patients with septic shock requiring catecholamine for > 48 hrs . INTERVENTIONS Patients were r and omly assigned either hydrocortisone ( 100 mg i.v . three times daily for 5 days ) or matching placebo . MEASUREMENTS AND MAIN RESULTS Reversal of shock was defined by a stable systolic arterial pressure ( > 90 mm Hg ) for > or = 24 hrs without catecholamine or fluid infusion . Of the 22 hydrocortisone-treated patients and 19 placebo-treated patients , 15 ( 68 % ) and 4 ( 21 % ) achieved 7-day shock reversal , respectively , a difference of 47 % ( 95 % confidence interval 17 % to 77 % ; p = .007 ) . Serial invasive hemodynamic measurements for 5 days did not show significant differences between both groups . At 28-day follow-up , reversal of shock was higher in the hydrocortisone group ( p = .005 ) . Crude 28-day mortality was 7 ( 32 % ) of 22 treated patients and 12 ( 63 % ) of 19 placebo patients , a difference of 31 % ( 95 % confidence interval 1 % to 61 % ; p = .091 ) . Shock reversal within 7 days after the onset of corticosteroid therapy was a very strong predictor of survival . There were no significant differences in outcome in responders and nonresponders to a short corticotropin test . The respective rates of gastrointestinal bleeding and secondary infections did not differ between both groups . CONCLUSIONS Administration of modest doses of hydrocortisone in the setting of pressor-dependent septic shock for a mean of > 96 hrs result ed in a significant improvement in hemodynamics and a beneficial effect on survival . These beneficial effects do not appear related to adrenocortical insufficiency BACKGROUND Hydrocortisone is widely used in patients with septic shock even though a survival benefit has been reported only in patients who remained hypotensive after fluid and vasopressor resuscitation and whose plasma cortisol levels did not rise appropriately after the administration of corticotropin . METHODS In this multicenter , r and omized , double-blind , placebo-controlled trial , we assigned 251 patients to receive 50 mg of intravenous hydrocortisone and 248 patients to receive placebo every 6 hours for 5 days ; the dose was then tapered during a 6-day period . At 28 days , the primary outcome was death among patients who did not have a response to a corticotropin test . RESULTS Of the 499 patients in the study , 233 ( 46.7 % ) did not have a response to corticotropin ( 125 in the hydrocortisone group and 108 in the placebo group ) . At 28 days , there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin ( 39.2 % in the hydrocortisone group and 36.1 % in the placebo group , P=0.69 ) or between those who had a response to corticotropin ( 28.8 % in the hydrocortisone group and 28.7 % in the placebo group , P=1.00 ) . At 28 days , 86 of 251 patients in the hydrocortisone group ( 34.3 % ) and 78 of 248 patients in the placebo group ( 31.5 % ) had died ( P=0.51 ) . In the hydrocortisone group , shock was reversed more quickly than in the placebo group . However , there were more episodes of superinfection , including new sepsis and septic shock . CONCLUSIONS Hydrocortisone did not improve survival or reversal of shock in patients with septic shock , either overall or in patients who did not have a response to corticotropin , although hydrocortisone hastened reversal of shock in patients in whom shock was reversed . ( Clinical Trials.gov number , NCT00147004 . STEROIDS might be of benefit to the patient with a serious infection.1 In 1961 a Cooperative double-blind study of the effects of administering a dose of 300 mg of hydrocortisone to patients with s Objective : The aim of this study was to investigate the effect of low-dose hydrocortisone on glomerular permeability measured by the microalbuminuria to creatinine ratio ( MACR ) and on other markers of sepsis in severe septic patients . Design : R and omized prospect i ve study . Setting : University intensive care unit . Patients : The study involved 40 patients with severe sepsis r and omized into the hydrocortisone group ( n = 20 ) and the st and ard therapy group ( n = 20 ) . Interventions : The hydrocortisone group received st and ard therapy plus a continuous infusion of hydrocortisone for 6 days , whereas the st and ard therapy group received only st and ard therapy . Measurements and Main Results : MACR , serum C-reactive protein , and procalcitonin concentrations were recorded every day from the day before the steroid therapy ( T0 ) until the 6 days after ( T1 , T2 , T3 , T4 , T5 , and T6 ) . Concentrations in the hydrocortisone group and the st and ard therapy group were compared using Mann-Whitney test at each time . We also compared with Wilcoxon signed rank test the values determined in each group at T0 with those at each subsequent time . Median MACR decreased from T0 to T6 in both patient groups ; however , values were significantly lower in the hydrocortisone group from T3 through to T6 . Median serum C-reactive protein also decreased from T0 in both patient groups , with significantly lower values in the hydrocortisone group from T3 through to T6 . There were no significant differences in procalcitonin between groups compared with baseline values or at any individual time point . Conclusions : Low-dose hydrocortisone seems to reduce MACR and serum C-reactive protein but not procalcitonin in patients with severe sepsis . Further studies are needed to confirm these results and to underst and the underlying molecular mechanisms A prospect i ve ( Part I ) and a retrospective ( Part II ) study were used to determine the safety and efficacy of corticosteroids in the treatment of septic shock . In Part 1 , 172 consecutive patients in septic shock admitted over an 8-year period were treated with either steroid or saline : 43 received dexamethasone ( DMP ) , 43 received methylprednisolone ( MPS ) , and 86 received saline . The study was double-blind and r and omized , and the three groups were compared for age , severity of shock , presence of underlying disease , and year of study . In the 86 saline-treated patients , the mortality rate was 38.4 % ( 33/86 ) ; in the steroid-treated patients , it was 10.4 % ( 9/86 ) . With MPS the mortality rate was 11.6 % ( 5/43 ) , and with DMP it was 9.3 % ( 4/43 ) . Thus , overall mortality was significantly less in the steroid-treated group than in the control group . Further , there was no significant difference in mortality rate between the DMP- and the MPS-treated patients . In Part II , 328 patients were studied retrospectively . One-hundred sixty were treated without steroid , and 168 were treated with either DMP or MPS . Again , the two groups of patients were compared for severity of shock , underlying disease , age , and year of study . Mortality among patients treated without steroid was 42.5 % ( 68/160 ) and among patients treated with steroid was 14 % ( 24/168 ) ; there was no significant difference in mortality rate between DMP- and MPS-treated patients . In Parts I and II combined , complications occurred in 6 % of steroid-treated patients with no significant difference between DMP- and MPS-treated groups Rational : Septic shock may be associated with a loss in cardiovascular variability and adrenal dysfunction . Objectives : To investigate the relationship between cardiovascular autonomic modulation and adrenal function during sepsis . Measurement and Main Results : Seventy-five volunteers with septic shock and six healthy volunteers were prospect ively included in the study . Cardiovascular variability was assessed by spectral analysis of heart rate and diastolic blood pressure signals , which included computation of normalized low ( LFnu ) and high frequency ( HFnu ) components . Cardiovascular variability was investigated in patients and healthy volunteers immediately before and 1 hr after a single bolus of 50 mg of hydrocortisone ( study phase I ) ; in patients according to adrenal function ( study phase II ) ; and in patients with septic shock and adrenal insufficiency , before and 72 hrs after a treatment with 50 mg every 6 hrs of hydrocortisone and 50 & mgr;g daily of fludrocortisone or their placebos ( study phase III ) . As compared to healthy volunteers , patients had decreased LFnu-HR ( .16 ± .05 vs. .23 ± .07 p = .01 ) and LFnu-DBP ( .18 ± .11 vs. .28 ± .02 p = .01 ) and , after hydrocortisone , they had a greater increase in LFnu-DBP ( p = .01 ) . As compared to patients with normal adrenal function , those with adrenal failure had decreased LFnu-HR ( .1 ± .01 vs. .2 ± .15 p = .01 ) and LFnu-DBP ( .008 ± .01 vs. .14 ± .22 p = .0003 ) . In patients with adrenal failure , as compared to placebos , hydrocortisone plus fludrocortisone increased significantly LFnu-DBP ( p = .02 ) and low frequency/high volume ratio ( p = .009 ) . Conclusion : In septic shock , the loss in cardiovascular variability is more marked in patients with adrenal insufficiency and is partly restored by exogenous administration of corticosteroids OBJECTIVE To investigate the effects of stress doses of hydrocortisone on the duration of vasopressor therapy in human septic shock . DESIGN Prospect i ve , r and omized , double-blind , single-center study . SETTING Twenty-bed multidisciplinary intensive care unit in a 1400-bed university hospital . PATIENTS Forty consecutive patients who met the ACCP/SCCM criteria for septic shock . An additional criterion for inclusion in the study was vasopressor support and high-output circulatory failure with a cardiac index of > 4 L/min/m2 after fluid resuscitation ( pulmonary capillary wedge pressure : 12 - 15 mm Hg ) and without the use of positive inotropes such as dobutamine or dopexamine . The primary study end point was the time to cessation of vasopressor support ( norepinephrine or epinephrine in any dose , dopamine > or = 6 microg/kg/min ) . Secondary study end points were the evolution of hemodynamics and the multiple organ dysfunction syndrome ( MODS ) . The severity of illness at recruitment was grade d using the Acute Physiology and Chronic Health Evaluation II and the Simplified Acute Physiology Score II scoring systems . MODS was described by the Sepsis-related Organ Failure Assessment score . INTERVENTIONS All eligible patients were prospect ively r and omized to receive either stress doses of hydrocortisone or placebo . Hydrocortisone was started with a loading dose of 100 mg given within 30 mins and followed by a continuous infusion of 0.18 mg/ kg/hr . When septic shock had been reversed , the dose of hydrocortisone was reduced to 0.08 mg/kg/hr . This dose was kept constant for 6 days . As soon as the underlying infection had been treated successfully or sodium serum concentrations had increased to > 155 mmol/L , the hydrocortisone infusion was tapered in steps of 24 mg/day . Physiologic saline solution was the placebo . MEASUREMENTS AND MAIN RESULTS Hemodynamic and oxygen-derived variables were measured at previously defined time points over a study period of 5 days . Relevant clinical and laboratory measurements were registered for a study period of 14 days to assess the evolution of organ dysfunction . Baseline data at recruitment did not differ between the two groups . Shock reversal was achieved in 18 of the 20 patients treated with hydrocortisone vs. 16 of the 20 patients treated with placebo . Hydrocortisone significantly reduced the time to cessation of vasopressor support . The median time of vasopressor support was 2 days ( 1st and 3rd Quartiles , 1 and 6 days ) in the hydrocortisone-treated group and 7 days ( 1st and 3rd Quartiles , 3 and 19 days ) in the placebo group ( p = .005 Breslow test ) . There was a trend to earlier resolution of the organ dysfunction syndrome in the hydrocortisone group . CONCLUSIONS Infusion of stress doses of hydrocortisone reduced the time to cessation of vasopressor therapy in human septic shock . This was associated with a trend to earlier resolution of sepsis-induced organ dysfunctions . Overall shock reversal and mortality were not significantly different between the groups in this low-sized single-center study CONTEXT Septic shock may be associated with relative adrenal insufficiency . Thus , a replacement therapy of low doses of corticosteroids has been proposed to treat septic shock . OBJECTIVE To assess whether low doses of corticosteroids improve 28-day survival in patients with septic shock and relative adrenal insufficiency . DESIGN AND SETTING Placebo-controlled , r and omized , double-blind , parallel-group trial performed in 19 intensive care units in France from October 9 , 1995 , to February 23 , 1999 . PATIENTS Three hundred adult patients who fulfilled usual criteria for septic shock were enrolled after undergoing a short corticotropin test . INTERVENTION Patients were r and omly assigned to receive either hydrocortisone ( 50-mg intravenous bolus every 6 hours ) and fludrocortisone ( 50- micro g tablet once daily ) ( n = 151 ) or matching placebos ( n = 149 ) for 7 days . MAIN OUTCOME MEASURE Twenty-eight-day survival distribution in patients with relative adrenal insufficiency ( nonresponders to the corticotropin test ) . RESULTS One patient from the corticosteroid group was excluded from analyses because of consent withdrawal . There were 229 nonresponders to the corticotropin test ( placebo , 115 ; corticosteroids , 114 ) and 70 responders to the corticotropin test ( placebo , 34 ; corticosteroids , 36 ) . In nonresponders , there were 73 deaths ( 63 % ) in the placebo group and 60 deaths ( 53 % ) in the corticosteroid group ( hazard ratio , 0.67 ; 95 % confidence interval , 0.47 - 0.95 ; P = .02 ) . Vasopressor therapy was withdrawn within 28 days in 46 patients ( 40 % ) in the placebo group and in 65 patients ( 57 % ) in the corticosteroid group ( hazard ratio , 1.91 ; 95 % confidence interval , 1.29 - 2.84 ; P = .001 ) . There was no significant difference between groups in responders . Adverse events rates were similar in the 2 groups . CONCLUSION In our trial , a 7-day treatment with low doses of hydrocortisone and fludrocortisone significantly reduced the risk of death in patients with septic shock and relative adrenal insufficiency without increasing adverse events OBJECTIVE To investigate the effects of Sini decoction on function of hypothalamic-pituitary-adrenal axis in patients with sepsis . METHODS A prospect i ve single-blind r and omized controlled trial was conducted . 60 septic patients were divided into three groups with the method of r and om number table , 20 cases in the control group , 20 in the Chinese herb group , and 20 in corticoid group . All of them received routine treatment . Patients in Chinese herb group were given Sini decoction in addition ( decoction of monkshood 15 g , dried ginger 15 g , honey-fried licorice 10 g ) 100 mL/d orally or by nasal feeding , while patients in corticoid group were given hydrocortisone 200 mg/d intravenously instead , both for 7 days . Before the treatment , 3 days and 14 days after treatment , blood was collected to determine the levels of adrenocorticotropic hormone ( ACTH ) and cortisol , and the result of ACTH stimulating test was observed . At the same time , acute physiology and chronic health evaluation II ( APACHEII ) score was recorded , and 3-day shock recovery rate and 28-day death rate were also compared among these groups . RESULTS None of the three groups showed different result in ACTH stimulating test ( χ(2)=1.101 , P=0.605 ) . ACTH in three groups was gradually decreased . Compared with that before treatment , ACTH in Chinese herb group and corticoid groups began to decrease obviously on day 3 ( 29.90±3.31 ng/L vs. 33.10±3.31 ng/L , 28.20±2.45 ng/L vs. 33.30±3.84 ng/L , both P<0.01 ) , while in control group declined ACTH appeared later ( on day 14 ) compared with before treatment ( 29.40±5.63 ng/L vs. 33.50±4.89 ng/L , P<0.05 ) . No obvious difference in ACTH level was showed between the Chinese herb group and the cortical group ( both P>0.05 ) . Cortisol level in both Chinese herb and cortical groups showed a raise-fall biphase trend while there was no change in the control . The cortical levels on day 3 in Chinese herb and cortical groups were much higher than that before treatment ( 343.04±31.20 μg/L vs. 294.70±42.10 μg/L , 331.25±42.80 μg/L vs. 280.36±38.10 μg/L , both P<0.01 ) and that of control group ( 291.61±41.50 μg/L , both P<0.01 ) , though no significant statistical difference was observed between two groups ( both P>0.05 ) . APACHEII score on day 14 in control , Chinese herb and cortical groups was significantly lower than that before treatment ( 16.8±5.1 vs. 20.1±4.3 , 13.4±3.2 vs. 18.3±3.8,15.1±2.5 vs. 19.5±4.0 , all P<0.01 ) , and the score was much lower in Chinese herb group comparing with that of control group ( P<0.05 ) . No statistical difference was observed among control , Chinese herb and cortical groups in lowering 28-day death rate [ 35.0 % ( 7/20 ) , 25.0 % ( 5/20 ) , 20.0 % ( 4/20 ) ] and improving 3-day shock recovery rate [ 40.0 % ( 8/20 ) , 70.0 % ( 14/20 ) , 60.0 % ( 12/20 ) , all P>0.05 ] . CONCLUSIONS Sini decoction could elevate cortisol while lower ACTH at the early stage of sepsis . Sini decoction could also effectively improve symptoms and hypothalamic-pituitary-adrenal axis function in septic patients without affecting death rate The use of high-dose corticosteroids in the treatment of severe sepsis and septic shock remains controversial . Our study was design ed as a prospect i ve , r and omized , double-blind , placebo-controlled trial of high-dose methylprednisolone sodium succinate for severe sepsis and septic shock . Diagnosis was based on the clinical suspicion of infection plus the presence of fever or hypothermia ( rectal temperature greater than 38.3 degrees C [ 101 degrees F ] or less than 35.6 degrees C [ 96 degrees F ] ) , tachypnea ( greater than 20 breaths per minute ) , tachycardia ( greater than 90 beats per minute ) , and the presence of one of the following indications of organ dysfunction : a change in mental status , hypoxemia , elevated lactate levels , or oliguria . Three hundred eighty-two patients were enrolled . Treatment -- either methylprednisolone sodium succinate ( 30 mg per kilogram of body weight ) or placebo -- was given in four infusions , starting within two hours of diagnosis . No significant differences were found in the prevention of shock , the reversal of shock , or overall mortality . In the subgroup of patients with elevated serum creatinine levels ( greater than 2 mg per deciliter ) at enrollment , mortality at 14 days was significantly increased among those receiving methylprednisolone ( 46 of 78 [ 59 percent ] vs. 17 of 58 [ 29 percent ] among those receiving placebo ; P less than 0.01 ) . Among patients treated with methylprednisolone , significantly more deaths were related to secondary infection . We conclude that the use of high-dose corticosteroids provides no benefit in the treatment of severe sepsis and septic shock IMPORTANCE Norepinephrine is currently recommended as the first-line vasopressor in septic shock ; however , early vasopressin use has been proposed as an alternative . OBJECTIVE To compare the effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock . DESIGN , SETTING , AND PARTICIPANTS A factorial ( 2 × 2 ) , double-blind , r and omized clinical trial conducted in 18 general adult intensive care units in the United Kingdom between February 2013 and May 2015 , enrolling adult patients who had septic shock requiring vasopressors despite fluid resuscitation within a maximum of 6 hours after the onset of shock . INTERVENTIONS Patients were r and omly allocated to vasopressin ( titrated up to 0.06 U/min ) and hydrocortisone ( n = 101 ) , vasopressin and placebo ( n = 104 ) , norepinephrine and hydrocortisone ( n = 101 ) , or norepinephrine and placebo ( n = 103 ) . MAIN OUTCOMES AND MEASURES The primary outcome was kidney failure-free days during the 28-day period after r and omization , measured as ( 1 ) the proportion of patients who never developed kidney failure and ( 2 ) median number of days alive and free of kidney failure for patients who did not survive , who experienced kidney failure , or both . Rates of renal replacement therapy , mortality , and serious adverse events were secondary outcomes . RESULTS A total of 409 patients ( median age , 66 years ; men , 58.2 % ) were included in the study , with a median time to study drug administration of 3.5 hours after diagnosis of shock . The number of survivors who never developed kidney failure was 94 of 165 patients ( 57.0 % ) in the vasopressin group and 93 of 157 patients ( 59.2 % ) in the norepinephrine group ( difference , -2.3 % [ 95 % CI , -13.0 % to 8.5 % ] ) . The median number of kidney failure-free days for patients who did not survive , who experienced kidney failure , or both was 9 days ( interquartile range [ IQR ] , 1 to -24 ) in the vasopressin group and 13 days ( IQR , 1 to -25 ) in the norepinephrine group ( difference , -4 days [ 95 % CI , -11 to 5 ] ) . There was less use of renal replacement therapy in the vasopressin group than in the norepinephrine group ( 25.4 % for vasopressin vs 35.3 % for norepinephrine ; difference , -9.9 % [ 95 % CI , -19.3 % to -0.6 % ] ) . There was no significant difference in mortality rates between groups . In total , 22 of 205 patients ( 10.7 % ) had a serious adverse event in the vasopressin group vs 17 of 204 patients ( 8.3 % ) in the norepinephrine group ( difference , 2.5 % [ 95 % CI , -3.3 % to 8.2 % ] ) . CONCLUSIONS AND RELEVANCE Among adults with septic shock , the early use of vasopressin compared with norepinephrine did not improve the number of kidney failure-free days . Although these findings do not support the use of vasopressin to replace norepinephrine as initial treatment in this situation , the confidence interval included a potential clinical ly important benefit for vasopressin , and larger trials may be warranted to assess this further . TRIAL REGISTRATION clinical trials.gov Identifier : IS RCT N 20769191 Importance Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only . The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial . Objective To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock . Design , Setting , and Participants Double-blind , r and omized clinical trial conducted from January 13 , 2009 , to August 27 , 2013 , with a follow-up of 180 days until February 23 , 2014 . The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany , and it included 380 adult patients with severe sepsis who were not in septic shock . Interventions Patients were r and omly allocated 1:1 either to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 ( n = 190 ) or to receive placebo ( n = 190 ) . Main Outcomes and Measures The primary outcome was development of septic shock within 14 days . Secondary outcomes were time until septic shock , mortality in the intensive care unit or hospital , survival up to 180 days , and assessment of secondary infections , weaning failure , muscle weakness , and hyperglycemia ( blood glucose level > 150 mg/dL [ to convert to millimoles per liter , multiply by 0.0555 ] ) . Results The intention-to-treat population consisted of 353 patients ( 64.9 % male ; mean [ SD ] age , 65.0 [ 14.4 ] years ) . Septic shock occurred in 36 of 170 patients ( 21.2 % ) in the hydrocortisone group and 39 of 170 patients ( 22.9 % ) in the placebo group ( difference , -1.8 % ; 95 % CI , -10.7 % to 7.2 % ; P = .70 ) . No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock ; mortality in the intensive care unit or in the hospital ; or mortality at 28 days ( 15 of 171 patients [ 8.8 % ] vs 14 of 170 patients [ 8.2 % ] , respectively ; difference , 0.5 % ; 95 % CI , -5.6 % to 6.7 % ; P = .86 ) , 90 days ( 34 of 171 patients [ 19.9 % ] vs 28 of 168 patients [ 16.7 % ] ; difference , 3.2 % ; 95 % CI , -5.1 % to 11.4 % ; P = .44 ) , and 180 days ( 45 of 168 patients [ 26.8 % ] vs 37 of 167 patients [ 22.2 % ] , respectively ; difference , 4.6 % ; 95 % CI , -4.6 % to 13.7 % ; P = .32 ) . In the hydrocortisone vs placebo groups , 21.5 % vs 16.9 % had secondary infections , 8.6 % vs 8.5 % had weaning failure , 30.7 % vs 23.8 % had muscle weakness , and 90.9 % vs 81.5 % had hyperglycemia . Conclusions and Relevance Among adults with severe sepsis not in septic shock , use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days . These findings do not support the use of hydrocortisone in these patients . Trial Registration clinical trials.gov Identifier : NCT00670254 |
754 | 24,880,031 | Statins had uncertain effects on stroke ( 5 studies , 8658 participants ; RR 0.62 , 95 % CI 0.35 to 1.12).Potential harms from statin therapy were limited by lack of systematic reporting and were uncertain in analyses that had few events : elevated creatine kinase ( 7 studies , 4514 participants ; RR 0.84 , 95 % CI 0.20 to 3.48 ) , liver function abnormalities ( 7 studies , RR 0.76 , 95 % CI 0.39 to 1.50 ) , withdrawal due to adverse events ( 13 studies , 4219 participants ; RR 1.16 , 95 % CI 0.84 to 1.60 ) , and cancer ( 2 studies , 5581 participants ; RR 1.03 , 95 % CI 0.82 to 130).Statins had uncertain effects on progression of CKD .
Statins clearly reduced risks of death , major cardiovascular events , and MI in people with CKD who did not have CVD at baseline ( primary prevention ) .
Statins consistently lower death and major cardiovascular events by 20 % in people with CKD not requiring dialysis .
Statin-related effects on stroke and kidney function were found to be uncertain and adverse effects of treatment are incompletely understood .
Statins have an important role in primary prevention of cardiovascular events and mortality in people who have CKD | BACKGROUND Cardiovascular disease ( CVD ) is the most frequent cause of death in people with early stages of chronic kidney disease ( CKD ) , for whom the absolute risk of cardiovascular events is similar to people who have existing coronary artery disease .
OBJECTIVES To evaluate the benefits ( such as reductions in all-cause and cardiovascular mortality , major cardiovascular events , MI and stroke ; and slow progression of CKD to end-stage kidney disease ( ESKD ) ) and harms ( muscle and liver dysfunction , withdrawal , and cancer ) of statins compared with placebo , no treatment , st and ard care or another statin in adults with CKD who were not on dialysis . | Background — Statins reduce the rate of major cardiovascular events in high-risk patients , but their potential benefit as treatment for heart failure ( HF ) is less clear . Methods and Results — Patients ( n=10 001 ) with stable coronary disease were r and omized to treatment with atorvastatin 80 or 10 mg/d and followed up for a median of 4.9 years . A history of HF was present in 7.8 % of patients . A known ejection fraction < 30 % and advanced HF were exclusion criteria for the study . A predefined secondary end point of the study was hospitalization for HF . The incidence of hospitalization for HF was 2.4 % in the 80-mg arm and 3.3 % in the 10-mg arm ( hazard ratio , 0.74 ; 95 % confidence interval , 0.59 to 0.94 ; P=0.0116 ) . The treatment effect of the higher dose was more marked in patients with a history of HF : 17.3 % versus 10.6 % in the 10- and 80-mg arms , respectively ( hazard ratio , 0.59 ; 95 % confidence interval , 0.4 to 0.88 ; P=0.009 ) . Among patients without a history of HF , the rates of hospitalization for HF were much lower : 1.8 % in the 80-mg group and 2.0 % in the 10-mg group ( hazard ratio , 0.87 ; 95 % confidence interval , 0.64 to 1.16 ; P=0.34 ) . Only one third of patients hospitalized for HF had evidence of preceding angina or myocardial infa rct ion during the study period . Blood pressure was almost identical during follow-up in the treatment groups . Conclusions — Compared with a lower dose , intensive treatment with atorvastatin in patients with stable coronary disease significantly reduces hospitalizations for HF . In a post hoc analysis , this benefit was observed only in patients with a history of HF . The mechanism accounting for this benefit is unlikely to be due primarily to a reduction in interim coronary events or differences in blood pressure BACKGROUND We previously reported urinary podocytes to be a marker of glomerular injury . The aim of the present study was to determine whether cerivastatin , a newly developed , potent synthetic statin , affects proteinuria and urinary podocyte excretion in patients with chronic glomerulonephritis ( CGN ) . METHODS We r and omly assigned 40 normotensive hypercholesterolemic patients with CGN to receive either cerivastatin 0.15 mg/day ( n=20 ) or placebo ( n=20 ) . Subjects comprised 24 men and 16 women , with a mean age of 40.8+/-14.4 years ; 27 had IgA nephropathy and 13 had non-IgA proliferative glomerulonephritis . Treatment was continued for 6 months . Plasma total cholesterol , HDL-cholesterol , LDL-cholesterol and triglycerides , urinary protein excretion and the number of podocytes were measured before treatment and at 3 and 6 months after treatment . RESULTS After 6 months , a significant reduction in total cholesterol ( P<0.001 ) , LDL-cholesterol ( P<0.001 ) and triglycerides ( P<0.05 ) , and a significant increase in HDL-cholesterol ( P<0.001 ) were observed in the group treated with cerivastatin . Urinary protein excretion decreased from 1.8+/-0.6 to 0.8+/-0.4 g/day , ( P<0.01 ) in this group , and urinary podocyte excretion decreased from 1.6+/-0.6 to 0.9+/-0.4 cells/ml ( P<0.01 ) . However , placebo showed little effect on these lipid levels , urinary protein excretion and urinary podocyte excretion . The differences between the cerivastatin group and the placebo group were significant ( cholesterol , P<0.001 ; LDL-cholesterol , P<0.001 ; triglycerides , P<0.05 ; HDL-cholesterol , P<0.001 ; urinary protein , P<0.01 ; and urinary podocytes , P<0.01 ) . CONCLUSION Statins such as cerivastatin may be beneficial for restoration of injured podocytes in patients with CGN and hypercholesterolaemia BACKGROUND The effects of cholesterol-lowering treatment with statins on mortality and risk of cancer beyond the usual 5 - 6-year trial periods are unknown . We extended post-trial follow-up of participants in the Sc and inavian Simvastatin Survival Study ( 4S ) to investigate cause-specific mortality and incidence of cancer 5 years after closure of the trial . METHODS 4S was a r and omised double-blind trial of simvastatin or placebo in patients with coronary heart disease , serum total cholesterol 5.5 - 8.0 mmol/L , and serum triglycerides 2.5 mmol/L or lower . The double-blind period lasted for a median of 5.4 years ( range for survivors 4.9 - 6.3 ) and ended in 1994 . After the trial , most patients in both groups received open-label lipid-lowering treatment . National registers were used to assess mortality and causes of death and cancer incidence in the original treatment groups for a median total follow-up time of 10.4 years ( range for survivors 9.9 - 11.3 ) . Analysis was by intention to treat . FINDINGS 414 patients originally allocated simvastatin and 468 assigned placebo died during the 10.4-year follow-up ( relative risk 0.85 [ 95 % CI 0.74 - 0.97 ] , p=0.02 ) , a difference largely attributable to lower coronary mortality in the simvastatin group ( 238 vs 300 deaths ; 0.76 [ 0.64 - 0.90 ] , p=0.0018 ) . 85 cancer deaths arose in the simvastatin group versus 100 in the placebo group ( 0.81 [ 0.60 - 1.08 ] , p=0.14 ) , and 227 incident cancers were reported in the simvastin group versus 248 in the placebo group ( 0.88 [ 0.73 - 1.05 ] , p=0.15 ) . Incidence of any specific type of cancer did not rise in the simvastatin group . INTERPRETATION Simvastatin treatment for 5 years in a placebo-controlled trial , followed by open-label statin therapy , was associated with survival benefit over 10 years of follow-up compared with open-label statin therapy for the past 5 years only . No difference was noted in mortality from and incidence of cancer between the original simvastatin group and placebo group BACKGROUND The PREVEND IT investigated whether treatment targeted at lowering urinary albumin excretion ( UAE ) would reduce adverse cardiovascular events . We obtained extended follow-up data to approximately 10 years to investigate the long-term effects of fosinopril 20 mg and pravastatin 40 mg on cardiovascular outcomes in subjects with UAE > 15 mg per 24 hours . METHODS The original PREVEND IT consisted of 864 participants and 839 survivors after 4 years . For every survivor , the primary end point determined by the combined incidence of cardiovascular mortality and hospitalization for cardiovascular morbidity was registered in several national data bases and electronic hospital systems . RESULTS Mean total follow-up of the extended PREVEND IT was 9.5 years ( range 9.4 - 10.7 years ) . Four years of treatment with fosinopril was not associated with a reduction in the primary end point compared with placebo ( hazard ratio 0.87 , 95 % CI 0.61 - 1.24 [ P = .42 ] ) during long-term follow-up . After 9.5 years , subjects with a baseline UAE in the upper quintile ( > 50 mg/24 hours ) had a total event rate of 29.5 % and were at a higher risk for developing cardiovascular disease compared with less UAE ( hazard ratio 2.03 , 95 % CI 1.38 - 2.97 [ P ≤ .01 ] ) . In addition , 4 years of fosinopril treatment result ed in a risk reduction of 45 % ( 95 % CI 6%-75 % [ P = .04 ] ) in this group compared with placebo . Subjects originally assigned to pravastatin had no overall risk reduction in the primary end point ( P = .99 ) . CONCLUSIONS Elevated UAE is associated with increased cardiovascular mortality and morbidity after 9.5 years of follow-up , with a doubling of the risk if the UAE is > 50 mg per 24 hours . In this group , the benefits of 4-year treatment with fosinopril were sustained during posttrial follow-up for cardiovascular mortality and morbidity . We propose that UAE be used to estimate risk in the general population and that large clinical trials be design ed to confirm the hypothesis that angiotensin-converting enzyme-inhibitor treatment may be beneficial in patients with mildly elevated UAE despite the absence of other comorbidities Aims Patients with Type 2 diabetes have an elevated risk of stroke . The role of lipid levels and diabetes‐specific factors in risk prediction of stroke is unclear , and estimates of efficacy of lipid‐lowering therapy vary between trials . We examined predictors of stroke and the effect of atorvastatin on specific stroke subtypes in Type 2 diabetes in the Collaborative Atorvastatin Diabetes Study ( CARDS ) [ a trial of 2838 participants with mean low‐density lipoprotein cholesterol < 4.14 mmol/l , no history of macrovascular disease and r and omized to atorvastatin 10 mg daily or placebo ] Background —Therapeutic decisions regarding pharmacological therapy should be based on safety and tolerability as well as efficacy data . Clinical trials design ed to assess efficacy are often insufficiently powered to generate reliable safety data . Methods and Results —The West of Scotl and Coronary Prevention Study ( WOSCOPS ) , the Cholesterol and Recurrent Events ( CARE ) , and Long-term Intervention with Pravastatin in Ischemic Disease ( LIPID ) studies collectively accumulated > 112 000 person-years of exposure in double-blind r and omized trials comparing placebo and pravastatin ( 40 mg once daily ) . During 5 years of exposure , the incidence of fatal and nonfatal cancers was similar between pravastatin and placebo groups . No differences in noncardiovascular serious adverse events were detected . With > 243 000 blood sample analyses , the percentage of patients with any abnormal liver function test after baseline sampling was similar ( > 3 × the upper limit of normal for alanine aminotransferase : 128 [ 1.4 % ] versus 131 [ 1.4 % ] patients for pravastatin versus placebo , respectively ) . Study medication was withdrawn in 3 pravastatin and 7 placebo patients due to creatine phosphokinase elevations ; no cases of mild or severe myopathy were reported . A Cox regression model considering treatment group , age , diabetes , smoking , whether primary or secondary prevention study , and cardiovascular serious adverse events indicates that the likelihood of discontinuing pravastatin was less than placebo . Conclusions —This prospect i ve analysis indicates that during prolonged exposure , 40 mg of pravastatin is well tolerated , with no excess of noncardiovascular serious adverse events , including liver function abnormalities and laboratory and clinical evidence for myositis . These extensive safety and tolerability data provide important information for therapeutic decisions regarding this pharmacological agent BACKGROUND Although patients with chronic kidney disease ( CKD ) are at increased risk of cardiovascular disease ( CVD ) , the roles of lipid-modifying therapies in decreasing CVD risk are unclear . Our aim is to compare the effects of statin and fibrate therapy on arterial function as a risk marker of CVD . STUDY DESIGN Double-blind , r and omized , placebo-controlled , parallel-group study . SETTING & PARTICIPANTS Ambulatory patients with stages 3 to 5 CKD . INTERVENTION 6 weeks of atorvastatin , 40 mg/d , or gemfibrozil , 600 mg twice daily , with placebo . OUTCOMES & MEASUREMENTS Primary outcome was arterial function assessed by means of endothelial-dependent flow-mediated dilatation ( FMD ) and small-artery compliance ( C2 ) . Secondary outcomes included endothelial-independent glyceryl trinitrate-mediated dilatation ( GTNMD ) , large-artery compliance ( C1 ) , and levels of lipids , lipoproteins , and oxidized low-density lipoprotein , as well as markers of insulin resistance and inflammation . RESULTS Compared with placebo , atorvastatin significantly decreased low-density lipoprotein ( -52 % ) , triglyceride ( -30 % ) , and oxidized low-density lipoprotein levels ( -41 % ; P < 0.0001 ) . Gemfibrozil significantly decreased triglyceride levels ( -40 % ) and increased high-density lipoprotein levels ( + 20 % ; P < 0.0001 ) . Neither atorvastatin nor gemfibrozil had a significant effect on markers of insulin resistance or inflammation . There was no significant change in FMD , GTNMD , or C1 with either atorvastatin or gemfibrozil . There was improvement in C2 with atorvastatin ( + 1.1 mL/mm Hg x 100 ) compared with placebo ( P = 0.024 ) , but not with gemfibrozil compared with placebo . LIMITATIONS Small sample size leading to inadequate power , short duration of therapy , and use of a heterogeneous group of patients with CKD and dialysis patients . CONCLUSION In patients with advanced CKD , atorvastatin is associated with improvement in dyslipidemia and small-artery stiffness , but not endothelial function . Gemfibrozil improves dyslipidemia , but has no effect on arterial function Objective . Autosomal dominant polycystic kidney disease ( ADPKD ) is progressive , result ing in end-stage kidney failure in most patients . Experimental and clinical studies have suggested that statins may slow the progression of chronic kidney disease in general and ADPKD specifically . Material and methods . This r and omized open-label clinical trial was conducted to assess the effect of pravastatin 20 mg on kidney function and urinary protein excretion in patients with ADPKD . Sixty patients were initially recruited but 49 of these received either pravastatin 20 mg or no treatment for 2 years . Trial visits were conducted every 3 months , assessing kidney function by estimated glomerular filtration rate and 24 h urine creatinine clearance and urinary protein excretion . Results . There were no significant ( p > 0.05 ) changes in markers of kidney function or urinary protein excretion between groups over the 2 years despite a significant fall in total serum cholesterol in pravastatin-treated patients ( p = 0.029 ) . Conclusion . This trial found that taking 20 mg pravastatin for 2 years had no significant effect on kidney function or urinary protein excretion in patients with ADPKD . The lack of statistical power limits the external validity of these findings . A larger , longer duration study using a higher dose of a more potent statin is required The purpose of this 20-week , open-label , r and omized clinical trial was to evaluate the effect of rosuvastatin on fasting serum lipids and lipoproteins , high-sensitivity C-reactive protein ( hs-CRP ) , and the glomerular filtration rate ( GFR ) in 91 patients with chronic kidney disease . Patients were r and omized to rosuvastatin 10 mg/day ( n = 48 ) or to no lipid-lowering treatment ( n = 43 ) for 20 weeks . In contrast to patients not receiving rosuvastatin , patients receiving rosuvastatin tended to derive more favorable improvements from baseline values in low-density lipoprotein cholesterol ( -43 % , p < 0.001 , vs 7 % , p = NS ; p < 0.001 for change with rosuvastatin treatment vs change with no antilipemic treatment ) , hs-CRP ( -47 % , p < 0.001 , vs 7 % , p = NS ; p < 0.001 for change with rosuvastatin treatment vs change with no antilipemic treatment ) , and GFR ( 11 % , p < 0.05 , vs 4 % , p = NS ; p = NS for change with rosuvastatin treatment vs change with no antilipemic treatment ) Background Patients with chronic kidney disease ( CKD ) are at a greatly increased risk of developing cardiovascular disease . Recently developed guidelines address multiple risk factors and life-style interventions . However , in current practice few patients reach their targets . A multifactorial approach with the aid of nurse practitioners was effective in achieving treatment goals and reducing vascular events in patients with diabetes mellitus and in patients with heart failure . We propose that this also holds for the CKD population . Design MASTERPLAN is a multicenter r and omized controlled clinical trial design ed to evaluate whether a multifactorial approach with the aid of nurse-practicioners reduces cardiovascular risk in patients with CKD . Approximately 800 patients with a creatinine clearance ( estimated by Cockcroft-Gault ) between 20 to 70 ml/min , will be included . To all patients the same set of guidelines will be applied and specific cardioprotective medication will be prescribed . In the intervention group the nurse practitioner will provide lifestyle advice and actively address treatment goals . Follow-up will be five years . Primary endpoint is the composite of myocardial infa rct ion , stroke and cardiovascular mortality . Secondary endpoints are cardiovascular morbidity , overall mortality , decline of renal function , change in markers of vascular damage and change in quality of life . Enrollment has started in April 2004 and the study is on track with 700 patients included on October 15th , 2005 . This article describes the design of the MASTERPLAN study BACKGROUND Patients with chronic kidney disease ( CKD ) have an increased risk of cardiovascular disease ( CVD ) . Preliminary evidence suggests a role for global DNA hypomethylation in the pathogenesis of atherosclerotic complications in CKD . The aims of this study in patients with stage 2 - 4 CKD were ( 1 ) to assess the association between renal function and DNA methylation , ( 2 ) to assess the association between DNA methylation and two markers of atherosclerosis [ common carotid intima-media thickness ( CCA-IMT ) ] and brachial artery endothelium-dependent , flow-mediated dilatation ( BA-FMD ) and ( 3 ) to examine the effect of a multi-step treatment strategy on DNA methylation . METHODS In the Anti-Oxidant Therapy In Chronic Renal Insufficiency study ( ATIC- study ) , 93 patients with stage 2 - 4 CKD were included . In a r and omized , double-blind , placebo-controlled design , the treatment group received pravastatin to which vitamin E was added after 6 months and homocysteine-lowering B-vitamin therapy after another 6 months . DNA methylation was assessed using t and em mass spectrometry . CCA-IMT and BA-FMD were assessed using B-mode ultrasonography . RESULTS At baseline , global DNA methylation was not associated with the estimated glomerular filtration rate ( P = 0.32 ) or with CCA-IMT ( P = 0.62 ) or BA-FMD ( P = 0.51 ) . No effect of the treatment strategy including B-vitamin on global DNA methylation was found either in the total study group or within separate strata of homocysteine concentration and renal function . CONCLUSION In patients with stage 2 - 4 CKD , global DNA methylation is not associated with renal function or with CCA-IMT or BA-FMD . A treatment strategy that includes B-vitamins did not alter global DNA methylation in these patients . These data do not support the role of DNA hypomethylation in CKD-associated vascular disease in patients with stage 2 - 4 CKD Background —Leptin plays a role in fat metabolism and correlates with insulin resistance and other markers of the metabolic syndrome , independent of total adiposity . Therefore , we hypothesized that raised leptin levels may identify men at increased risk of a coronary event in the West of Scotl and Coronary Prevention Study ( WOSCOPS ) . Methods and Results —Plasma leptin levels were measured at baseline in 377 men ( cases ) who subsequently experienced a coronary event and in 783 men ( controls ) who remained free of an event during the 5-year follow-up period of the study . Controls were matched to cases on the basis of age and smoking history and were representative of the entire WOSCOPS cohort . Leptin levels were significantly higher in cases than controls ( 5.87±2.04 ng/mL versus 5.04±2.09 ng/mL , P < 0.001 ) . In univariate analysis , for each 1 SD increase in leptin , the relative risk ( RR ) of an event increased by 1.25 ( 95 % confidence interval [ CI ] , 1.10 to 1.43;P < 0.001 ) . There was minimal change in this RR with correction for body mass index ( RR , 1.24 ; 95 % CI , 1.06 to 1.45;P = 0.006 ) or with further correction for classic risk factors , including age , lipids , and systolic blood pressure ( RR , 1.20 ; 95 % CI , 1.02 to 1.42;P = 0.03 ) . Leptin correlated with C-reactive protein ( r = 0.24 , P < 0.001 ) and , even with this variable added to the model , leptin retained significance as a predictor of coronary events ( RR , 1.18 ; 95 % CI , 1.00 to 1.39;P = 0.05 ) at the expense of C-reactive protein . Conclusions —We show , for the first time , in a large prospect i ve study that leptin is a novel , independent risk factor for coronary heart disease BACKGROUND Cardiovascular mortality is extremely high in end-stage renal disease . Cardiovascular mortality risk also is increased in selected ( high-risk ) individuals with mild to moderate impairment of renal function . It is not clear whether a similar association exists in the general population and , if so , through what mechanisms . We investigated the association of renal function with all-cause and cardiovascular mortality in a population -based cohort and explored potential mechanisms underlying any such relationship . METHODS An age- , sex- , and glucose-tolerance-stratified sample ( N = 631 ) of a population -based cohort aged 50 to 75 years was followed prospect ively . After up to 10.2 years of follow-up , 117 subjects had died ( 50 of cardiovascular causes ) . At baseline , renal function was estimated by the serum creatinine level , the Cockcroft-Gault formula and Levey 's equation . RESULTS At baseline , the mean age was 64 + /- 7 years , 48 % were men , 55 % had hypertension , and 27 % ( by design ) had type 2 diabetes . Serum creatinine was 91.7 + /- 19.0 micromol/L ; creatinine clearance as estimated by the Cockroft-Gault formula was 72.5 + /- 13.7 mL/min/1.73 m(2 ) , and the glomerular filtration rate ( GFR ) estimated by Levey 's equation was 67.8 + /- 12.1 mL/min/1.73 m(2 ) . Renal function was inversely associated with all-cause and with cardiovascular mortality . Relative risks ( 95 % confidence intervals ) were 1.08 ( 1.04 to 1.13 ) and 1.11 ( 1.07 to 1.16 ) per 5 micromol/L increase of serum creatinine ; 1.07 ( 0.98 to 1.17 ) and 1.15 ( 1.01 to 1.31 ) for each decrease of 5 mL/min/1.73 m(2 ) creatinine clearance ; and 1.15 ( 1.05 to 1.26 ) and 1.26 ( 1.12 to 1.42 ) for each decrease of 5 mL/min/1.73 m(2 ) of GFR . These associations remained after adjusting for age , sex , glucose tolerance status , hypertension , prior cardiovascular disease , low-density lipoprotein cholesterol , homocysteine , (micro)albuminuria , von Willebr and factor , soluble vascular adhesion molecule-1 and C-reactive protein . Analyses in diabetic and hypertensive subjects gave similar results . CONCLUSION Mild to moderate loss of renal function is strongly associated with an increased risk of cardiovascular mortality . The mechanism behind this association is unclear but does not appear to involve common risk factors such as hypertension , diabetes or hyperhomocysteinemia . Estimation of renal function by relatively simple methods therefore may be a valuable tool for cardiovascular risk assessment over and above that provided by conventional risk factors . Our results were obtained in a general middle-aged to elderly population , and thus have broad applicability BACKGROUND Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events . Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol , we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment . METHODS We r and omly assigned 17,802 apparently healthy men and women with low-density lipoprotein ( LDL ) cholesterol levels of less than 130 mg per deciliter ( 3.4 mmol per liter ) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin , 20 mg daily , or placebo and followed them for the occurrence of the combined primary end point of myocardial infa rct ion , stroke , arterial revascularization , hospitalization for unstable angina , or death from cardiovascular causes . RESULTS The trial was stopped after a median follow-up of 1.9 years ( maximum , 5.0 ) . Rosuvastatin reduced LDL cholesterol levels by 50 % and high-sensitivity C-reactive protein levels by 37 % . The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups , respectively ( hazard ratio for rosuvastatin , 0.56 ; 95 % confidence interval [ CI ] , 0.46 to 0.69 ; P<0.00001 ) , with corresponding rates of 0.17 and 0.37 for myocardial infa rct ion ( hazard ratio , 0.46 ; 95 % CI , 0.30 to 0.70 ; P=0.0002 ) , 0.18 and 0.34 for stroke ( hazard ratio , 0.52 ; 95 % CI , 0.34 to 0.79 ; P=0.002 ) , 0.41 and 0.77 for revascularization or unstable angina ( hazard ratio , 0.53 ; 95 % CI , 0.40 to 0.70 ; P<0.00001 ) , 0.45 and 0.85 for the combined end point of myocardial infa rct ion , stroke , or death from cardiovascular causes ( hazard ratio , 0.53 ; 95 % CI , 0.40 to 0.69 ; P<0.00001 ) , and 1.00 and 1.25 for death from any cause ( hazard ratio , 0.80 ; 95 % CI , 0.67 to 0.97 ; P=0.02 ) . Consistent effects were observed in all subgroups evaluated . The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes . CONCLUSIONS In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels , rosuvastatin significantly reduced the incidence of major cardiovascular events . ( Clinical Trials.gov number , NCT00239681 . The Sc and inavian Simvastatin Survival Study ( 4S ) and other r and omized clinical trials have demonstrated that cholesterol-lowering treatment with statins improves prognosis in patients with coronary atherosclerosis compared with placebo . The effect of therapy with statins beyond the typical 5 to 6 years ' duration of the trials , in particular regarding the risk of cancer , has not been investigated . This study examines the long-term effects of simvastatin for up to 8 years on cause-specific mortality in patients with coronary heart disease ( CHD ) . We performed an observational , government registry-based study of mortality in the groups originally r and omized to simvastatin or placebo in the 4S over an additional 2-year follow-up period , so that the median total follow-up period was 7.4 years ( range 6.9 to 8.3 in surviving patients ) . R and omization took place at outpatient clinics at 94 clinical centers in Denmark , Finl and , Icel and , Norway , and Sweden from 1988 to 1989 . Of 4,444 patients with CHD , 2,223 and 2,221 were r and omized to treatment with placebo or simvastatin therapy , respectively . Patients received treatment with simvastatin , starting at 20 mg/day , with titration to 40 mg/day at 12 or 24 weeks if total cholesterol was > 5.2 mmol/L ( 200 mg/dl ) , or placebo . After the double-blind period , most patients in both treatment groups received simvastatin as open-label prescription . Of the 1,967 patients originally treated with placebo and surviving the double-blind period , 97 ( 4.9 % ) died during the following 2 years . In the group r and omized to simvastatin the corresponding number was 74 of the 2 , 039 survivors ( 3.6 % ) . Adding these deaths to those occurring during the original trial , the total was 353 ( 15.9 % ) and 256 ( 11.5 % ) deaths in the groups originally r and omized to placebo and simvastatin , respectively . The relative risk was 0.70 ( 95 % confidence interval 0 . 60 to 0.82 , p = 0.00002 ) . The total number of cancer deaths was 68 ( 3.1 % ) in the placebo group and 52 ( 2.3 % ) in the simvastatin group ( relative risk 0.73 , 95 % confidence interval 0.51 to 0.05 , p = 0 . 087 ) , and the numbers of noncardiovascular and other deaths were similar in both groups . We therefore conclude that treatment with simvastatin for up to 8 years in patients with CHD is safe and yields continued survival benefit BACKGROUND Chronic kidney disease ( CKD ) is associated with an increased risk of incident cardiovascular disease ( CVD ) ; however , the role of statins for the primary prevention of acute cardiovascular events in patients with CKD and the effect of statins on kidney function loss in persons without prevalent CVD have not been studied . STUDY DESIGN Post hoc analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study . SETTING & PARTICIPANTS Multicenter , r and omized , double-blind , placebo-controlled trial of 5,608 men and 997 women without CVD r and omly assigned to treatment with lovastatin or placebo . INTERVENTION Placebo or lovastatin , 20 mg/d . OUTCOMES & MEASUREMENTS First major acute cardiovascular event in participants with mild CKD and kidney function loss in persons with or without CKD . Estimated glomerular filtration rate was calculated using the 4-variable Modification of Diet in Renal Disease Study equation . RESULTS At baseline , mean estimated glomerular filtration rate in participants with CKD ( n = 304 ) was 53.0 + /- 6.0 mL/min/1.73 m(2 ) . After an average follow-up of 5.3 + /- 0.8 years , the incidence of a fatal and nonfatal CVD event was lower in participants with CKD receiving lovastatin than in those receiving placebo ( adjusted relative risk [ RR ] , 0.31 ; 95 % CI , 0.13 - 0.72 ; P = 0.01 ) . Tests for interaction suggested that the benefit of lovastatin was independent of the presence of CKD . Lovastatin did not reduce the annualized mean decrease in estimated glomerular filtration rate ( -1.3 + /- 0.07 vs -1.4 + /- 0.07 mL/min/1.73 m(2)/y , respectively ; P = 0.1 ) or the frequency of a > or = 25 % decrease in kidney function ( adjusted RR , 1.10 ; 95 % CI , 0.96 - 1.28 ; P = 0.2 ) or incident CKD ( adjusted RR , 1.04 ; 95 % CI , 0.86 - 1.27 ; P = 0.6 ) . LIMITATIONS Unable to determine the cause and duration of kidney disease , and information regarding proteinuria was not available . CONCLUSIONS Lovastatin is effective for the primary prevention of CVD in patients with CKD , but is not effective in decreasing kidney function loss in persons with no CVD Background Patients with end-stage renal disease ( ESRD ) are at high risk of cardiovascular events . Multiple risk factors for atherosclerosis are present in ESRD and may contribute to the increased risk of cardiovascular mortality in this population . In contrast to patients with normal renal function , the benefits of modifying lipid levels on cardiovascular outcomes in patients with ESRD on haemodialysis have yet to be confirmed in large prospect i ve r and omised trials . A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis : an Assessment of survival and cardiovascular events ( AURORA ) will be the first large-scale international trial to assess the effects of statin therapy on cardiovascular morbidity and mortality in ESRD patients on chronic haemodialysis . Methods More than 2,750 ESRD patients who have been receiving chronic haemodialysis treatment for at least 3 months have been r and omised ( 1:1 ) , irrespective of baseline lipid levels , to treatment with rosuvastatin 10 mg or placebo . The primary study endpoint is the time to a major cardiovascular event ( first occurrence of cardiovascular death , non-fatal myocardial infa rct ion or non-fatal stroke ) . Secondary endpoints include all-cause mortality , major cardiovascular event-free survival time , time to cardiovascular death , time to non-cardiovascular death , cardiovascular interventions , tolerability of treatment and health economic costs per life-year saved . Study medication will be given until 620 subjects have experienced a major cardiovascular event . Conclusion Our hypothesis is that results from AURORA will establish the clinical efficacy and tolerability of rosuvastatin in patients with ESRD receiving chronic haemodialysis and guide the optimal management of this exp and ing population AIMS To analyse ( 1 ) the prognostic importance of clinical findings and lipids in patients with a previous myocardial infa rct ion and ( 2 ) the relative and absolute benefit of simvastatin in patients at low , medium and high predicted risk . METHODS The 4S was a double-blind , r and omized , clinical trial of long-term treatment with simvastatin or matching placebo in patients with myocardial infa rct ion or angina pectoris , serum total cholesterol 5.5 - 8.0 mmol x l(-1 ) , and serum triglycerides < or=2.5 mmol x l(-1 ) . The present study only deals with those 3525 patients who had a previous myocardial infa rct ion . End-points comprised coronary death , definite and probable hospital verified myocardial infa rct ion , and resuscitated cardiac arrest . Because there were few women the primary analyses were performed among men . RESULTS A Cox model analysis in the placebo group identified the following independent predictors of coronary events : a history of hypertension ( P=0.023 ) , diabetes ( P=0.0001 ) , smoking after the myocardial infa rct ion ( P=0.010 ) , total cholesterol ( P=0.020 ) , and HDL cholesterol ( P=0.062 ) . The relative reduction of risk by simvastatin treatment in patients at low , medium and high predicted risk was 38 % , 39 % and 42 % , respectively , but the corresponding absolute benefit per 100 patients treated for 6 years increased from 7.9 to 16.2 . CONCLUSION In addition to serum lipids , clinical variables contributed significantly to prediction . The relative benefit from simvastatin treatment was independent of predicted risk , but the absolute benefit increased from low to high risk BASIS Hyperlipidemia associated to nephrotic syndrome has been involved in the deterioration of the renal function in these patients . The reduction in the synthesis of cholesterol with pravastatin , an hydrophilic inhibitor of such synthesis , may improve both the dyslipemia , the renal function and the proteinuria . METHODS We conducted a controlled open r and omized study in 16 patients with proteinuria greater than 2 g/day , creatinine clearance greater than 0.5 ml/s ( 30 ml/min ) and hypercholesterolemia with LDL cholesterol greater than 4.9 mmol/l ( 190 mg/dl ) distributed in two groups . One of these groups received hypolipemiant dietetic treatment and 20 - 40 mg of pravastatin and the other group , only the dietetic treatment . RESULTS The patients receiving pravastatin showed a 27 % decrease in total plasmatic cholesterol , compared to a 6.7 % in the control group ( p < 0.01 ) . This decrease was more evident in the LDL cholesterol fraction ( 44 vs 9 % ; p < 0.01 ) . No significant modifications were observed in the HDL cholesterol fraction , triglycerides , renal function or proteinuria . Neither clinical nor enzymatiz adverse effects from hepatic or muscular origin were observed In this study 43 patients with idiopathic nephrotic syndrome were r and omly distributed into 2 age- and sex-matched groups . The first group was given fluvastatin while the second was used as control . The cases in the 2 groups were evaluated clinical ly , biochemically ( creatinine clearance , albumin , 24-hour proteinuria , and lipogram ) , neurologically , and histopathologically ( examination of renal biopsies obtained basally and after 1 year of treatment with fluvastatin ) . In the fluvastatin-treated group but not in the control group , we observed a significant reduction in cholesterol , low-density lipoprotein , and triglyceride . Clinical and laboratory assessment showed satisfactory tolerance of the drug by the patients . Proteinuria , serum albumin and creatinine clearance values were significantly better in the statin-treated patients . There was no difference in glomerular sclerosis between the 2 groups while interstitial fibrosis and renal fat deposits were less in the statin-treated group . The reduction in renal fat deposits in the statin-treated group was highly significant , while that of interstitial fibrosis was not . We conclude that : ( 1 ) statin can be safely and effectively used in the treatment of dyslipidemia in patients with persistent idiopathic nephrotic syndrome ; ( 2 ) control of dyslipidemia in nephrotic patients is associated with better control of proteinuria and creatinine clearance ; ( 3 ) statin treatment may cause regression of renal fat deposits in patients with nephrotic syndrome , and ( 4 ) longer term studies are still required to study further possible beneficial effects on renal histology and disease progression Mild renal impairment is an important risk factor for late cardiovascular complications . This sub study of the Lescol Intervention Prevention Study ( LIPS ) assessed the effect of fluvastatin on outcome of patients who had renal dysfunction and those who did not . Complete data for creatinine clearance calculation ( Cockcroft-Gault formula ) were available for 1,558 patients ( 92.9 % of the LIPS population ) . Patients were r and omized to fluvastatin or placebo after successful completion of a first percutaneous coronary intervention . Follow-up time was 3 to 4 years . The effect of baseline creatinine clearance on coronary atherosclerotic events ( cardiac death , nonfatal myocardial infa rct ion , and coronary re interventions not related to restenosis ) was evaluated . Baseline creatinine clearance ( logarithmic transformation ) was inversely associated with an incidence of adverse events among patients who received placebo ( hazard ratio 0.99 , 95 % confidence interval 0.982 to 0.998 , p = 0.01 ) . However , no association was noted between creatinine clearance and the incidence of adverse events among patients who received fluvastatin ( hazard ratio 1.0 , 95 % confidence interval 0.99 to 1.0 , p = 0.63 ) . No further deterioration in creatinine clearance was observed during follow-up , regardless of baseline renal function or allocated treatment . Occurrence of adverse events was not related to changes in renal function during follow-up . Fluvastatin therapy markedly decreased the risk of coronary atherosclerotic events after percutaneous intervention in patients who had lower values of creatinine clearance at baseline . The benefit of fluvastatin was unrelated to any effect on renal function BACKGROUND The effect of atorvastatin on kidney function was assessed in patients with stages 2 - 4 chronic kidney disease . METHODS We conducted a r and omised , double-blind , placebo-controlled trial in chronic kidney disease clinics in Northern Tasmania and enrolled 132 patients with serum creatinine levels > 120 μmol/l , not taking lipid-lowering therapy and at all levels of proteinuria and serum cholesterol . Patients were r and omly assigned to receive either 10 mg of atorvastatin/day ( 64 ) or placebo ( 68 ) and were followed with trial visits 3-monthly for a mean of 2.5 yrs . The primary outcome was the rate of both MDRD eGFR and Cockcroft-Gault creatinine clearance ( C-G CrCl ) decline . Analysis was based on intention to treat and included all patients that had at least one follow-up visit . RESULTS The rate of MDRD eGFR decline was 29 % lower ; 1.04 ± 3.84 vs. 1.47 ± 3.74 ml/min/1.73 m(2)/yr ( P=0.53 ) , and the C-G CrCl was 20 % lower ; 1.88 ± 5.07 vs. 2.36 ± 4.61 ml/min/1.73 m(2)/yr ( P=0.58 ) in atorvastatin-treated , compared with placebo-treated patients . Although blood pressure decreased in both atorvastatin and placebo-treated groups there were no differences between groups . In addition , there was no difference in concomitant medication intake including angiotensin converting enzyme inhibitors and angiotensin receptor blockers between groups . CONCLUSIONS There was a trend toward a slower eGFR decline in the atorvastatin-treated group that did not reach statistical significance . This may have been due to the lack of power of the study . However , atorvastatin may have a renoprotective effect in those patients with chronic kidney disease and cardiovascular disease . This needs to be assessed in further studies Moderate to severe chronic kidney disease ( CKD ) is associated with increased cardiovascular risk . Usually nephrologists are primarily responsible for the care of CKD patients . However , in many cases treatment goals , as formulated in guidelines , are not met . The addition of a nurse practitioner might improve the quality of care . The Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners ( MASTERPLAN ) study is a r and omized controlled multicenter trial , aim ed at investigating whether a multifactorial approach in patients with moderate to severe CKD ( stage 3 and 4 ) to achieving treatment goals using both a polydrug strategy and lifestyle treatment either with or without the addition of a nurse practitioner will reduce cardiovascular risk and slow the decline of kidney function . Patients ( n=793 ) have been r and omized to nurse care or physician care . In the nurse-care arm of the study , nurse practitioners use flowcharts to address risk factors requiring drug and /or lifestyle modification . They have been trained to coach patients by motivational interviewing with the aim of improving patient self-management . At baseline , both treatment groups show equal distributions with regard to key variables in the study . Moreover , in only 1 patient were all risk factors within the limits as defined in various guidelines , which underscores the relevance of our initiative OBJECTIVE This study aims to establish the benefits of lowering cholesterol in diabetic patients with well-controlled hypertension and average/below-average cholesterol concentrations , but without established coronary disease . RESEARCH DESIGN AND METHODS In the lipid-lowering arm of the Anglo-Sc and inavian Cardiac Outcomes Trial ( ASCOT-LLA ) , 10,305 hypertensive patients with no history of coronary heart disease ( CHD ) but at least three cardiovascular risk factors were r and omly assigned to receive 10 mg atorvastatin or placebo . Effects on total cardiovascular outcomes in 2,532 patients who had type 2 diabetes at r and omization were compared . RESULTS During a median follow-up of 3.3 years , concentrations of total and LDL cholesterol among diabetic participants included in ASCOT-LLA were approximately 1 mmol/l lower in those allocated atorvastatin compared with placebo . There were 116 ( 9.2 % ) major cardiovascular events or procedures in the atorvastatin group and 151 ( 11.9 % ) events in the placebo group ( hazard ratio 0.77 , 95 % CI 0.61 - 0.98 ; P = 0.036 ) . For the individual components of this composite end point , the number of events occurring in the diabetes subgroup was small . Therefore , although fewer coronary events ( 0.84 , 0.55 - 1.29 ; P = 0.14 ) and strokes ( 0.67 , 0.41 - 1.09 ; P = 0.66 ) were observed among the patients allocated atorvastatin , these reductions were not statistically significant . CONCLUSIONS Atorvastatin significantly reduced the risk of major cardiovascular events and procedures among diabetic patients with well-controlled hypertension and without a history of CHD or markedly elevated cholesterol concentrations . The proportional reduction in risk was similar to that among participants who did not have diagnosed diabetes . Allocation to atorvastatin prevented approximately 9 diabetic participants from suffering a first major cardiovascular event or procedure for every 1,000 treated for 1 year OBJECTIVES The goal of this study was to determine whether the level of kidney function is an independent risk factor for atherosclerotic cardiovascular disease ( ASCVD ) outcomes in the Atherosclerosis Risk in Communities ( ARIC ) study , a prospect i ve cohort study of subjects aged 45 to 64 years . BACKGROUND The level of kidney function is now recognized as a risk factor for ASCVD outcomes in patients at high risk for ASCVD , but it remains unknown whether the level of kidney function is a risk factor for ASCVD outcomes in the community . METHODS Cox proportional-hazards regression was used to evaluate the association of glomerular filtration rate ( GFR ) with ASCVD after adjustment for the major ASCVD risk factors in 15,350 subjects . We search ed for nonlinear relationships between GFR and ASCVD . RESULTS During a mean follow-up time of 6.2 years , 965 ( 6.3 % ) of subjects had ASCVD events . Subjects with GFR of 15 to 59 ml/min/1.73 m(2 ) ( n = 444 , hazard ratio 1.38 [ 1.02 , 1.87 ] ) and 60 to 89 ml/min/1.73 m(2 ) ( n = 7,665 , hazard ratio 1.16 [ 1.00 , 1.34 ] ) had an increased adjusted risk of ASCVD compared with subjects with GFR of 90 to 150 ml/min/1.73 m(2 ) . Each 10 ml/min/1.73 m(2 ) lower GFR was associated with an adjusted hazard ratio of 1.05 ( 1.02 , 1.09 ) , 1.07 ( 1.01 , 1.12 ) , and 1.06 ( 0.99 , 1.13 ) for ASCVD , de novo ASCVD , and recurrent ASCVD , respectively . A nonlinear model did not fit the data better than a linear model . CONCLUSIONS The level of GFR is an independent risk factor for ASCVD and de novo ASCVD in the ARIC study Background The high incidence of cardiovascular disease in patients with end stage renal disease ( ESRD ) is related to the accumulation of uremic toxins in the middle and large-middle molecular weight range . As online hemodiafiltration ( HDF ) removes these molecules more effectively than st and ard hemodialysis ( HD ) , it has been suggested that online HDF improves survival and cardiovascular outcome . Thus far , no conclusive data of HDF on target organ damage and cardiovascular morbidity and mortality are available . Therefore , the CONvective TRAnsport STudy ( CONTRAST ) has been initiated . Methods CONTRAST is a Dutch multi-center r and omised controlled trial . In this trial , approximately 800 chronic hemodialysis patients will be r and omised between online HDF and low-flux HD , and followed for three years . The primary endpoint is all cause mortality . The main secondary outcome variables are fatal and non-fatal cardiovascular events . Conclusion The study is design ed to provide conclusive evidence whether online HDF leads to a lower mortality and less cardiovascular events as compared to st and ard HD Proteinuria is an important risk factor for cardiovascular and renal morbidity and mortality . The effects of 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitor ( statin ) therapy on proteinuria in normolipidemic patients with well-controlled hypertension have not been studied . A total of 63 normolipidemic ( total cholesterol < 240 mg/dL ) and proteinuric ( 300 to 3000 mg/d ) patients with well-controlled blood pressure ( < 140/90 mm Hg ) were r and omized to receive either placebo ( n=32 ) or pravastatin ( 10 mg/d ; n=31 ) after a 3-month placebo period . Pravastatin lowered proteinuria after 6 months by 54 % ( P < 0.0001 ) . Creatinine clearance was stable throughout the study in the 2 groups . Despite unchanged plasma endothelin-1 levels throughout the study , urinary excretion of the peptide was decreased and significantly correlated with improvement in urinary protein excretion in pravastatin-treated patients ( r = 0.64 , P = 0.001 ) . The urinary excretion of retinol-binding protein decreased after pravastatin administration , probably reflecting an improvement in tubular function . In contrast , the urinary excretion of IgG did not change significantly throughout the study in either group . Multivariate analysis revealed that proteinuria was only significantly correlated with statin use ( P < 0.0001 , R2= 0.66 ) . Linear regression analysis in the statin-treated group did not show any correlation between changes in lipid profiles and proteinuria regression . Thus , in addition to their primary function of antilipidemia , the addition of pravastatin to treatment for well-controlled hypertension may have an additive effect on reducing proteinuria independent of hemodynamics and lipid-lowering effects , possibly through inhibiting renal endothelin-1 synthesis and improving tubular function BACKGROUND The aim of this study is to assess the cost-effectiveness of the lipid-lowering arm of the Anglo-Sc and inavian Cardiac Outcomes Trial ( ASCOT-LLA ) where patients from seven countries with hypertension and no history of coronary heart disease ( CHD ) were r and omized to receive 10 mg atorvastatin or placebo . DESIGN Economic analysis of a r and omized controlled trial . METHODS Data on re source use were aggregated for all patients during the entire trial period ( median 3.3 years ) and multiplied with unit costs for Sweden and the UK . The total number of cardiovascular events and procedures avoided was used as the measure of effectiveness . RESULTS Patients treated with atorvastatin had an additional net costs of 449 euro ( 4114 SEK ) in Sweden and 414 euro ( 260 pounds sterling ) in the UK , but fewer events per patient ( 0.097 compared to 0.132 ) . The incremental cost-effectiveness ratios were 12673 euro ( 116119 SEK ) and 11693 euro ( 7349 pounds sterling ) per event avoided . CONCLUSION Based on comparisons with the WOSCOPS and 4S studies , atorvastatin at 10 mg to treat patients as in the ASCOT study , appears to be a cost-effective strategy Background —Microalbuminuria is associated with increased risk of cardiovascular events . We assessed whether therapeutic intervention aim ed at lowering urinary albumin excretion would reduce cardiovascular events in microalbuminuric subjects ( 15 to 300 mg/24 hours ) . Methods and Results —From the Prevention of Renal and Vascular Endstage Disease ( PREVEND ) cohort ( n=8592 ) , 1439 subjects fulfilled the inclusion criteria of the PREVEND Intervention Trial ( PREVEND IT ) . Of these subjects , 864 were r and omized to fosinopril 20 mg or matching placebo and to pravastatin 40 mg or matching placebo . The mean follow-up was 46 months , and the primary end point was cardiovascular mortality and hospitalization for cardiovascular morbidity . Mean age was 51±12 years ; 65 % of subjects were male , and 3.4 % had a previous cardiovascular event . Mean cholesterol level was 5.8±1.0 mmol/L , mean systolic/diastolic blood pressure was 130±18/76±10 mm Hg , and median urinary albumin excretion was 22.8 ( 15.8 to 41.3 ) mg/24 hours . The primary end point occurred in 45 subjects ( 5.2 % ) . Fosinopril reduced urinary albumin excretion by 26 % ( P<0.001 ) . Subjects treated with fosinopril showed a 40 % lower incidence of the primary end point ( hazard ratio 0.60 [ 95 % CI 0.33 to 1.10 ] , P=0.098 , log-rank ) . Pravastatin did not reduce urinary albumin excretion , and subjects treated with pravastatin showed a 13 % lower incidence of the primary end point than subjects in the placebo group ( 0.87 [ 0.49 to 1.57 ] , P=0.649 , log-rank ) . Conclusions —In microalbuminuric subjects , treatment with fosinopril had a significant effect on urinary albumin excretion . In addition , fosinopril treatment was associated with a trend in reducing cardiovascular events . Treatment with pravastatin did not result in a significant reduction in urinary albumin excretion or cardiovascular events OBJECTIVE —Rates of cardiovascular disease are highest in the elderly . Lipid-lowering statin therapy reduces the proportional risk as effectively in older patients as in younger individuals ; however , limited data are available for elderly patients with type 2 diabetes . We conducted a post hoc analysis to compare the efficacy and safety of atorvastatin among 1,129 patients aged 65–75 years at r and omization with 1,709 younger patients in the Collaborative Atorvastatin Diabetes Study ( CARDS ) . RESEARCH DESIGN AND METHODS —CARDS was a r and omized placebo-controlled trial of 10 mg/day atorvastatin for primary prevention of cardiovascular disease in patients aged 40–75 years with LDL cholesterol concentrations ≤4.14 mmol/l followed for a median of 3.9 years . The primary end point was time to first occurrence of acute coronary heart disease events , coronary revascularizations , or stroke . RESULTS —Atorvastatin treatment result ed in a 38 % reduction in relative risk ( [ 95 % CI −58 to −8 ] , P = 0.017 ) of first major cardiovascular events in older patients and a 37 % reduction ( [ −57 to −7 ] , P = 0.019 ) in younger patients . Corresponding absolute risk reductions were 3.9 and 2.7 % , respectively ( difference 1.2 % [ 95 % CI −2.8 to 5.3 ] , P = 0.546 ) ; numbers needed to treat for 4 years to avoid one event were 21 and 33 , respectively . All-cause mortality was reduced nonsignificantly by 22 % ( [ −49 to 18 ] , P = 0.245 ) and 37 % ( [ −64 to 9 ] , P = 0.98 ) , respectively . The overall safety profile of atorvastatin was similar between age-groups . CONCLUSIONS —Absolute and relative benefits of statin therapy in older patients with type 2 diabetes are substantial , and all patients warrant treatment unless specifically contraindicated Objective To quantify associations of chronic kidney disease stages with major cardiovascular disease and non-vascular mortality in the general adult population . Design Prospect i ve population based cohort study . Setting Reykjavik , Icel and . Participants 16 958 people aged 33 - 81 years without manifest vascular disease and with available information on stage of chronic kidney disease ( defined by both estimated glomerular filtration rate and urinary protein ) at study entry . Main outcome measures Hazard ratios for time to major coronary heart disease outcomes and mortality . Results 1210 ( 7 % ) of participants had chronic kidney disease at entry . During a median follow-up of 24 years , 4010 coronary heart disease outcomes , 559 deaths from stroke , and 3875 deaths from non-vascular causes were recorded . Compared with the reference group ( estimated glomerular filtration rate 75 - 89 ml/min/1.73 m2 and no proteinuria ) , people with lower renal function within the normal range of glomerular filtration rate did not have significantly higher risk of coronary heart disease . By contrast , in 1210 ( 7 % ) participants with chronic kidney disease at entry , hazard ratios for coronary heart disease , adjusted for several conventional cardiovascular risk factors , were 1.55 ( 95 % confidence interval 1.02 to 2.35 ) for stage 1 , 1.72 ( 1.30 to 2.24 ) for stage 2 , 1.39 ( 1.22 to 1.58 ) for stage 3a , 1.90 ( 1.22 to 2.96 ) for stage 3b , and 4.29 ( 1.78 to 10.32 ) for stage 4 . Information on chronic kidney disease increased discrimination and reclassification indices for coronary heart disease when added to conventional risk factors ( P<0.01 ) . The incremental gain provided by chronic kidney disease was lower than that provided by diabetes or smoking ( C index increases of 0.0015 , 0.0024 , and 0.0124 respectively ) . Hazard ratios with chronic kidney disease were 0.97 ( 0.82 to 1.15 ) for cancer mortality and 1.26 ( 1.07 to 1.50 ) for other non-vascular mortality . Conclusions In people without manifest vascular disease , even the earliest stages of chronic kidney disease are associated with excess risk of subsequent coronary heart disease . Assessment of chronic kidney disease in addition to conventional risk factors modestly improves prediction of risk for coronary heart disease in this population . Further studies are needed to investigate associations between chronic kidney disease and non-vascular mortality from causes other than cancer The West of Scotl and Coronary Prevention Study ( WOSCOPS ) showed that pravastatin reduced the risk of coronary heart disease ( CHD ) events in 6,595 middle-aged hypercholesterolaemic men aged 45 - 64 years without prior myocardial infa rct ion followed for an average of 4.9 years . We hypothesised prospect ively ( a ) that baseline levels of haemorheological variables were related to baseline and incident CHD and to mortality ; and ( b ) that reduction in lipoproteins by pravastatin would lower plasma and blood viscosity , a potential contributory mechanism to CHD events . We therefore studied plasma and blood viscosity , fibrinogen , haematocrit , and blood cell counts at baseline and 1 year . At baseline , plasma and blood viscosity were related to risk factors , CHD measures , and claudication . On univariate analysis , baseline levels of all rheological variables ( except platelet count ) were related to incident CHD ; CHD mortality ; and total mortality . On multivariate analysis including baseline CHD and risk factors , plasma and blood viscosity , haematocrit and white cell count each remained significantly associated with incident CHD ; while fibrinogen remained an independent predictor of mortality ( all p < 0.03 ) . After one year , lipoprotein reduction by pravastatin was associated with significant reductions ( about one quarter of a st and ard deviation ) in plasma viscosity ( mean difference 0.02 mPa.s , p < 0.001 ) and in blood viscosity ( mean difference 0.06 mPa.s , p<0.001 ) , but was not associated with significant changes in other rheological variables . We therefore suggest that pravastatin therapy , which reduces elevated lipoproteins in hypercholesterolaemic men , may lower risks of CHD and mortality partly by lowering plasma and blood viscosity . Further studies are required to test this hypothesis Abstract Objectives To determine whether data on proteinuria are useful for refining estimates of risk based on kidney function alone , and whether the results of kidney function tests can be a useful adjunct to data on proteinuria . Design Analysis of data from a r and omised trial . Impaired kidney function was defined as low glomerular filtration rate ( < 60 ml/min/1.73 m2 ) and proteinuria ( 1 + protein ) on dipstick urinalysis . Setting Study of cholesterol and recurrent events : a r and omised trial of pravastatin 40 mg daily versus placebo . Participants 4098 men and women with previous myocardial infa rct ion . Main outcome measures All cause mortality and cardiovascular events . Results 371 participants died in nearly 60 months of follow-up . Compared with participants without proteinuria or impaired kidney function , patients with both characteristics were at high risk ( hazard ratio 2.39 , 95 % confidence interval 1.72 to 3.30 ) , and those with only proteinuria or only impaired kidney function were at intermediate risk ( 1.69 , 1.32 to 2.16 ; 1.41 , 1.12 to 1.79 , respectively ) of dying from any cause . The results were similar for cardiovascular outcomes , including new cases of heart failure , stroke , and coronary death or non-fatal myocardial infa rct ion . A grade d increase in the risk of all cause mortality was seen for severity of renal impairment and degree of proteinuria by dipstick . Conclusions The presence or absence of proteinuria on dipstick urinalysis may be used to refine estimates of risk based on kidney function alone Children with hyperlipidemia secondary to renal disease develop premature atherosclerosis and glomerulosclerosis . The aims of this pilot study were to find the dosage and short-term efficacy of simvastatin and potential adverse events in children with chronic kidney diseases . This was a r and om , double-blind , placebo-controlled , cross-over clinical trial performed on children with hyperlipidemia secondary to kidney disorders . After being placed on a diet for 3 months , patients were r and omly placed in one of two balanced group blocks and treated with diet plus placebo or simvastatin at doses of 5 mg for children weighing 30 kg or less and 10 mg for children weighing over 30 kg , for 1 month , and then doubled for two more months . After this treatment , patients were placed on a diet for a 3-month washout period . During the last trial phase , patients previously treated with simvastatin were administered a placebo , and vice versa . A total of 25 patients with ages ranging from 4 years to 17 years were included in the study . A significant decrease in the levels of serum cholesterol ( 26.4 % ) , low-density lipoprotein ( LDL ) ( 35.4 % ) and triglycerides ( 23.1 % ) was noted during the study , primarily during the simvastatin treatments , in which case cholesterol , LDL and triglycerides decreased by 23.3 % , 33.7 % and 21 % , respectively . High-density lipoprotein ( HDL ) levels increased moderately ( 10.7 % ) during the study but without differences during simvastatin treatment . No differences were found across groups with respect to adverse events . In the short-term the combination of diet and simvastatin was effective in lowering hyperlipidemia in children with renal disorders Summary Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infa rct ion , ischaemic stroke , and the need for coronary revascularisation in people without kidney disease , but its effects in people with moderate-to-severe kidney disease are uncertain . The SHARP trial aim ed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients . Methods This r and omised double-blind trial included 9270 patients with chronic kidney disease ( 3023 on dialysis and 6247 not ) with no known history of myocardial infa rct ion or coronary revascularisation . Patients were r and omly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo . The key prespecified outcome was first major atherosclerotic event ( non-fatal myocardial infa rct ion or coronary death , non-haemorrhagic stroke , or any arterial revascularisation procedure ) . All analyses were by intention to treat . This trial is registered at Clinical Trials.gov , NCT00125593 , and IS RCT N54137607 . Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo . Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L ( SE 0·02 ; with about two-thirds compliance ) during a median follow-up of 4·9 years and produced a 17 % proportional reduction in major atherosclerotic events ( 526 [ 11·3 % ] simvastatin plus ezetimibe vs 619 [ 13·4 % ] placebo ; rate ratio [ RR ] 0·83 , 95 % CI 0·74–0·94 ; log-rank p=0·0021 ) . Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infa rct ion or died from coronary heart disease ( 213 [ 4·6 % ] vs 230 [ 5·0 % ] ; RR 0·92 , 95 % CI 0·76–1·11 ; p=0·37 ) and there were significant reductions in non-haemorrhagic stroke ( 131 [ 2·8 % ] vs 174 [ 3·8 % ] ; RR 0·75 , 95 % CI 0·60–0·94 ; p=0·01 ) and arterial revascularisation procedures ( 284 [ 6·1 % ] vs 352 [ 7·6 % ] ; RR 0·79 , 95 % CI 0·68–0·93 ; p=0·0036 ) . After weighting for subgroup-specific reductions in LDL cholesterol , there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined , and , in particular , they were similar in patients on dialysis and those who were not . The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination ( 9 [ 0·2 % ] vs 5 [ 0·1 % ] ) . There was no evidence of excess risks of hepatitis ( 21 [ 0·5 % ] vs 18 [ 0·4 % ] ) , gallstones ( 106 [ 2·3 % ] vs 106 [ 2·3 % ] ) , or cancer ( 438 [ 9·4 % ] vs 439 [ 9·5 % ] , p=0·89 ) and there was no significant excess of death from any non-vascular cause ( 668 [ 14·4 % ] vs 612 [ 13·2 % ] , p=0·13 ) . Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease . Funding Merck/Schering-Plough Pharmaceuticals ; Australian National Health and Medical Research Council ; British Heart Foundation ; UK Medical Research Council The MEGA study was a prospect i ve , r and omized , open-labeled , blinded-endpoints study conducted in Japan to evaluate the primary preventive effect of pravastatin against coronary heart disease ( CHD ) , in which 8214 subjects were r and omized to diet or diet plus pravastatin . The intention-to-treat ( ITT ) analysis showed that pravastatin reduced the incidence of CHD ( hazard ratio=0.67 ; 95 per cent confidence interval ( CI ) : 0.49 - 0.91 ) and of stroke events , which was the secondary endpoint in the MEGA study ( hazard ratio=0.83 ; 95 per cent CI : 0.57 - 1.21 ) . Owing to considerable treatment changes , it is also of interest to estimate the causal effect of treatment that would have been observed had all patients complied with the treatment to which they were assigned . In this paper , we present an intensity score method developed for clinical trials with time-to-event outcomes that correct for treatment changes during follow-up . The proposed method can be easily extended to the estimation of time-dependent treatment effects , where the technique of g-estimation has been difficult to apply in practice . We compared the performances of the proposed method with other methods ( as-treated , ITT , and g-estimation analysis ) through simulation studies , which showed that the intensity score estimator was unbiased and more efficient . Applying the proposed method to the MEGA study data , several prognostic factors were associated with the process of treatment changes , and after adjusting for these treatment changes , larger treatment effects for pravastatin were observed for both CHD and stroke events . The proposed method provides a valuable and flexible approach for estimating treatment effect adjusting for non-r and om non-compliance AIM To evaluate the contribution of the 46C > T polymorphism of the Factor XII ( FXII ) gene to risk for coronary heart disease ( CHD ) in the West of Scotl and Coronary Prevention Study ( WOSCOPS ) of men with high cholesterol . BACKGROUND WOSCOPS is a primary prevention trial that demonstrated the effectiveness of pravastatin in reducing morbidity and mortality from CHD . FXII is a protein of the contact system that plays a key role in both coagulation and fibrinolysis . Elevated activated FXII ( FXIIa ) levels have been previously associated with CHD . Plasma FXIIa levels are strongly determined by a 46C > T polymorphism in the FXII gene . RESULTS 441 CHD cases and 990 controls were genotyped . The frequency of TT homozygotes was 8.3 % in controls and 11.8 % in cases ( P=0.04 ) . When compared with the CC+CT group ( after adjustment for age , blood pressure , BMI , fibrinogen and lipid levels ) the TT genotype was an independent risk factor for CHD ( OR 1.48 95 % CI 1.01 - 2.17 ) , an effect that was only significant in the pravastatin group ( OR 1.95 95 % CI 1.09 - 3.47 ) and not in the placebo group ( OR 1.20 , 95%CI 0.72 - 2.02 ) . Compared with risk in the placebo group as a whole ( reference group ) , and after adjustment for other risk factors , men with the CC or CT genotype , but not the TT genotype showed a significant benefit from pravastatin treatment ( OR , respectively , 0.61 ( 0.46 - 0.81 ) and 0.56 ( 0.40 - 0.79 ) compared with 1.10 ( 0.64 - 1.96 ) . In a subgroup of these men , subjects with the TT genotype had , as expected , baseline levels of FXIIa that were 50 % lower than those with the CC genotype , with CT subjects having intermediate levels ( P<0.001 by Kruskal-Wallis test ) . CONCLUSIONS The TT genotype of the FXII 46C > T polymorphism is associated with a high risk of CHD in men with high cholesterol . We hypothesise that reduced fibrinolysis in these men , as a consequence of lower plasma FXIIa , may be the mechanism leading to higher risk , and that pravastatin treatment may enhance this effect Objective . There have been no endpoint studies with statins for patients with severe renal failure . The purpose of this prospect i ve , open , r and omized , controlled study was to investigate whether atorvastatin ( 10 mg/day ) would alter cardiovascular endpoints and the overall mortality rate of patients with chronic kidney disease stage 4 or 5 ( creatinine clearance < 30 ml/min ) . Material and methods . The study subjects comprised 143 patients who were r and omized either to placebo ( controls ; n=73 ; mean age 69.5 years ) or to treatment with atorvastatin ( n=70 ; mean age 67.9 years ) . The patients included were either non-dialysis ( n=33 ) , haemodialysis ( n=97 ) or peritoneal dialysis ( n=13 ) patients . Analysis focused on the primary endpoints of all-cause mortality , non-lethal acute myocardial infa rct ion , coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty . Statistical analysis for endpoint data was mainly by intention-to-treat . Results . Primary endpoints occurred in 74 % of the subjects . There was no difference in outcome between the control and atorvastatin groups . The 5-year endpoint-free survival rate from study entry was ≈20 % . Atorvastatin was withdrawn in ≈20 % of patients due to unacceptable side-effects . In the atorvastatin group , low-density lipoprotein ( LDL ) cholesterol was reduced by 35 % at 1 month and then sustained . The controls showed a progressive reduction in LDL cholesterol until 36 months . Conclusions . Although atorvastatin reduced total and LDL cholesterol effectively it was not beneficial regarding the long-term outcomes of cardiovascular endpoints or survival . In contrast to other patient groups , patients with severe chronic kidney disease , especially those on dialysis , seem to derive limited benefit from this lower dose of atorvastatin The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial ( ALLHAT ) provides a unique opportunity to compare the long-term relative safety and efficacy of angiotensin-converting enzyme inhibitor and calcium channel blocker – initiated therapy in older hypertensive individuals . Patients were r and omized to amlodipine ( n=9048 ) or lisinopril ( n=9054 ) . The primary outcome was combined fatal coronary heart disease or nonfatal myocardial infa rct ion , analyzed by intention-to-treat . Secondary outcomes included all-cause mortality , stroke , combined cardiovascular disease ( CVD ) , end-stage renal disease ( ESRD ) , cancer , and gastrointestinal bleeding . Mean follow-up was 4.9 years . Blood pressure control was similar in nonblacks , but not in blacks . No significant differences were found between treatment groups for the primary outcome , all-cause mortality , ESRD , or cancer . Stroke rates were higher on lisinopril in blacks ( RR=1.51 , 95 % CI 1.22 to 1.86 ) but not in nonblacks ( RR=1.07 , 95 % CI 0.89 to 1.28 ) , and in women ( RR=1.45 , 95 % CI 1.17 to 1.79 ) , but not in men ( RR=1.10 , 95 % CI 0.92 to 1.31 ) . Rates of combined CVD were higher ( RR=1.06 , 95 % CI 1.00 to 1.12 ) because of higher rates for strokes , peripheral arterial disease , and angina , which were partly offset by lower rates for heart failure ( RR=0.87 , 95 % CI 0.78 to 0.96 ) on lisinopril compared with amlodipine . Gastrointestinal bleeds and angioedema were higher on lisinopril . Patients with and without baseline coronary heart disease showed similar outcome patterns . We conclude that in hypertensive patients , the risks for coronary events are similar , but for stroke , combined CVD , gastrointestinal bleeding , and angioedema are higher and for heart failure are lower for lisinopril-based compared with amlodipine-based therapy . Some , but not all , of these differences may be explained by less effective blood pressure control in the lisinopril arm Background — Patients with low HDL cholesterol ( HDL-C ) and elevated triglyceride had an increased risk for coronary heart disease ( CHD ) events and received the greatest benefit with fibrate therapy in sub study analyses of the Helsinki Heart Study and the Bezafibrate Infa rct ion Prevention Study . Methods and Results —In this post hoc analysis of the Sc and inavian Simvastatin Survival Study , which enrolled patients with elevated LDL cholesterol ( LDL-C ) and CHD , subgroups defined by HDL-C and triglyceride quartiles were compared to examine the influence of HDL-C and triglyceride on CHD events and response to therapy . Patients in the lowest HDL-C ( < 1.00 mmol/L [ 39 mg/dL ] ) and highest triglyceride ( > 1.80 mmol/L [ 159 mg/dL ] ) quartiles ( lipid triad ; n=458 ) had increased proportions of other features of the metabolic syndrome ( increased body mass index , hypertension , diabetes ) , men , prior myocardial infa rct ion , prior revascularization , and & bgr;-blocker use than patients in the highest HDL-C ( > 1.34 mmol/L [ 52 mg/dL ] ) and lowest triglyceride ( < 1.11 mmol/L [ 98 mg/dL ] ) quartiles ( isolated LDL-C elevation ; n=545 ) . The major coronary event rate was highest in lipid triad patients on placebo ( 35.9 % ) , and this subgroup had the greatest event reduction ( relative risk 0.48 , 95 % CI 0.33 to 0.69 ) ; a significant treatment-by-subgroup interaction ( P = 0.03 ) indicated a greater treatment effect in the lipid triad subgroup than the isolated LDL-C elevation subgroup . Conclusions — Patients with elevated LDL-C , low HDL-C , and elevated triglycerides were more likely than patients with isolated LDL-C elevation to have other characteristics of the metabolic syndrome , had increased risk for CHD events on placebo , and received greater benefit with simvastatin therapy Urinary albumin excretion is a predictor for cardiovascular mortality and morbidity . We investigated which parameters determine baseline urinary albumin excretion in nondiabetic subjects , without renal disease . In addition , we evaluated the parameters that predict the albuminuria-lowering efficacy of an angiotensin-converting enzyme inhibitor . In this sub study of the Prevention of Renal and Vascular Endstage Disease Intervention Trial , 384 microalbuminuric patients were included . Patient and biochemical characteristics were obtained at baseline and after 3 months of double-blinded , r and omized treatment ( fosinopril 20 mg or placebo ) . Mean age was 51.1±11.5 years , and 65.6 % were male . Median urinary albumin excretion was 22.2 mg per 24 hours . At baseline , mean arterial pressure ( & bgr;st and ardized=0.161 ; P=0.006 ) , urinary sodium excretion ( & bgr;st and ardized=0.154 ; P=0.011 ) , and estimated renal function were independently associated with albumin excretion . In these predominantly normotensive to prehypertensive subjects , fosinopril reduced albumin excretion by 18.5 % versus a 6.1 % increase on placebo after 3 months ( P<0.001 ) . Fosinopril use and blood pressure reduction independently predicted the change in urinary albumin excretion . Baseline urinary albumin excretion independently predicted the antialbuminuric effect of fosinopril ( & bgr;st and ardized=−0.303 ; P<0.001 ) . In conclusion , at baseline , sodium intake and blood pressure were positively associated with urinary albumin excretion . Fosinopril reduced albuminuria more than might be expected from its blood pressure – lowering effect alone , and this effect was more outspoken in subjects with higher baseline albumin excretion . Based on our data , we hypothesize that angiotensin-converting enzyme inhibition may result in superior cardiovascular protection when compared with other blood pressure – lowering agents in subjects with higher baseline levels of albuminuria Objective . To investigate the efficacy and safety of a daily dose of 10 mg of atorvastatin in patients with chronic kidney disease ( CKD ) stages 4 and 5 and a glomerular filtration rate of < 30 ml/min . Material and methods . This was an open , prospect i ve , r and omized study . A total of 143 patients were included : 73 were controls and 70 were prescribed 10 mg/day of atorvastatin . As efficacy variables , total cholesterol , low-density lipoprotein ( LDL ) cholesterol , high-density lipoprotein ( HDL ) cholesterol and triglyceride levels were determined at the start of the study and at 1 , 3 , 6 , 12 , 18 , 24 , 30 and 36 months . Results . The follow-up period was a mean of 20±14.4 months ( range 1–36 months ) for those on atorvastatin versus 22±12.7 months ( range 0.5–36 months ) for the controls . Compared with baseline values , patients treated with atorvastatin had significantly lower concentrations of total cholesterol at Month 36 ( 5.8 vs 4.4 mmol/l ; −23 % ; p<0.001 ) , of LDL cholesterol at Month 36 ( 3.6 vs 2.2 mmol/l ; −35 % ; p<0.001 ) and of triglycerides at Months 24 ( 2.5 vs 1.9 mmol/l ) and 36 ( 2.5 vs 1.8 mmol/l ) . The controls had significantly reduced levels of total cholesterol at Month 36 ( p<0.21 ) and of LDL cholesterol at Months 30 and 36 . Compared with the controls , the atorvastatin group had lower levels of total cholesterol and LDL cholesterol at Months 1–30 . Fifteen patients ( 21 % ) stopped taking their medication as they could not tolerate the side-effects , the most frequent complaints being gastrointestinal discomfort and headache . Conclusion . Although the medication caused no severe adverse events , we recommend caution when using atorvastatin for severe CKD patients until further evidence of its safety and efficacy is verified BACKGROUND AND OBJECTIVES Data suggest that atorvastatin may be nephroprotective . This sub analysis of the Treating to New Targets study investigated how intensive lipid lowering with 80 mg of atorvastatin affects renal function when compared with 10 mg in patients with coronary heart disease . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS A total of 10,001 patients with coronary heart disease and LDL cholesterol levels of < 130 mg/dl were r and omly assigned to double-blind therapy with 10 or 80 mg/d atorvastatin . Estimated GFR using the Modification of Diet in Renal Disease equation was compared at baseline and at the end of follow-up in 9656 participants with complete renal data . RESULTS Mean estimated GFR at baseline was 65.6 + /- 11.4 ml/min per 1.73 m2 in the 10-mg group and 65.0 + /- 11.2 ml/min per 1.73 m2 in the 80-mg group . At the end of follow-up ( median time to final creatinine measurement 59.5 months ) , mean change in estimated GFR showed an increase of 3.5 + /- 0.14 ml/min per 1.73 m2 with 10 mg and 5.2 + /- 0.14 ml/min per 1.73 m2 with 80 mg ( P < 0.0001 for treatment difference ) . In the 80-mg arm , estimated GFR improved to > or = 60 ml/min per 1.73 m2 in significantly more patients and declined to < 60 ml/min per 1.73 m2 in significantly fewer patients than in the 10-mg arm . CONCLUSIONS The expected 5-yr decline in renal function was not observed . Estimated GFR improved in both treatment groups but was significantly greater with 80 mg than with 10 mg , suggesting this benefit may be dosage related BACKGROUND There is evidence that dyslipidemia is associated with chronic kidney disease ( CKD ) and it has been implicated in the progression of renal damage . Optimal management of dyslipidemia should therefore lead to renal benefits . A number of experimental models demonstrate a beneficial effect of statins in ameliorating renal damage . However , the exact mechanism by which statins protect against renal damage remains unclear . METHODS In a placebo-controlled , r and omized , cross-over study we evaluated the influence of atorvastatin ( ATO ) 40 mg/day added to the renin-angiotensin-aldosterone systeme ( RAAS ) blockade on proteinuria and surrogate biomarkers of tubular damage or injury in 14 non-diabetic patients with proteinuria ( 0.4 - 1.8 g per 24 h ) with normal or declined kidney function ( eGFR 55 - 153 ml/min ) . In the eight-week run-in period , therapy using angiotensin converting enzyme inhibitors ( ACEI ) and /or angiotensin II subtype 1 receptor antagonists ( ARB ) was adjusted to achieve a blood pressure below 130/80 mm Hg . Next , patients were r and omly assigned to one of two treatment sequences : ATO/washout/placebo or placebo/washout/ATO . Clinical evaluation and laboratory tests were performed at the r and omization point and after each period of the study . The primary end point of this study was a change in proteinuria measured as 24-h urine protein excretion ( DPE ) . Secondary end points included urine N-acetyl-β-D-glucosaminidase ( NAG ) and α1-microglobulin ( α1 m ) excretion . RESULTS The ATO therapy significantly reduced urine excretion of α₁m ( p=0.033 ) and NAG ( p=0.038 ) as compared to placebo . There were no differences in proteinuria , blood pressure , eGFR and serum creatinine between the ATO and placebo groups . CONCLUSION Atorvastatin treatment is safe and improves biomarkers of tubular damage or injury in non-diabetic patients with CKD BACKGROUND The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome . No study , however , has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease ( CHD ) in hypertensive patients who are not conventionally deemed dyslipidaemic . METHODS Of 19342 hypertensive patients ( aged 40 - 79 years with at least three other cardiovascular risk factors ) r and omised to one of two antihypertensive regimens in the Anglo-Sc and inavian Cardiac Outcomes Trial , 10305 with non-fasting total cholesterol concentrations 6.5 mmol/L or less were r and omly assigned additional atorvastatin 10 mg or placebo . These patients formed the lipid-lowering arm of the study . We planned follow-up for an average of 5 years , the primary endpoint being non-fatal myocardial infa rct ion and fatal CHD . Data were analysed by intention to treat . FINDINGS Treatment was stopped after a median follow-up of 3.3 years . By that time , 100 primary events had occurred in the atorvastatin group compared with 154 events in the placebo group ( hazard ratio 0.64 [ 95 % CI 0.50 - 0.83 ] , p=0.0005 ) . This benefit emerged in the first year of follow-up . There was no significant heterogeneity among prespecified subgroups . Fatal and non-fatal stroke ( 89 atorvastatin vs 121 placebo , 0.73 [ 0.56 - 0.96 ] , p=0.024 ) , total cardiovascular events ( 389 vs 486 , 0.79 [ 0.69 - 0.90 ] , p=0.0005 ) , and total coronary events ( 178 vs 247 , 0.71 [ 0.59 - 0.86 ] , p=0.0005 ) were also significantly lowered . There were 185 deaths in the atorvastatin group and 212 in the placebo group ( 0.87 [ 0.71 - 1.06 ] , p=0.16 ) . Atorvastatin lowered total serum cholesterol by about 1.3 mmol/L compared with placebo at 12 months , and by 1.1 mmol/L after 3 years of follow-up . INTERPRETATION The reductions in major cardiovascular events with atorvastatin are large , given the short follow-up time . These findings may have implication s for future lipid-lowering guidelines OBJECTIVE We sought to assess the effects on cerebrovascular events of treating patients with stable coronary disease with low-density lipoprotein cholesterol ( LDL-C ) levels substantially below 100 mg/dl . BACKGROUND Lowering LDL-C with statins has been shown to reduce the risk of stroke in patients with stable coronary disease . In observational studies , naturally low cholesterol levels have been associated with an increased risk of hemorrhagic stroke . The cerebrovascular benefits of treating patients with stable coronary disease to LDL-C levels substantially below 100 mg/dl have not been previously investigated . METHODS We describe an analysis of cerebrovascular events in the Treating to New Targets study , a trial where 10,001 patients with documented coronary disease were r and omized to treatment with atorvastatin at 10 mg/day or 80 mg/day and followed for a median of 4.9 years . RESULTS Mean LDL-C levels were 101 mg/dl on 10 mg atorvastatin and 77 mg/dl on 80 mg . In addition to the reduction in major cardiovascular events ( hazard ratio 0.78 , 95 % confidence interval [ CI ] 0.69 to 0.89 ; p = 0.0002 ) , the primary end point of the trial , patients in the 80-mg arm experienced a reduction in cerebrovascular events ( hazard ratio 0.77 , 95 % CI 0.64 to 0.93 ; p = 0.007 ) and stroke ( hazard ratio 0.75 , 95 % CI 0.59 to 0.96 ; p = 0.02 ) . Each 1-mg/dl reduction in LDL-C with treatment was associated with a 0.6 % relative risk reduction in cerebrovascular events ( p = 0.002 ) and a 0.5 % relative risk reduction in stroke ( p = 0.041 ) . The incidence of hemorrhagic stroke was similar in the 80-mg and 10-mg groups , 16 and 18 respectively , and the hemorrhagic strokes were distributed evenly across quintiles of achieved LDL-C during treatment . CONCLUSIONS Among patients with established coronary disease , treating to an LDL-cholesterol substantially below 100 mg/dl with 80 mg/day atorvastatin reduces both stroke and cerebrovascular events by an additional 20 % to 25 % compared with the 10 mg/day dose . An increase in hemorrhagic stroke was not seen at low LDL-C levels . ( Treating to New Targets ; http://www . clinical trials.gov ; NCT00327691 ) OBJECTIVES In Incremental Decrease in Endpoints through Aggressive Lipid-lowering ( IDEAL ) , we compared cardiovascular outcomes in patients with and without chronic kidney disease ( CKD ) ( estimated glomerular filtration rate < 60 mL min(-1 ) 1.73 m(-2 ) ) and analysed relationships between lipoprotein components ( LC ) and major coronary events ( MCE ) and other cardiovascular ( CV ) events . DESIGN Exploratory analysis of CV endpoints in a r and omized trial comparing high dose of atorvastatin to usual dose of simvastatin on MCE . SETTING S Patients with CKD were compared with the non-CKD patients . Cox regression models were used to study the relationships between on-treatment levels of LC and incident MCE . FINDINGS Chronic kidney disease was strongly associated with cardiovascular end-points including total mortality . In patients with CKD , a significant benefit of high dose atorvastatin treatment was found for any CV events , stroke and peripheral artery disease , but not for MCE . However , all cardiovascular end-points except stroke and CV mortality were reduced in the non-CKD group . Differential changes in LC or relationships to LC could not explain the different treatment outcomes in MCE in the two groups . INTERPRETATION Chronic kidney disease was a powerful risk factor for all cardiovascular end-points . The reason why the significant reductions achieved by high-dose statin treatment in most CV end-points in the non-CKD group were only in part matched by similar reductions in the CKD patients is not apparent . This difference did not result from differential changes in or relations to LC , but limited power may have increased the possibility of chance findings BACKGROUND This post hoc analysis of the Aggressive Lipid-Lowering Initiation Abates New Cardiac Events ( ALLIANCE ) Study investigates the effect of focused atorvastatin therapy versus usual care on cardiovascular outcomes in patients with coronary heart disease ( CHD ) with and without chronic kidney disease ( CKD ) . STUDY DESIGN Prospect i ve r and omized open-label ; median follow-up , 54.3 months . SETTING & PARTICIPANTS Managed care or Veterans Affairs facilities ; 2,442 patients with CHD with dyslipidemia ; mean age , 61.6 years . INTERVENTION Focused atorvastatin therapy to a low-density lipoprotein cholesterol goal of less than 80 mg/dL or maximum dose of 80 mg/d versus usual care as deemed appropriate by patients ' regular physicians . PREDICTOR Baseline estimated glomerular filtration rate ( eGFR ) calculated using the Modification of Diet in Renal Disease Study equation of less than 60 mL/min/1.73 m(2 ) ( patients with CKD ) and 60 mL/min/1.73 m(2 ) or greater ( patients without CKD ) . OUTCOMES & MEASUREMENTS The primary end point was time to first cardiovascular event . Change from baseline eGFR was assessed in 1,768 patients with follow-up renal data . RESULTS At baseline , 579 patients ( 23.7 % ) had CKD : 31.6 % of these patients experienced a primary cardiovascular event during the study versus 23.6 % of patients without CKD ( hazard ratio [ HR ] , 1.41 ; 95 % confidence interval [ CI ] , 1.18 to 1.68 ; P < 0.001 ) . Compared with usual care , atorvastatin therapy reduced the relative risk of a primary outcome by 28 % in patients with CKD ( HR , 0.72 ; 95 % CI , 0.54 to 0.97 ; P = 0.02 ) and 11 % in patients without CKD ( HR , 0.89 ; 95 % CI , 0.74 to 1.07 ; P = 0.3 ) ( P for treatment by CKD interaction = 0.2 ) . There was no decrease in eGFR in atorvastatin-treated patients during the course of the study . LIMITATIONS Follow-up of atorvastatin patients was restricted to every 6 months ; interim data were unavailable for usual-care patients . CONCLUSIONS Patients with CHD and CKD are at increased risk of cardiovascular events . Compared with usual care , focused atorvastatin treatment decreased cardiovascular risk for established patients in real-world setting s , with no significant difference in treatment effects observed between patients with and without CKD Background The MEGA study is a r and omized controlled trial conducted in Japan to evaluate the primary preventive effect of pravastatin against coronary heart disease ( CHD ) , in which 8214 subjects are r and omized to diet or diet plus pravastatin . Pravastatin reduces the incidence of CHD ( hazard ratio = 0.67 ; 95%CI : 0.49—0.91 ) . In the MEGA study , in addition to the usual loss to follow-up cases , there is another problem of drop-outs due to the refusal of further follow-up at 5 years . Purpose To estimate the treatment effect adjusting for some types of dependent censorings observed in the MEGA study and to assess the sensitivity of st and ard analysis results for these censoring cases . Methods The proposed method is a straightforward extension of the inverse probability of censoring weighted ( IPCW ) method for setting s with more than one reason for censoring , where the propensities for drop-outs are modeled separately for each reason . Simulation studies are also conducted to compare the properties of the IPCW estimate with the st and ard analysis assuming independent censorings . Results Simulation studies show that the IPCW estimate can correct for selection bias due to dependent censoring that can be explained by measured factors , while the st and ard analysis is biased . Applying the proposed method to the MEGA study data , several prognostic factors are associated with the censoring processes , and after adjusting for these dependent censorings , slightly larger treatment effects for pravastatin are observed for both CHD ( primary endpoint ) and stroke ( secondary endpoint ) events . Limitations The method developed is based on the fundamental assumption of sequentially ignorable censoring . Conclusions Our proposed method provides a valuable approach for estimating treatment effect adjusting for several types of dependent censorings . Dependent censorings observed in the MEGA study did not cause a severe selection bias attributable to the covariates and the results from the st and ard analysis were robust in relation to the censorings . Clinical Trials 2007 ; 4 : 318—328 . http:// Background — It is well known that statins reduce the risk of cardiovascular disease . However , the effect of statins in women for the primary prevention of cardiovascular disease has not been determined . We conducted an exploratory analysis of the effect of diet plus pravastatin therapy on the primary prevention of cardiovascular events in women with data from a large-scale primary prevention trial with pravastatin . Methods and Results — Patients with hypercholesterolemia ( 5.7 to 7.0 mmol/L ) and no history of coronary heart disease or stroke were r and omized to diet or diet plus pravastatin 10 to 20 mg/d and followed up for ≥5 years . We investigated the effect of diet plus pravastatin treatment on cardiovascular events in 5356 women during the 5-year follow-up . The incidence of cardiovascular events in the women was 2 to 3 times lower than that in men . The occurrence of cardiovascular events was 26 % to 37 % lower in the diet plus pravastatin treatment group than in the diet alone group . Although these differences did not reach statistical significance , the overall risk reductions were similar to those in men . Notably , women ≥60 years of age treated with diet plus pravastatin had markedly higher risk reductions for coronary heart disease ( 45 % ) , coronary heart disease plus cerebral infa rct ion ( 50 % ) , and stroke ( 64 % ) than did women treated with diet alone . Conclusions — Treatment with pravastatin in women with elevated cholesterol but no history of cardiovascular disease provides a benefit similar to that seen in men , and this benefit is more marked in older women . This treatment should be considered routinely for primary cardiovascular protection in women with elevated cholesterol levels Context Long-term outcomes of patients with a reduced glomerular filtration rate ( GFR ) who are treated for hypertension are not well-known . Contribution This analysis of a large multicenter trial found that coronary heart disease ( CHD ) was much more common than end-stage renal disease ( 15 % vs. 6 % ) in hypertensive patients with moderate to severe reductions in GFR who were followed for 6 years . Lower baseline GFR was associated with higher risk for CHD independent of other risk factors . Neither amlodipine nor lisinopril is superior to chlorthalidone in preventing CHD , stroke , or combined CVD , and chlorthalidone is superior to both for preventing heart failure , independent of level of renal function . Caution s These are post hoc subgroup findings , and proteinuria was not measured . The Editors It is estimated that more than 10 million Americans have chronic kidney disease ( 1 , 2 ) . The prevalence of chronic kidney disease is particularly high in older adults ; it is estimated to be greater than 25 % in persons older than 70 years of age . Patients with chronic kidney disease are at very high risk for cardiovascular disease ( CVD ) ( 3 - 8 ) . However , the long-term outcomes of older patients who have a mild or moderate reduction in glomerular filtration rate ( GFR ) , particularly with regard to CVD , are not well-known . Because of the large population of older adults with chronic kidney disease , it is important , from a public health and a clinical st and point , to quantify and underst and the comparative risks for CVD and renal disease in these patients . Management of hypertension is an important aspect of management in patients with chronic kidney disease ; in patients with proteinuria , drugs that inhibit the reninangiotensin axis have been shown to be superior to conventional antihypertensive drug therapy for preservation of renal function ( 1 , 9 , 10 ) . However , it is uncertain whether the choice of antihypertensive drug therapy affects risk for CVD in patients with chronic kidney disease ( 11 , 12 ) . The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) is a large clinical trial design ed to compare the efficacy of treatment with different first-line antihypertensive agents on CVD outcomes in high-risk patients with hypertension who are older than 55 years of age ( 13 - 15 ) . The objectives of this report from the ALLHAT data are to 1 ) compare rates of cardiovascular events with rates of development of end-stage renal disease ( ESRD ) in high-risk older adults with hypertension who have reduced GFR ; 2 ) determine whether reduced GFR is independently associated with an increased risk for CVD after adjusting for traditional cardiovascular risk factors ; and 3 ) report the efficacy of first-step treatment with a calcium-channel blocker ( amlodipine ) or an angiotensin-converting enzyme ( ACE ) inhibitor ( lisinopril ) , each compared with a diuretic ( chlorthalidone ) , in modifying CVD outcomes in high-risk patients with hypertension who are stratified by baseline GFR . Methods The rationale and design of ALLHAT have been presented in detail elsewhere ( 13 ) . The study received institutional review board approval , and participants provided written informed consent . Participants were men and women 55 years of age or older who had hypertension with at least 1 additional risk factor for coronary heart disease ( CHD ) . The risk factors included previous ( > 6 months ) myocardial infa rct ion ( MI ) or stroke , left ventricular hypertrophy demonstrated by electrocardiography or echocardiography , history of type 2 diabetes , current cigarette smoking , high-density lipoprotein cholesterol level of less than 0.91 mmol/L ( < 35 mg/dL ) , and documentation of other atherosclerotic CVD . Exclusion criteria included a history of symptomatic heart failure and /or a known left ventricular ejection fraction of less than 0.35 and a serum creatinine level greater than 176.8 mol/L ( > 2 mg/dL ) as reported by the investigator . Participants ( n= 33 357 ) were recruited at 623 centers in the United States , Canada , Puerto Rico , and the U.S. Virgin Isl and s between February 1994 and January 1998 ( Appendix Figure 1 ) . Appendix Figure 1 . R and omization and follow-up of participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) by treatment group . Block r and omization was stratified by center . Participants were r and omly assigned in a double-blind manner and in a 1.7:1:1 ratio to chlorthalidone , amlodipine , or lisinopril . A fourth arm of the study using the -blocker doxazosin was stopped early and is not considered in this report ( 16 ) . The goal blood pressure in each r and omly assigned group was less than 140/90 mm Hg , to be achieved by titrating the assigned study drug ( step 1 ) and by adding study -supplied , open-label agents ( atenolol , clonidine , or reserpine [ step 2 ] or hydralazine [ step 3 ] ) when necessary , at the physician 's discretion ( 16 , 17 ) . Nonpharmacologic lifestyle approaches to treatment of hypertension were recommended according to national guidelines . Other drugs , including low doses of open-label step 1 drug classes , were permitted if clinical ly indicated . Follow-up visits were at 1 month ; 3 , 6 , 9 , and 12 months ; and every 4 months thereafter . Levels of serum creatinine were measured in a single central laboratory using VITROS ( Ortho Clinical Diagnostics , Rochester , New York ) , which had a coefficient of variation of approximately 2 % . Creatinine measurements were calibrated to the Modification of Diet in Renal Disease ( MDRD ) laboratory , and no additional correction was found to be necessary ( 18 ) . A total of 1460 participants ( 4.4 % ) were missing creatinine values , and thus estimated GFR , at baseline . The simplified MDRD Study equation was used to estimate GFR ( mL/min per 1.73 m2 ) according to the following formula : 186.3 ( serum creatinine in mg/dL 1.154 ) ( age in years 0.203 ) 1.212 ( if black ) 0.742 ( if female ) ( 19 ) . Patients were classified into 3 baseline categories of GFR consistent with recommendations in the National Kidney Foundation Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines on Chronic Kidney Disease : normal or increased ( 90 mL/min per 1.73 m2 ) , mild reduction ( 60 to 89 mL/min per 1.73 m2 ) , and moderate or severe reduction ( < 60 mL/min per 1.73 m2 ) ( 1 ) . Because a serum creatinine level of greater than 176.8 mol/L ( > 2 mg/dL ) was an exclusion criterion , the percentage of patients with severe chronic kidney disease ( estimated GFR 29 mL/min per 1.73 m2 ) at baseline was very small ( 0.6 % ) . Therefore , as in another study ( 6 ) , these participants were considered along with those with moderate chronic kidney disease ( GFR 30 to 59 mL/min per 1.73 m2 ) . Patients were also classified as diabetic or not diabetic by baseline history of diabetes . The primary outcome was fatal CHD or nonfatal MI . Combined CVD was defined as a composite of the primary outcome , coronary revascularization , hospitalized angina , stroke , other treated angina , heart failure ( fatal , hospitalized , or treated nonhospitalized ) , and peripheral arterial disease . Coronary revascularization included coronary artery bypass grafting , percutaneous angioplasty , insertion of stents , and atherectomy . Peripheral vascular disease included intermittent claudication or arterial disease of the lower extremities leading to procedures , such as revascularizations , angioplasty of peripheral arteries , or amputation . End-stage renal disease included death from kidney disease , kidney transplantation , and start of long-term kidney dialysis . Study outcomes were defined in the ALLHAT Manual of Operations ( available from the authors on request ) , were assessed by site investigators at follow-up visits , and were reported to the Clinical Trials Center . Medical review ers from the Clinical Trials Center review ed all events for concordance with study criteria . More detailed information was collected on a r and om ( 10 % ) subset of CHD and stroke events and was review ed by the Endpoints Subcommittee to vali date the procedure of using physician diagnoses . Statistical Analyses Data were analyzed according to the participants ' r and omly assigned treatments regardless of their subsequent medications ( intention-to-treat analysis ) . Baseline characteristics were compared across treatments and the 3 GFR groups by using the Z-test for continuous covariates and contingency table analyses for categorical data . Cox proportional hazards models were used to obtain hazard ratios and 95 % CIs for time to CHD , combined CVD , and stroke to assess the effects of treatment within each of the 3 GFR strata . Because baseline characteristics are similar across treatment groups , no adjustment was deemed necessary . Additional models were used to assess the impact of baseline GFR ( using deciles ) on CHD and combined CVD . Baseline characteristics are not expected to be similar across the various GFR groups defined by deciles ; therefore , adjustments are necessary . Cox test assumptions were examined using loglog plots and tests of treatment by time ( time-dependent ) interaction terms . Because the assumptions were violated in the case of heart failure , logistic models were used to estimate odds ratios for this end point . The consistency of treatment effects across subgroups was examined in the Cox and logistic models by calculating the differences in the log likelihood for models with and without the interaction terms . Treatment effects by GFR subgroup were also analyzed for participants with a history of diabetes by using the aforementioned methods . A P value less than 0.05 indicated statistical significance for the results . Role of the Funding Sources This study was supported by contract NO1-HC-35130 from the National Heart , Lung , and Blood Institute ( NHLBI ) ; the NHLBI was involved in the collection , analysis , and interpretation of the data and the decision to su bmi t the manuscript for publication but was not involved in the direct operations of the study centers . Study medications were supplied by Abstract Objectives : To investigate whether baseline serum cholestanol : cholesterol ratio , which is negatively related to cholesterol synthesis , could predict reduction of coronary events in the Sc and inavian simvastatin survival study . Design : Follow up of patients with coronary heart disease in whom baseline ratios were related to major coronary events . Setting : Four universities in Finl and . Subjects : A subgroup of 868 patients with coronary heart disease selected from the Sc and inavian simvastatin survival study . Intervention : Treatment with simvastatin or placebo . Main outcome measures : Serum concentrations of low density lipoprotein and high density lipoprotein cholesterol , total triglyceride concentration , and cholesterol : cholestanol ratio . Major coronary events . Results : With increasing baseline quarter of cholestanol distribution the reduction in relative risk increased gradually from 0.623 ( 95 % confidence interval 0.395 to 0.982 ) to 1.166 ( 0.791 to 1.72 ) . The risk of recurrence of major coronary events increased 2.2-fold ( P<0.01 ) by multiple logistic regression analysis between the lowest and highest quarter of cholestanol . The ratio of cholestanol was related inversely to the body mass index and directly to high density lipoprotein cholesterol and triglyceride concentrations but their quarters of distribution were not related to risk reduction . Conclusions : Measurement of serum cholestanol concentration revealed a subgroup of patients with coronary heart disease in whom coronary events were not reduced by simvastatin treatment . Thus , patients with high baseline synthesis of cholesterol seem to be responders whereas those with low synthesis of cholesterol are non-responders Background There is evidence that dyslipidemia is associated with chronic kidney disease ( CKD ) . Experimental studies have established that lipids are damaging to the kidney and animal intervention studies show statins attenuate this damage . Small clinical trials , meta-analyses , observational studies and post-hoc analyses of cardiovascular intervention studies all support the concept that statins can reduce kidney damage in humans . Based on this background , a double blind r and omized placebo controlled trial was design ed to assess the effectiveness of atorvastatin 10 mg on slowing the progression of kidney disease in a population of patients with CKD . Method / Design The Lipid lowering and Onset of Renal Disease ( LORD ) trial is a three-year , single center , multi-site , double blind , r and omized , placebo controlled trial . The primary outcome measure is kidney function measured by eGFR calculated by both Modification of Diet in Renal Disease ( MDRD ) and Cockcroft and Gault equations . Secondary outcome measures include kidney function measured by 24-hour urine creatinine clearance and also 24-hour urinary protein excretion , markers of oxidative stress , inflammation and drug safety and tolerability . Discussion The results of this study will help determine the effectiveness and safety of atorvastatin and establish its effects on oxidative stress and inflammation in patients with CKD.Trial Registration BACKGROUND Intensified multifactorial intervention - with tight glucose regulation and the use of renin-angiotensin system blockers , aspirin , and lipid-lowering agents - has been shown to reduce the risk of nonfatal cardiovascular disease among patients with type 2 diabetes mellitus and microalbuminuria . We evaluated whether this approach would have an effect on the rates of death from any cause and from cardiovascular causes . METHODS In the Steno-2 Study , we r and omly assigned 160 patients with type 2 diabetes and persistent microalbuminuria to receive either intensive therapy or conventional therapy ; the mean treatment period was 7.8 years . Patients were subsequently followed observationally for a mean of 5.5 years , until December 31 , 2006 . The primary end point at 13.3 years of follow-up was the time to death from any cause . RESULTS Twenty-four patients in the intensive-therapy group died , as compared with 40 in the conventional-therapy group ( hazard ratio , 0.54 ; 95 % confidence interval [ CI ] , 0.32 to 0.89 ; P=0.02 ) . Intensive therapy was associated with a lower risk of death from cardiovascular causes ( hazard ratio , 0.43 ; 95 % CI , 0.19 to 0.94 ; P=0.04 ) and of cardiovascular events ( hazard ratio , 0.41 ; 95 % CI , 0.25 to 0.67 ; P<0.001 ) . One patient in the intensive-therapy group had progression to end-stage renal disease , as compared with six patients in the conventional-therapy group ( P=0.04 ) . Fewer patients in the intensive-therapy group required retinal photocoagulation ( relative risk , 0.45 ; 95 % CI , 0.23 to 0.86 ; P=0.02 ) . Few major side effects were reported . CONCLUSIONS In at-risk patients with type 2 diabetes , intensive intervention with multiple drug combinations and behavior modification had sustained beneficial effects with respect to vascular complications and on rates of death from any cause and from cardiovascular causes . ( Clinical Trials.gov number , NCT00320008 . Summary The effect of simvastatin ( 10–20 mg/day ) on kidney function , urinary albumin excretion rate and insulin sensitivity was evaluated in 18 Type 2 ( non-insulin-dependent ) diabetic patients with microalbuminuria and moderate hypercholesterolaemia ( total cholesterol ≥5.5 mmol·l−1 ) . In a double-blind , r and omized and placebo-controlled design treatment with simvastatin ( n=8 ) for 36 weeks significantly reduced total cholesterol ( 6.7±0.3 vs 5.1 mmol·l−1 ( p<0.01 ) ) , LDL-cholesterol ( 4.4±0.3 vs 2.9±0.2 mmol·l−1 ( p<0.001 ) ) and apolipoprotein B ( 1.05±0.04 vs 0.77±0.02 mmol·l−1 ( p<0.01 ) ) levels as compared to placebo ( n=10 ) . Both glomerular filtration rate ( mean±SEM ) ( simvastatin : 96.6±8.0 vs 96.0±5.7 ml·min−1·1.73 m−2 , placebo : 97.1±6.7 vs 88.8±6.0 ml·min−1·1.73 m−2 ) ( NS ) and urinary albumin excretion rate ( geometric mean x/÷ antilog SEM ) ( simvastatin : 18.4x/÷1.3vs 16.2 x/÷1.2 μg·min−1 , placebo 33.1 x/÷ 1.3 vs 42.7 x/÷ 1.3 μg·min−1)(NS ) were unchanged during the study . A euglycaemic hyperinsulinaemic clamp was performed at baseline and after 18 weeks in seven simvastatin- and nine placebo-treated patients . Isotopically determined basal and insulin-stimulated glucose disposal was similarly reduced before and during therapy in both the simvastatin ( 2.0±0.1 vs 1.9±0.1 ( NS ) and 3.1±0.6 vs 3.1±0.7 mg·kg−1·min−1 ( NS ) ) and the placebo group ( 1.9±0.1 vs 1.8±0.1 ( NS ) and 4.1±0.6 vs 3.8±0.2 mg·kg−1·min−1 ( NS ) ) . No different was observed in glucose storage or glucose and lipid oxidation before and after treatment . Further , the suppression of hepatic glucose production during hyperinsulinaemia was not influenced by simvastatin ( −0.7±0.8 vs −0.7±0.5 mg·kg−1·min−1 ( NS ) ) . In conclusion , despite marked improvement in the dyslipidaemia simvastatin had no impact on kidney function or urinary albumin excretion rate and did not reduce insulin resistance in these microalbuminuric and moderately hypercholesterolaemic Type 2 diabetic patients CONTEXT Hypertension is associated with a significantly increased risk of morbidity and mortality . Only diuretics and beta-blockers have been shown to reduce this risk in long-term clinical trials . Whether newer antihypertensive agents reduce the incidence of cardiovascular disease ( CVD ) is unknown . OBJECTIVE To compare the effect of doxazosin , an alpha-blocker , with chlorthalidone , a diuretic , on incidence of CVD in patients with hypertension as part of a study of 4 types of antihypertensive drugs : chlorthalidone , doxazosin , amlodipine , and lisinopril . DESIGN R and omized , double-blind , active-controlled clinical trial , the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial , initiated in February 1994 . In January 2000 , after an interim analysis , an independent data review committee recommended discontinuing the doxazosin treatment arm based on comparisons with chlorthalidone . Therefore , outcomes data presented herein reflect follow-up through December 1999 . SETTING A total of 625 centers in the United States and Canada . PARTICIPANTS A total of 24,335 patients ( aged > or = 55 years ) with hypertension and at least 1 other coronary heart disease ( CHD ) risk factor who received either doxazosin or chlorthalidone . INTERVENTIONS Participants were r and omly assigned to receive chlorthalidone , 12.5 to 25 mg/d ( n=15,268 ) , or doxazosin , 2 to 8 mg/d ( n=9067 ) , for a planned follow-up of 4 to 8 years . MAIN OUTCOME MEASURES The primary outcome measure was fatal CHD or nonfatal myocardial infa rct ion ( MI ) , analyzed by intent to treat ; secondary outcome measures included all-cause mortality , stroke , and combined CVD ( CHD death , nonfatal MI , stroke , angina , coronary revascularization , congestive heart failure [ CHF ] , and peripheral arterial disease ) ; compared by the chlorthalidone group vs the doxazosin group . RESULTS Median follow-up was 3.3 years . A total of 365 patients in the doxazosin group and 608 in the chlorthalidone group had fatal CHD or nonfatal MI , with no difference in risk between the groups ( relative risk [ RR ] , 1.03 ; 95 % confidence interval [ CI ] , 0.90 - 1.17 ; P=.71 ) . Total mortality did not differ between the doxazosin and chlorthalidone arms ( 4-year rates , 9.62 % and 9.08 % , respectively ; RR , 1.03 ; 95 % CI , 0.90 - 1.15 ; P=.56 . ) The doxazosin arm , compared with the chlorthalidone arm , had a higher risk of stroke ( RR , 1.19 ; 95 % CI , 1.01 - 1.40 ; P=.04 ) and combined CVD ( 4-year rates , 25.45 % vs 21.76 % ; RR , 1.25 ; 95 % CI , 1.17 - 1.33 ; P<.001 ) . Considered separately , CHF risk was doubled ( 4-year rates , 8.13 % vs 4.45 % ; RR , 2.04 ; 95 % CI , 1.79 - 2.32 ; P<.001 ) ; RRs for angina , coronary revascularization , and peripheral arterial disease were 1.16 ( P<.001 ) , 1.15 ( P=.05 ) , and 1.07 ( P=.50 ) , respectively . CONCLUSION Our data indicate that compared with doxazosin , chlorthalidone yields essentially equal risk of CHD death/nonfatal MI but significantly reduces the risk of combined CVD events , particularly CHF , in high-risk hypertensive patients Aims /hypothesisThe aim of this study was to determine the pattern of the effect of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin on cardiovascular events in patients with type 2 diabetes and no prior history of cardiovascular disease ( CVD ) . Material s and methods A post hoc analysis of data from the Collaborative Atorvastatin Diabetes Study ( CARDS ) , a r and omised , placebo-controlled trial of 2,838 patients with type 2 diabetes , was performed . Patients received atorvastatin ( 10 mg daily ) or placebo and were evaluated for cardiovascular and other outcomes over a median follow-up period of 3.9 years . Cox proportional hazards modelling was carried out , and the hazard ratios calculated for various times after r and omisation to treatment were investigated . Results A reduction in the primary endpoint of major CVD events was apparent and statistically significant as soon as 18 months after treatment initiation . The effect of atorvastatin on CHD events was apparent by 6 months , and at 1 year was similar to the 37 % relative risk reduction observed at trial closure . Conclusions /interpretationAtorvastatin alters the pathogenesis of CVD rapidly , such that the effect on cardiovascular events is apparent within months of initiation of therapy OBJECTIVE Statins have been hypothesized to slow loss of kidney function , however , data is conflicting . This study assessed whether simvastatin reduces rates of kidney function loss in participants with coronary heart disease ( CHD ) . METHODS We performed a post hoc analysis from the Sc and inavian Simvastatin Survival Study , a r and omized trial of simvastatin vs. placebo in 4444 men and women with CHD . Kidney disease progression defined as the occurrence of a > or=25 % reduction in estimated glomerular filtration rate ( GFR ) from baseline or development of chronic kidney disease ( CKD ) , defined as estimated GFR < 60 mL/min/1.73 m(2 ) . The annual rate of change in estimated GFR was also evaluated . Estimated GFR was determined by the Modified Diet and Renal Disease Study equation . RESULTS Change in kidney function could be calculated in 3842 subjects , of whom 409 had CKD at baseline . In the whole population , simvastatin significantly reduced the frequency of a > or=25 % decline in kidney function [ adjusted odds ratio ( OR ) 0.68 , 95 % confidence interval ( CI ) , 0.50 - 0.92 ; p=0.01 ] during 5.5 years of follow-up . The adjusted annualized least-square mean decline in estimated GFR in the simvastatin group was lower than that in the placebo group ( 0.34 mL/min/1.73 m(2)/year vs. 0.41 mL/min/1.73 m(2)/year , respectively ; p=0.02 ) . There was no significant effect of simvastatin on kidney function in the subgroup of participants ( n=363 ) , who developed incident CKD at the end of follow-up [ adjusted OR : 0.89 ( 95 % CI 0.70 - 1.14 ; p=0.36 ) ] . CONCLUSION Simvastatin was associated with a moderate protective effect on the rate of kidney function loss in participants with CHD Objective The FGB gene codes for fibrinogen-&bgr ; , a polypeptide of the coagulation factor fibrinogen , which is positively associated with cardiovascular diseases . Studies show that angiotensin-converting enzyme ( ACE ) inhibitors lower plasma fibrinogen concentrations , whereas diuretics and calcium-channel blockers do not . As carriers of the FGB-455 minor ‘ A ’ allele have higher levels of fibrinogen while ACE inhibitors lower it , we hypothesize that ‘ A ’ allele carriers benefit more from antihypertensive treatment with ACE inhibitors than calcium-channel blockers or diuretics , relative to ‘ GG ’ genotype individuals . Methods The Genetics of Hypertension Associated Treatment ( GenHAT ) study [ ancillary to Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) ] genotyped hypertensive participants for several hypertension-related c and i date genes , making this a post-hoc analysis of a r and omized trial . In total , 90.1 % of the ALLHAT population was successfully genotyped for FGB-455 . We included participants ( n=30 076 ) r and omized to one of three antihypertensive medications ( lisinopril , amlodipine , chlorthalidone ) , with two treatment comparisons : lisinopril versus chlorthalidone and lisinopril versus amlodipine . The primary outcome of ALLHAT/GenHAT was coronary heart disease , defined as fatal coronary heart disease or non-fatal myocardial infa rct ion , and secondary outcomes included stroke , heart failure , all-cause mortality , and end-stage renal disease ( ESRD ) with mean follow-up time of 4.9 years . Genotype-by-treatment interactions ( pharmacogenetic effects ) were tested with the Cox regression . Results Stroke : common ‘ GG ’ homozygotes had higher risk on lisinopril versus amlodipine [ hazard ratio (HR)=1.38 , P<0.001 ] , whereas minor ‘ A ’ allele carriers had slightly lower risk ( HR=0.96 , P=0.76 ; P value for interaction=0.03 ) . Mortality : ‘ GG ’ homozygotes had higher risk on lisinopril versus amlodipine ( HR=1.12 , P=0.02 ) or chlorthalidone ( 1.05 , P=0.23 ) , whereas ‘ A ’ allele carriers had slightly lower risk ( HR=0.92 , P=0.33 for lisinopril versus amlodipine ; HR=0.88 , P=0.08 for lisinopril versus chlorthalidone ; P value for interactions 0.04 and 0.03 , respectively ) . ESRD : ‘ GG ’ homozygotes had higher risk on lisinopril versus chlorthalidone ( HR=1.27 , P=0.08 ) , whereas ‘ A ’ allele carriers had lower risk ( HR=0.64 , P=0.12 ; P value for interaction=0.03 ) . Conclusion There was evidence of pharmacogenetic effects of FGB-455 on stroke , ESRD , and mortality , suggesting that relative to those homozygous for the common allele , variant allele carriers of the FGB gene at position −455 have a better outcome if r and omized to lisinopril than chlorthalidone ( for mortality and ESRD ) or amlodipine ( for mortality and stroke ) . For the models in which a pharmacogenetic effect was observed , the outcome rates among ‘ GG ’ homozygotes were higher in those r and omized to lisinopril versus amlodipine or chlorthalidone , whereas minor ‘ A ’ allele carriers had lower event rates when r and omized to lisinopril versus the other medications Experimental evidence and several small studies in humans suggest that HMG-CoA ( 3-hydroxy 3-methylglutaryl coenzyme A ) reductase inhibitors ( statins ) reduce blood pressure , perhaps through effects on endothelial function or by reducing inflammation . We tested the hypothesis that pravastatin would reduce blood pressure at 3 months and the risk of developing new hypertension over a follow-up period of 5 years . This was a post hoc subgroup analysis of a r and omized double-blind placebo-controlled trial of pravastatin 40 mg daily vs placebo in 4159 participants with previous myocardial infa rct ion and total plasma cholesterol < 240 mg/dl ( 6.2 mmol/l ) . The primary outcome was the unadjusted change in mean arterial pressure ( MAP ) from baseline to 3 months . We also considered systolic and diastolic blood pressure ( SBP and DBP ) and pulse pressure . Analysis of covariance was used to calculate the adjusted effect of treatment on change in these outcomes at 3 , 6 , 12 and 24 months postr and omization , after controlling for potential confounders . Logistic regression was used to calculate the adjusted effect of treatment on incident hypertension ( blood pressure ⩾140/90 in those without known hypertension at baseline ) . This analysis included 4126/4159 ( 99.2 % ) participants for whom blood pressure was measured at baseline and during at least one follow-up visit . Median duration of follow-up was 57.8 months . The unadjusted and adjusted change in MAP , SBP , DBP or pulse pressure from baseline was not significantly different for pravastatin or placebo recipients at 3 , 6 , 12 or 24 months after r and omization , or at last follow-up . Pravastatin did not reduce the adjusted risk of incident systolic hypertension ( odds ratio 0.99 , 95 % CI 0.80–1.23 ) , or incident diastolic hypertension ( odds ratio 0.97 , 95 % CI 0.73–1.27 ) . In summary , pravastatin 40 mg daily did not reduce blood pressure in survivors of myocardial infa rct ion without overt hypercholesterolaemia BACKGROUND Evidence -based treatment for hypercholesterolaemia in Japan has been hindered by the lack of direct evidence in this population . Our aim was to assess whether evidence for treatment with statins derived from western population s can be extrapolated to the Japanese population . METHODS In this prospect i ve , r and omised , open-labelled , blinded study , patients with hypercholesterolaemia ( total cholesterol 5.69 - 6.98 mmol/L ) and no history of coronary heart disease or stroke were r and omly assigned diet or diet plus 10 - 20 mg pravastatin daily . The primary endpoint was the first occurrence of coronary heart disease . Statistical analyses were done by intention to treat . This trial is registered at Clinical Trials.gov , number NCT00211705 . FINDINGS 3966 patients were r and omly assigned to the diet group and 3866 to the diet plus pravastatin group . Mean follow-up was 5.3 years . At the end of study , 471 and 522 patients had withdrawn , died , or been lost to follow-up in the diet and diet plus pravastatin groups , respectively . Mean total cholesterol was reduced by 2.1 % ( from 6.27 mmol/L to 6.13 mmol/L ) and 11.5 % ( from 6.27 mmol/L to 5.55 mmol/L ) and mean LDL cholesterol by 3.2 % ( from 4.05 mmol/L to 3.90 mmol/L ) and 18.0 % ( from 4.05 mmol/L to 3.31 mmol/L ) in the diet and the diet plus pravastatin groups , respectively . Coronary heart disease was significantly lower in the diet plus pravastatin group than in the diet alone group ( 66 events vs 101 events ; HR 0.67 , 95 % CI 0.49 - 0.91 ; p=0.01 ) . There was no difference in the incidence of malignant neoplasms or other serious adverse events between the two groups . INTERPRETATION Treatment with a low dose of pravastatin reduces the risk of coronary heart disease in Japan by much the same amount as higher doses have shown in Europe and the USA BACKGROUND The West of Scotl and Coronary Prevention Study was a r and omized clinical trial comparing pravastatin with placebo in men with hypercholesterolemia who did not have a history of myocardial infa rct ion , with an average follow-up of approximately 5 years . The combined outcome of death from definite coronary heart disease or definite nonfatal myocardial infa rct ion was reduced from 7.9 to 5.5 % ( P<0.001 ) in the treatment group . Extended follow-up data were obtained for approximately 10 years after completion of the trial . METHODS For the survivors of the trial , all deaths , hospitalizations and deaths due to coronary events and stroke , and incident cancers and deaths from cancer were tracked with the use of a national computerized record-linkage system . The results were analyzed with time-to-event analyses and use of Cox proportional-hazards models . RESULTS Five years after the trial ended , 38.7 % of the original statin group and 35.2 % of the original placebo group were being treated with a statin . In the period approximately 10 years after completion of the trial , the risk of death from coronary heart disease or nonfatal myocardial infa rct ion was 10.3 % in the placebo group and 8.6 % in the pravastatin group ( P=0.02 ) ; over the entire follow-up period , the rate was 15.5 % in the placebo group and 11.8 % in the pravastatin group ( P<0.001 ) . Similar percentage reductions were seen in the combined rate of death from coronary heart disease and hospitalization for coronary events for both periods . The rate of death from cardiovascular causes was reduced ( P=0.01 ) , as was the rate of death from any cause ( P=0.03 ) , over the entire follow-up period . There were no excess deaths from noncardiovascular causes or excess fatal or incident cancers . CONCLUSIONS In this analysis , 5 years of treatment with pravastatin was associated with a significant reduction in coronary events for a subsequent 10 years in men with hypercholesterolemia who did not have a history of myocardial infa rct ion OBJECTIVE Liver-type fatty acid-binding protein ( l-FABP ) is expressed in renal proximal tubules and is reported to be a useful marker for progression of chronic glomerulonephritis . The aim of this study was to determine whether urinary l-FABP levels are altered at various stages of diabetic nephropathy and whether pitavastatin affects urinary l-FABP levels in early diabetic nephropathy . RESEARCH DESIGN AND METHODS Fifty-eight patients with type 2 diabetes ( 34 men and 24 women , median age 52 years ) and 20 healthy , age-matched subjects ( group E ) were recruited for the study . The diabetic patients included 12 patients without nephropathy ( group A ) , 20 patients with microalbuminuria ( group B ) , 14 patients with macroalbuminuria and normal renal function ( group C ) , and 12 patients with chronic renal failure but not undergoing hemodialysis ( blood creatinine > 1.2 mg/dl ; mean 2.5 mg/dl , group D ) . Twenty group B patients were r and omly assigned to receive 1 mg/day pitavastatin ( 10 patients , group B1 ) or placebo ( 10 patients , group B2 ) . Treatment was continued for 12 months . Urinary l-FABP levels were measured by enzyme-linked immunosorbent assay . Urinary 8-hydroxydeoxyguanosine and serum free fatty acids ( FFAs ) were also measured in group B. RESULTS Urinary l-FABP levels in groups A-D were 6.2 + /- 4.6 microg/g creatinine , 19.6 + /- 13.5 microg/g creatinine , 26.8 + /- 20.4 microg/g creatinine , and 52.4 + /- 46.8 microg/g creatinine , respectively . Urinary l-FABP levels in groups B-D were significantly higher than those in healthy subjects ( group E , 5.8 + /- 4.0 microg/g creatinine ) ( group B , P < 0.05 ; group C , P < 0.01 ; group D , P < 0.01 ) . In group B1 , urinary albumin excretion ( UAE ) and urinary l-FABP levels were decreased after pitavastatin treatment ( UAE before , 110 + /- 74 microg/min ; 6 months , 88 + /- 60 microg/min , P < 0.05 ; 12 months , 58 + /- 32 microg/min , P < 0.01 ; l-FABP before , 18.6 + /- 12.5 microg/g creatinine ; 6 months , 12.2 + /- 8.8 microg/g creatinine , P < 0.05 ; 12 months , 8.8 + /- 6.4 microg/g creatinine , P < 0.01 ) . In group B2 , UAE and l-FABP levels showed little change during the experimental period . In group B1 , urinary 8-hydroxydeoxyguanosine was decreased 12 months after pitavastatin treatment ( before 32.5 + /- 19.5 ng/mg creatinine , after 18.8 + /- 14.5 ng/mg creatinine , P < 0.01 ) , but in group B2 , these showed little difference during the experimental period . In both groups B1 and B2 , serum FFAs showed little difference during the experimental period . CONCLUSIONS Urinary l-FABP levels appear to be associated with the progression of diabetic nephropathy , and pitavastatin may be effective in ameliorating tubulointerstitial damage in early diabetic nephropathy BACKGROUND Patients with renal insufficiency have an increased risk of cardiovascular disease that is not fully explained by the presence of known cardiovascular risk factors . In patients with end-stage renal disease , increased serum concentration of asymmetric dimethylarginine ( ADMA ) , an endogenous inhibitor of nitric oxide synthase ( NOS ) , has been linked to excess cardiovascular morbidity . We investigated , in patients with mild-to-moderate renal failure , the relationship between plasma ADMA and three surrogate markers of atherosclerosis that have been shown to have prognostic value , namely carotid intima-media thickness ( IMT ) , plasma soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) , and plasma C-reactive protein ( CRP ) . METHODS We used baseline data of an ongoing r and omized trial in which the effects of oxidative stress-lowering treatment on vascular function and structure are studied in patients with chronic nondiabetic renal failure without clinical evidence of atherosclerosis ( GFR 15 to 70 mL/min/per 1.73 m(2 ) according to the Cockcroft-Gault equation ; ATIC study ) . RESULTS Data from 93 patients were used . Creatinine clearance was inversely related to plasma ADMA concentration ( st and ardized beta after adjustment = -0.342 , P = 0.023 ) . Plasma ADMA was strongly related to carotid IMT in univariate ( beta = 0.459 , P < 0.0001 ) and multivariate analysis ( beta= 0.444 , P < 0.0001 ) . Plasma ADMA was also significantly related with plasma soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) in univariate ( beta = 0.260 , P = 0.010 ) and multivariate ( beta = 0.242 , P = 0.022 ) analysis . Plasma ADMA was not significantly related to C-reactive protein ( beta = -0.134 , P = 0.204 ) . CONCLUSION In patients with mild-to-moderate renal failure , renal function is inversely associated with plasma ADMA , which , in turn , is positively associated with carotid IMT and plasma sVCAM-1 concentration . Increased plasma ADMA may be a link between renal function and cardiovascular disease in patients with mild-to-moderate renal failure In a double-blind , placebo-controlled , r and omized crossover study , 15 stable mild hyperglycemic patients without treatment and with features of metabolic syndrome were treated with cerivastatin ( 0.4 mg/day ) or placebo for 3 months . The insulin sensitivity index during the euglycemic-hyperinsulinemic clamp ( EHC ; 5.4 mmol/l ; 80 mU x m(-2 ) x min(-1 ) ) was increased by cerivastatin treatment ( 66.39 + /- 3.9 nmol x lean body mass [LBM](-1 ) x min(-1 ) x pmol(-1 ) x l(-1 ) ) as compared with placebo ( 58.37 + /- 3.69 nmol x LBM(-1 ) x min(-1 ) x pmol(-1 ) x l(- 1 ) ; P < 0.01 ) by 13.7 % . Glucose oxidation during EHC was significantly higher with statin treatment ( 16.1 + /- 1.37 micromol x LBM(-1 ) x min(-1 ) ) as compared with placebo ( 14.58 + /- 1.48 micromol x LBM(-1 ) x min(-1 ) ; P < 0.05 ) . During hyperinsulinemia ( approximately 800 pmol/l ) in EHC steady-state , lipid oxidation was significantly decreased and respiratory quotient was significantly increased with statin treatment ( 0.33 + /- 0.05 mg x LBM(-1 ) x min(- 1 ) , 0.94 + /- 0.01 ) as compared with placebo ( 0.48 + /- 0.06 mg x LBM(-1 ) x min(-1 ) , 0.91 + /- 0.01 ; P < 0.01 and P < 0.05 , respectively ) . During statin treatment , the first-phase insulin response increased from 2.07 + /- 0.28 to 2.82 + /- 0.38 pmol x l(-1 ) x pmol(-1 ) ( P < 0.05 ) . The second phase of insulin responses examined by C-peptide and insulin levels averaged during the hyperglycemic clamp ( 20 mmol/l ) was unchanged . In conclusion , this study demonstrates that 0.4 mg cerivastatin therapy improves first-phase insulin secretion and increases insulin-mediated glucose uptake and respiratory quotient in the early state of obese type 2 diabetes AIMS To assess the effects of pravastatin on all-cause mortality and cause-specific mortality and to compare the effects for patients with prior coronary heart disease with those for patients without , using pooled data from the Long-Term Intervention with Pravastatin in Ischaemic Disease ( LIPID ) study , the Cholesterol and Recurrent Events ( CARE ) study , and the West of Scotl and Coronary Prevention Study ( WOSCOPS ) . METHODS AND RESULTS 13 173 patients with coronary heart disease and 6595 men with elevated cholesterol and no prior coronary disease received pravastatin , 40 mg daily , or placebo for an average of 5 to 6 years . Data were analysed according to a pre-specified , published protocol . For all three trials combined , the mortality among patients assigned pravastatin was significantly lower , at 7.9 % , than the 9.8 % among those assigned placebo , a relative risk reduction of 20 % ( 95 % confidence interval ( CI ) 12 - 27 % , P<0.0001 ) . Active treatment was associated with a reduction in coronary mortality ( 24 % , 95 % CI 14 - 33 % ) . Larger reductions in absolute risk were estimated in those with prior coronary heart disease than in those without . CONCLUSION Treatment with pravastatin over 5 years reduces all-cause mortality and coronary mortality in patients with and those without a history of coronary heart disease . The size of the benefit was related principally to the baseline risk Background — Low-density lipoprotein ( LDL ) cholesterol is the principal target of lipid-lowering therapy , but recent evidence has suggested more appropriate targets . We compared the relationships of on-treatment levels of LDL cholesterol , non – high-density lipoprotein ( HDL ) cholesterol , and apolipoprotein B , as well as ratios of total/HDL cholesterol , LDL/HDL cholesterol , and apolipoprotein B/A-I , with the occurrence of cardiovascular events in patients receiving statin therapy . Methods and Results — A post hoc analysis was performed that combined data from 2 prospect i ve , r and omized clinical trials in which 10 001 ( “ Treating to New Targets ” ) and 8888 ( “ Incremental Decrease in End Points through Aggressive Lipid Lowering ” ) patients with established coronary heart disease were assigned to usual-dose or high-dose statin treatment . In models with LDL cholesterol , non-HDL cholesterol and apolipoprotein B were positively associated with cardiovascular outcome , whereas a positive relationship with LDL cholesterol was lost . In a model that contained non-HDL cholesterol and apolipoprotein B , neither was significant owing to collinearity . Total/HDL cholesterol ratio and the apolipoprotein B/A-I ratio in particular were each more closely associated with outcome than any of the individual proatherogenic lipoprotein parameters . Conclusions — In patients receiving statin therapy , on-treatment levels of non-HDL cholesterol and apolipoprotein B were more closely associated with cardiovascular outcome than levels of LDL cholesterol . Inclusion of measurements of the antiatherogenic lipoprotein fraction further strengthened the relationships . These data support the use of non-HDL cholesterol or apolipoprotein B as novel treatment targets for statin therapy . Given the absence of interventions that have been proven to consistently reduce cardiovascular disease risk through raising plasma levels of HDL cholesterol or apolipoprotein A-I , it seems premature to consider the ratio variables as clinical ly useful AIMS The aim of this study was to determine the outcome benefits in those originally assigned atorvastatin in the Anglo-Sc and inavian Cardiac Outcomes Trial-8 years after closure of the lipid-lowering arm ( LLA ) of the trial ( ASCOT-LLA ) among the U.K. population . METHODS AND RESULTS ASCOT-LLA was a factorially design ed double-blind placebo-controlled trial of atorvastatin in 10 305 hypertensive patients enrolled into the ASCOT-Blood Pressure Lowering Arm ( BPLA ) of the trial and with total cholesterol concentrations , at baseline , of < 6.5 mmol/L. ASCOT-LLA was stopped prematurely after a median 3.3-year follow-up because of a 36 % relative risk reduction ( RRR ) in non-fatal myocardial infa rct ion and fatal coronary heart disease ( CHD ) ( the primary outcome ) in favour of atorvastatin and a non-significant reduction in CV deaths ( 16 % ) and all-cause mortality ( 13 % ) . After a further 2.2 years at the end of ASCOT-BPLA , despite extensive crossovers from and to statin usage , the RRR in all endpoints remained essentially unchanged . A median 11 years after initial r and omization and ∼8 years after closure of LLA , all-cause mortality ( n=520 and 460 in placebo and atorvastatin , respectively ) remained significantly lower in those originally assigned atorvastatin ( HR 0.86 , CI 0.76 - 0.98 , P=0.02 ) . CV deaths were fewer , but not significant ( HR 0.89 , CI 0.72 - 1.11 , P=0.32 ) and non-CV deaths were significantly lower ( HR 0.85 , CI 0.73 - 0.99 , P=0.03 ) in those formerly assigned atorvastatin attributed to a reduction in deaths due to infection and respiratory illness . CONCLUSION Legacy effects of those originally assigned atorvastatin may contribute to long-term benefits on all-cause mortality . An explanation for long-term benefits on non-CV deaths has not been established OBJECTIVE —The Treating to New Targets study showed that intensive lipid-lowering therapy with atorvastatin 80 mg/day provides significant clinical benefit beyond that afforded by atorvastatin 10 mg/day in patients with stable coronary heart disease ( CHD ) . The objective of our study was to investigate whether similar benefits of high-dose intensive atorvastatin therapy can be achieved in patients with CHD and diabetes . RESEARCH DESIGN AND METHODS —A total of 1,501 patients with diabetes and CHD , with LDL cholesterol levels of < 130 mg/dl , were r and omized to double-blind therapy with either atorvastatin 10 ( n = 753 ) or 80 ( n = 748 ) mg/day . Patients were followed for a median of 4.9 years . The primary end point was the time to first major cardiovascular event , defined as death from CHD , nonfatal non – procedure-related myocardial infa rct ion , resuscitated cardiac arrest , or fatal or nonfatal stroke . RESULTS —End-of-treatment mean LDL cholesterol levels were 98.6 mg/dl with atorvastatin 10 mg and 77.0 mg/dl with atorvastatin 80 mg . A primary event occurred in 135 patients ( 17.9 % ) receiving atorvastatin 10 mg , compared with 103 patients ( 13.8 % ) receiving atorvastatin 80 mg ( hazard ratio 0.75 [ 95 % CI 0.58–0.97 ] , P = 0.026 ) . Significant differences between the groups in favor of atorvastatin 80 mg were also observed for time to cerebrovascular event ( 0.69 [ 0.48–0.98 ] , P = 0.037 ) and any cardiovascular event ( 0.85 [ 0.73–1.00 ] , P = 0.044 ) . There were no significant differences between the treatment groups in the rates of treatment-related adverse events and persistent elevations in liver enzymes . CONCLUSIONS —Among patients with clinical ly evident CHD and diabetes , intensive therapy with atorvastatin 80 mg significantly reduced the rate of major cardiovascular events by 25 % compared with atorvastatin 10 mg BACKGROUND In animal models , HMG-CoA reductase inhibitors were able to improve renal function and endothelium-dependent vascular reactivity . In various experimental renal diseases , including autosomal dominant polycystic kidney disease ( ADPKD ) , HMG-CoA reductase inhibitors improved the rate of decline in renal function . We studied the effect of simvastatin on ADPKD patients . METHODS In a double-blind cross-over study , 10 normocholesterolaemic ADPKD patients were treated in r and om order for 4 weeks with 40 mg simvastatin or placebo daily . After each treatment period , we investigated the effect of simvastatin on renal blood flow and endothelium-dependent vascular reactivity . These periods were separated by a 4-week wash-out period . RESULTS After treatment with simvastatin , glomerular filtration rate ( GFR ) significantly increased from 124+/-4 ml/min to 132+/-6 ml/min ( P<0.05 ) . Simultaneously , effective renal plasma flow ( ERPF ) increased significantly from 494+/-30 ml/min to 619+/-67 ml/min after simvastatin treatment ( P<0.05 ) . These renal effects were accompanied by a significantly enhanced vasodilator response to acetylcholine in the forearm after simvastatin treatment . Total serum cholesterol levels were significantly reduced after treatment with simvastatin , from 4.24+/-0.32 to 3.17+/-0.22 mmol/l ( P<0.001 ) . CONCLUSION We concluded that simvastatin treatment can ameliorate renal function in ADPKD patients , by increasing renal plasma flow , possibly via improvement of endothelial function . Long-term clinical trials with HMG-CoA reductase inhibitors are needed to confirm these results and to establish a chronic inhibiting effect of HMG-CoA reductase inhibitors on the progression towards end-stage renal disease in ADPKD patients Background Previous trials have had insufficient numbers of coronary events to address definitively the effect of lipid-modifying therapy on coronary heart disease in subgroups of patients with varying baseline characteristics . Methods and Results The data from 3 large r and omized trials with pravastatin 40 mg were pooled and analyzed with the use of a prospect ively defined protocol . Included were 19 768 patients , 102 559 person-years of follow-up , 2194 primary end points ( coronary death or nonfatal myocardial infa rct ion ) , and 3717 exp and ed end points ( primary end point , CABG , or PTCA ) . Pravastatin significantly reduced relative risk in younger ( < 65 years ) and older ( ≥65 years ) patients , men and women , smokers and nonsmokers , and patients with or without diabetes or hypertension . The relative effect was smaller , but absolute risk reduction was similar in patients with hypertension compared with those without hypertension . Relative risk reduction was significant in predefined categories of baseline lipid concentrations . Tests for interaction were not significant between relative risk reduction and baseline total cholesterol ( 5 % to 95 % range 177 to 297 mg/dL , 4.6 to 7.7 mmol/L ) , HDL cholesterol ( 27 to 58 mg/dL , 0.7 to 1.5 mmol/L ) , and triglyceride ( 74 to 302 mg/dL , 0.8 to 3.4 mmol/L ) concentrations , analyzed as continuous variables . However , for LDL cholesterol , the probability values for interaction were 0.068 for the prespecified primary end point and 0.019 for the exp and ed end point . Relative risk reduction was similar throughout most of the baseline LDL cholesterol range ( 125 to 212 mg/dL , 3.2 to 5.5 mmol/L ) with the possible exception of the lowest quintile of CARE/LIPID ( < 125 mg/dL ) ( relative risk reduction 5 % , 95 % CI 19 % to −12 % ) . Conclusions Pravastatin treatment is effective in reducing coronary heart disease events in patients with high or low risk factor status and across a wide range of pretreatment lipid concentrations BACKGROUND The beneficial effects of statins in reducing cardiovascular events have been attributed predominantly to their lipid-lowering effects , recent studies suggest that these effects might be due to their anti-inflammatory properties . We here investigate the in vivo and in vitro effects of simvastatin on cytokine production in pre-dialysis chronic renal failure patients . METHODS Our clinical study has been design ed as a r and omized double-blind placebo controlled study . A total of 55 chronic kidney disease ( CKD ) patients at stages 3 and 4 ( mean creatinine clearance 45 ml/min , range 15 - 60 ) were r and omly assigned to receive simvastatin 40 mg/day or placebo , added to their ongoing treatment , for 6 months . Blood sample s were obtained at baseline , and after 3 and 6 months of observation for the determination of lipids , inflammatory markers and renal function . For the in vitro studies , the effect of increasing doses of simvastatin on cytokine production [ namely interleukin (IL)-6 and IL-8 ] in human cultured monocytes from 10 healthy subjects ( HS ) and 15 CKD patients stimulated by lipopolysaccharide ( LPS ) was investigated . RESULTS A significant reduction in total cholesterol from 221+/-44 mg/dl to 184+/-41 mg/dl ( 3 months ) and to 186+/-39 mg/dl ( 6 months ) ( P<0.02 ) and low-density lipoprotein cholesterol from 139+/-40 mg/dl to 104+/-29 mg/dl ( 3 months ) and to 100+/-31 mg/dl ( 6 months ) ( P<0.001 ) was observed in the 28 patients treated with simvastatin . In this group , C-reactive protein ( CRP ) levels significantly decreased from 2.6 mg/l [ interquartile range ( IQR 4.9 ) ] to 2.0 mg/l ( IQR 1.9 ) ( P = 0.03 ) at 6 months ( P<0.05 ) . A parallel reduction of IL-6 levels from 5.1 pg/ml ( IQR 3.8 ) to 3.5 pg/ml ( IQR 3.1 ) ( P = 0.001 ) at 6 months was also observed . No significant reduction in inflammatory markers [ CRP from 5.1 mg/l ( IQR 1.9 ) to 5.4 mg/l ( IQR 1.3 ) ( P = NS ) at 6 months ] or plasma lipids [ LDL-cholesterol from 127+/-32 mg/dl to 131+/-21 mg/dl ( 6 months ) ] was observed in the 27 patients of the placebo group . In the in vitro studies , the average value for cell-associated IL-6 and IL-8 was higher in CKD ( 155+/-95 pg/ml monocytes for IL-6 and 722+/-921 pg/ml monocytes for IL-8 ) vs HS ( 137+/-87 pg/ml monocytes and 186+/-125 pg/ml monocytes ) ( P<0.01 ) and was not affected by simvastatin alone . LPS result ed in a significant increase in cytokine production ( IL-6 : 1954+/-321 pg/ml monocytes for CKD and 1451+/-237 pg/ml monocytes for HS ; P<0.001 ) ; the simultaneous addition of increasing doses of simvastatin to these cultures induced a dose-dependent inhibition of IL-6 and IL-8 production in stimulated peripheral blood mononuclear cells in all groups . CONCLUSIONS These results indicate that simvastatin in commonly used doses has an in vitro and in vivo anti-inflammatory effect in CKD patients , and may play an important role in counteracting the mechanisms involved on the pathogenesis of cardiovascular disease BACKGROUND Statins improve cardiovascular outcome , but less is known on the renal outcome . We , therefore , studied the relationship between the use of statins and urinary albumin excretion ( UAE ) and glomerular filtration rate ( GFR ) in two setting s : a r and omized controlled trial ( RCT ) and an observational cohort study , in which patients were included to study the impact of an elevated UAE on renal and cardiovascular prognosis . METHODS We used data from the Prevention of REnal and Vascular ENd-stage Disease Intervention trial ( PREVEND-IT ) and the PREVEND cohort study . The PREVEND-IT subjects ( 788 with a UAE 15 - 300 mg/day ) received pravastatin 40 mg/day vs placebo and /or fosinopril 20 mg/day vs placebo in a 2x2 factorial- RCT design . Of the 3440 cohort subjects , 469 used statins during the 4-year follow-up period . Multivariate-regression adjusted for confounding factors and the propensity score was used to estimate the relation between statin use and UAE and GFR . RESULTS In the RCT , pravastatin did not change UAE or GFR , neither in fosinopril yes/no subgroups . In the observational cohort , statin use was associated with a rise in UAE ( + 12.1 % ) , compared with statin non-use ( + 3.6 % , P<0.001 ) . This rise was most pronounced in those on statins prior to the first screening [ + 24.8 % ( 95 % CI : 11.9 - 39.2 ) ] , those using statins>3 years [ + 18.5 % ( 7.3 - 30.8 ) ] and those with > 1 or > 2 defined daily doses ( + 15.7 and + 17.3 % , respectively ) . These differences remained significant after adjustment for relevant variables and propensity score . The rise in UAE could not be attributed to a higher dose or a specific statin . GFR fell in 4 years in both statin users and non-users ( 4.6+/-13.5 and 2.4+/-11.2 , respectively ) . The fall in GFR between groups was not different after adjustment ( P=0.11 ) . CONCLUSIONS We conclude from the RCT data that statins do not lower UAE in subjects selected because of an elevated UAE instead of hyperlipidaemia . In the observational cohort study , the use of statins similarly was not associated with a fall in UAE ; UAE instead increased . Statin treatment was not associated with a significant change in GFR in these subjects with only modestly impaired GFR BACKGROUND Chronic kidney diseases , particularly if presenting with significant proteinuria , are commonly associated with substantial alteration of serum lipid levels . Experimental evidence suggests that lipid abnormalities may contribute to the progression of kidney disease . However , studies in humans on the subject are scarce . METHODS In a prospect i ve , controlled open-label study , the authors have evaluated the effects of one-year treatment with atorvastatin , a 3-hydroxy-3-methyglutaryl coenzyme A ( HMG-CoA ) reductase inhibitor , versus no treatment on proteinuria and progression of kidney disease in 56 patients with chronic kidney disease . Before r and omization , all patients had already been treated for one year with angiotensin-converting enzyme ( ACE ) inhibitors or angiotensin AT1 receptor antagonists ( ARBs ) and other antihypertensive drugs . RESULTS By the end of one-year treatment , urine protein excretion decreased from 2.2 + /- 0.1 to 1.2 + /- 1.0 g every 24 hours ( P < 0.01 ) in patients treated with atorvastatin in addition to ACE inhibitor and ARBs . By contrast , urinary protein excretion decreased only from 2.0 + /- 0.1 to 1.8 + /- 0.1 g every 24 hours ( P value not significant ) in patients who did not receive atorvastatin in addition to ACE inhibitor or ARBs . During this time , creatinine clearance decreased only slightly and not significantly ( from 51 + /- 1.8 to 49.8 + /- 1.7 ) in patients treated with atorvastatin . By contrast , during the same period of observation , creatinine clearance decreased from 50 + /- 1.9 to 44.2 + /- 1.6 mL/min ( P < 0.01 ) in patients who did not receive atorvastatin . CONCLUSIONS This study has shown that treatment with atorvastatin in addition to a regimen with ACE inhibitors or ARBs may reduce proteinuria and the rate of progression of kidney disease in patients with chronic kidney disease , proteinuria , and hypercholesterolemia . The benefits appear to occur in addition to those of treatment with ACE inhibitor and ARBs Objective : To investigate the relationships between plasma leptin and adiponectin levels and recurrent cardiovascular events ( cardiovascular death , nonfatal myocardial infa rct ion and stroke ) in men with earlier acute coronary syndromes . Design , subjects and measurements : A nested case – control study examined circulating leptin and adiponectin levels in plasma obtained 4–6 years after entry into the Long-Term Intervention with Pravastatin in Ischaemic Disease ( LIPID ) trial . Plasma was assayed from 184 men who suffered recurrent events within 4.4 years after blood collection and 184 matched controls who remained free of further events . The association between cardiovascular events and the explanatory variables was examined by conditional logistic regression analysis . Results : Relative risk ( RR ) increased across increasing leptin quartiles ; the highest quartile compared with the lowest quartile was related to the highest risk ( P for trend=0.002 ) ; the increased risk remained after adjustment for risk factors ( P=0.018 ) or for obesity ( P=0.038 ) , but in the final model ( adjusted for r and omized treatment , other drugs , LIPID risk score , age and body mass index ) , the risk was attenuated ( RR=1.61 , 95 % CI : 0.72–3.57 , P for trend=0.34 ) . Adiponectin did not predict cardiovascular events . Subjects r and omly allocated to pravastatin had 6 % lower leptin levels ( P=0.04 ) than those allocated to placebo . Conclusion : Plasma leptin was a significant and independent predictor of recurrent cardiovascular events ( cardiovascular death , nonfatal myocardial infa rct ion and stroke ) in men with earlier acute coronary syndromes Despite extensive knowledge about abnormal lipid patterns in patients with end-stage renal disease , the association between cholesterol and the development of renal dysfunction is unclear . We evaluated this association in a prospect i ve cohort study among 4,483 initially healthy men participating in the Physicians ' Health Study who provided blood sample s in 1982 and 1996 . Main outcome measures were elevated creatinine , defined as > /= 1.5 mg/dl ( 133 micromol/L ) , and reduced estimated creatinine clearance , defined as < /=55 ml/min . Cholesterol parameters included total cholesterol ( < 200 , 200 to 239 , and > /= 240 mg/dl ) , HDL ( < 40 or > /= 40 mg/dl ) , total non-HDL cholesterol , and the ratio of total cholesterol to HDL . We used logistic regression to calculate age- and multivariable adjusted odds ratios as a measure for the relative risk . After 14 yr , 134 men ( 3.0 % ) had elevated creatinine and 244 ( 5.4 % ) had reduced creatinine clearance . The multivariable relative risk for elevated creatinine was 1.77 ( 95 % confidence interval [ CI ] , 1.10 to 2.86 ) for total cholesterol > /= 240 mg/dl , 2.16 ( 95 % CI , 1.42 to 3.27 ) for HDL < 40 mg/dl , 2.34 ( 95 % CI , 1.34 to 4.07 ) for the highest quartile of total cholesterol/HDL ratio ( > /= > 6.8 ) , and 2.16 ( 95 % CI , 1.22 to 3.80 ) for the highest quartile of non-HDL cholesterol ( > /= 196.1 ) . Similar although smaller associations were observed between cholesterol parameters and reduced creatinine clearance . Elevated total cholesterol , high non-HDL cholesterol , a high ratio of total cholesterol/HDL , and low HDL in particular were significantly associated with an increased risk of developing renal dysfunction in men with an initial creatinine < 1.5 mg/dl Context Are statins effective and safe in patients with renal insufficiency ? Contribution This subgroup analysis of a large r and omized , double-blind , placebo-controlled trial shows that pravastatin reduces risk for future cardiovascular events in men and women with recent myocardial infa rct ion , total cholesterol level less than 6.21 mmol/L ( 240 mg/dL ) , and mild renal insufficiency . Adverse events were few and were similar in nature and frequency to those that have been reported in patients without renal insufficiency . Implication s Pravastatin appears to be safe and effective for secondary prevention of cardiovascular events in patients with mild chronic renal insufficiency . The Editors Chronic renal insufficiency is a common condition that may affect as many as 6 million Americans ( 1 ) and is associated with high rates of cardiovascular disease . Regardless of diabetic status , persons with chronic renal insufficiency have cardiovascular mortality rates at least 10 times higher than the general population ( 2 ) . This excess burden of illness appears to be due to a higher prevalence of traditional cardiovascular risks ( 3 - 5 ) and possibly also to nontraditional risk factors , such as homocysteinemia , hyperparathyroidism , and chronic inflammation ( 6 , 7 ) . Chronic renal insufficiency encompasses all levels of renal dysfunction , up to and including dialysis dependence , but an emerging body of literature suggests that even very mild renal disease increases cardiovascular risk ( 8 - 10 ) . Although there is no universally accepted definition of chronic renal insufficiency , previous studies on cardiovascular disease have used creatinine clearance less than or equal to 75 mL/min to identify persons with this condition ( 11 , 12 ) . Drugs that inhibit 3-hydroxy-3methylglutaryl coenzyme A reductase ( statins ) are known to reduce mortality in hyperlipidemic persons with coronary disease in the general population ( 13 ) . However , no published information is available about the efficacy of statins in persons who also have chronic renal insufficiency . Surprisingly , the prevalence of statin use in this subgroup is less than 25 % ( 11 ) . There is no a priori reason to suspect that statins would be less effective in chronic renal insufficiency ; however , lack of proven efficacy or concerns about toxicity may contribute to nonprescription in patients with this condition . To evaluate the efficacy and safety of pravastatin in chronic renal insufficiency , we analyzed data from a subset of participants in a previously conducted r and omized trial who had a creatinine clearance less than or equal to 75 mL/min . Methods Study Group and Design The design of the Cholesterol and Recurrent Events ( CARE ) trial has been described in detail elsewhere ( 14 ) . Briefly , this was a r and omized , double-blind , placebo-controlled trial in men and postmenopausal women who had had acute myocardial infa rct ion between 3 and 20 months before r and omization and had total plasma cholesterol levels less than 6.21 mmol/L ( < 240 mg/dL ) . Participants with 2 + proteinuria or greater on routine dipstick testing or serum creatinine values more than 1.5 times the upper limit of normal ( as defined by the central study laboratory ) were specifically excluded from the CARE study . After stratification according to clinical center , eligible persons were assigned by computer-generated r and om order to receive 40 mg of pravastatin ( Pravachol , Bristol-Myers Squibb , Princeton , New Jersey ) once daily , or placebo . Treatment allocation was concealed by a central ly maintained code . Participants continued to take all prescribed medication that they were receiving at baseline . All study -specific laboratory measurements were performed at a central facility . Our analysis used the same cardiovascular end points specified by the original CARE trial . The primary end point was death from coronary disease ( including fatal myocardial infa rct ion , sudden death , death during a coronary intervention , and death from other coronary causes ) or a symptomatic nonfatal myocardial infa rct ion confirmed by serum creatine kinase measurements . Secondary end points included major coronary events ( fatal coronary disease , nonfatal myocardial infa rct ion , coronary artery bypass surgery , or coronary angioplasty ) , all-cause mortality , stroke , and coronary revascularization . A committee that was blinded to serum lipid levels and treatment assignment determined outcomes . The adequacy of blinding was not formally assessed . Definitions of Renal Insufficiency The CockcroftGault equation for creatinine clearance is widely used and is known to correlate well with glomerular filtration rate ( 15 ) . We initially selected a creatinine clearance less than or equal to 75 mL/min as our primary definition of mild chronic renal insufficiency . Recently published guidelines suggest defining renal function in terms of an equation derived from the Modification of Diet in Renal Disease ( MDRD ) Study ( 16 ) . This equation expresses glomerular filtration rate in mL/min per 1.73 m2 of body surface area and is defined by 186 PCr 1.154 age in years 0.203 1.210 ( if black ) 0.742 ( if female ) , where PCr is plasma creatinine concentration in mg/dL. Mildly decreased glomerular filtration rate is defined as 60 to 89 mL/min per 1.73 m2 . Although the MDRD equation has not been used as extensively as the CockcroftGault equation , its use is becoming more common . We performed additional analyses by defining mild chronic renal insufficiency as a glomerular filtration rate less than 75 mL/min per 1.73 m2 . Subgroup Analysis We performed several additional analyses to evaluate the potential interactions among pravastatin use , chronic renal insufficiency , and certain subgroups . These subgroups were determined according to published recommendations ( 17 ) and were defined by diabetic status , serum lipid levels at baseline , different levels of renal function , and proteinuria ( defined as detectable protein on routine urine dipstick testing ) . Statistical Analysis All analyses were performed on an intention-to-treat basis ; P values are two sided . The effect of pravastatin on the rate of the primary end point was assessed by using the log-rank test . All other hazard ratios ( HRs ) and associated 95 % CIs were assessed with Cox proportional-hazards models , adjusting for covariates that might confound the relationship between treatment assignment and outcomes . Review of the loglog survival curves for each model showed no evidence that the proportional hazards assumption was violated . There was no evidence of effect modification by center , and stratifying models by center did not affect the results . Analyses were performed by using SAS software , version 8.2 ( SAS Institute , Inc. , Cary , North Carolina ) . Role of the Funding Source The CARE trial and this sub study on renal insufficiency are investigator-initiated studies funded by Bristol-Myers Squibb . The data were collected and analyzed by and are now maintained at the coordinating center at the University of Texas School of Public Health , Houston , Texas . The authors had unlimited access to the data used in this analysis . The sponsor is entitled to comment on manuscripts before su bmi ssion , and the authors may consider these comments , but the rights to publication reside contractually with the investigators . The sponsor maintained information on adverse events and other trial data , as required by federal regulations . Results Baseline Characteristics Of the 4159 persons in the original trial , 1711 had chronic renal insufficiency according to the primary definition ( creatinine clearance 75 mL/min ) ( Figure ) . Participants with renal insufficiency were older , were more likely to be women and to have a history of hypertension or congestive heart failure , and had slightly higher systolic blood pressure than those without renal insufficiency . Dipstick-positive proteinuria was slightly more common in persons with chronic renal insufficiency . Persons with renal insufficiency in the pravastatin and placebo groups were similar at baseline ( Table 1 ) . Figure . Flow of participants through the study . Table 1 . Baseline Characteristics in Participants according to Creatinine Clearance and Treatment Status Adherence to Therapy and Use of Co-Medications Rates of therapy discontinuation between the pravastatin and placebo groups were similar among participants with renal insufficiency ( 46 of 844 participants vs. 54 of 867 participants ; P > 0.2 ) . Rates of use of -adrenergic blockers , aspirin , and angiotensin-converting enzyme inhibitors were similar between treatment groups at baseline and during annual follow-up visits . Angiotensin-receptor antagonists were not widely available when the CARE study was conducted . Cardiovascular Event Rates in Participants with Chronic Renal Insufficiency The cumulative incidence of the primary end point and of major coronary events were similar in persons with and without chronic renal insufficiency . Two hundred fifteen of the 1711 participants with renal insufficiency experienced the primary end point , compared with 271 of the 2448 participants with normal renal function ( 11.1 % ) ( adjusted HR , 1.20 [ 95 % CI , 0.94 to 1.51 ] ) . Participants with chronic renal insufficiency had higher rates of all-cause mortality ( unadjusted HR , 1.63 [ CI , 1.33 to 2.00 ] ) and stroke ( unadjusted HR , 1.98 [ CI , 1.40 to 2.80 ] ) than those without . However , after adjustment for baseline factors , these differences were no longer statistically significant . Pravastatin Use in Chronic Renal Insufficiency Median duration of follow-up was 58.9 months in the participants with chronic renal insufficiency ; complete follow-up data were available for all participants in this subgroup . Persons in the pravastatin group with and without renal insufficiency had similar changes in plasma lipid levels in response to therapy . Among those with renal insufficiency , pravastatin was associated with statistically significant reductions in mean low-density lipoprotein cholesterol level ( by 0.96 BACKGROUND Long-term safety is an important consideration in the selection and use of drugs , such as lipid-lowering agents , that are prescribed to reduce the risk of clinical events during long periods . METHODS The Sc and inavian Simvastatin Survival Study was design ed to evaluate the effects of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease . The 4444 patients aged 35 to 70 years ( mean , 58.9 years ) with angina pectoris or previous myocardial infa rct ion and serum cholesterol levels of 5.5 to 8.0 mmol/L ( 213 - 310 mg/dL ) receiving a lipid-lowering diet were r and omly assigned to take double-blind treatment with simvastatin , 20 to 40 mg once daily , or placebo . In addition to previously reported end-point events , detailed clinical and laboratory safety data were collected during a median follow-up period of 5.4 years ( range in survivors , 4.9 - 6.2 years ) . RESULTS The only clearly drug-related serious adverse event during the 5.4-year median follow-up period was a single reversible case of myopathy . The frequencies of persistent elevations of hepatic aminotransferase levels above 3 times the upper limit of normal and of nonviral hepatitis in the simvastatin and placebo treatment groups were not significantly different . Examination of the lens showed no between-group differences , and no previously unrecognized adverse effects of the drug were observed . There were no significant between-group differences in adverse events in any body system . In particular , the frequency of adverse events related to the central nervous system was similar in both groups . CONCLUSION The safety profile of simvastatin , 20 to 40 mg daily , over 5 years was excellent CONTEXT Evidence suggests that more intensive lowering of low-density lipoprotein cholesterol ( LDL-C ) than is commonly applied clinical ly will provide further benefit in stable coronary artery disease . OBJECTIVE To compare the effects of 2 strategies of lipid lowering on the risk of cardiovascular disease among patients with a previous myocardial infa rct ion ( MI ) . DESIGN , SETTING , AND PARTICIPANTS The IDEAL study , a prospect i ve , r and omized , open-label , blinded end-point evaluation trial conducted at 190 ambulatory cardiology care and specialist practice s in northern Europe between March 1999 and March 2005 with a median follow-up of 4.8 years , which enrolled 8888 patients aged 80 years or younger with a history of acute MI . INTERVENTIONS Patients were r and omly assigned to receive a high dose of atorvastatin ( 80 mg/d ; n = 4439 ) , or usual-dose simvastatin ( 20 mg/d ; n = 4449 ) . MAIN OUTCOME MEASURE Occurrence of a major coronary event , defined as coronary death , confirmed nonfatal acute MI , or cardiac arrest with resuscitation . RESULTS During treatment , mean LDL-C levels were 104 ( SE , 0.3 ) mg/dL in the simvastatin group and 81 ( SE , 0.3 ) mg/dL in the atorvastatin group . A major coronary event occurred in 463 simvastatin patients ( 10.4 % ) and in 411 atorvastatin patients ( 9.3 % ) ( hazard ratio [ HR ] , 0.89 ; 95 % CI , 0.78 - 1.01 ; P = .07 ) . Nonfatal acute MI occurred in 321 ( 7.2 % ) and 267 ( 6.0 % ) in the 2 groups ( HR , 0.83 ; 95 % CI , 0.71 - 0.98 ; P = .02 ) , but no differences were seen in the 2 other components of the primary end point . Major cardiovascular events occurred in 608 and 533 in the 2 groups , respectively ( HR , 0.87 ; 95 % CI , 0.77 - 0.98 ; P = .02 ) . Occurrence of any coronary event was reported in 1059 simvastatin and 898 atorvastatin patients ( HR , 0.84 ; 95 % CI , 0.76 - 0.91 ; P<.001 ) . Noncardiovascular death occurred in 156 ( 3.5 % ) and 143 ( 3.2 % ) in the 2 groups ( HR , 0.92 ; 95 % CI , 0.73 - 1.15 ; P = .47 ) . Death from any cause occurred in 374 ( 8.4 % ) in the simvastatin group and 366 ( 8.2 % ) in the atorvastatin group ( HR , 0.98 ; 95 % CI , 0.85 - 1.13 ; P = .81 ) . Patients in the atorvastatin group had higher rates of drug discontinuation due to nonserious adverse events ; transaminase elevation result ed in 43 ( 1.0 % ) vs 5 ( 0.1 % ) withdrawals ( P<.001 ) . Serious myopathy and rhabdomyolysis were rare in both groups . CONCLUSIONS In this study of patients with previous MI , intensive lowering of LDL-C did not result in a significant reduction in the primary outcome of major coronary events , but did reduce the risk of other composite secondary end points and nonfatal acute MI . There were no differences in cardiovascular or all-cause mortality . Patients with MI may benefit from intensive lowering of LDL-C without an increase in noncardiovascular mortality or other serious adverse reactions . Trial Registration Clinical Trials.gov Identifier : NCT00159835 A r and omized , placebo-controlled trial in diabetic patients receiving hemodialysis showed no effect of atorvastatin on a composite cardiovascular endpoint , but analysis of the component cardiac endpoints suggested that atorvastatin may significantly reduce risk . Because the AURORA ( A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis : An Assessment of Survival and Cardiovascular Events ) trial included patients with and without diabetes , we conducted a post hoc analysis to determine whether rosuvastatin might reduce the risk of cardiac events in diabetic patients receiving hemodialysis . Among the 731 participants with diabetes , traditional risk factors such as LDL-C , smoking , and BP did not associate with cardiac events ( cardiac death and nonfatal myocardial infa rct ion ) . At baseline , only age and high-sensitivity C-reactive protein were independent risk factors for cardiac events . Assignment to rosuvastatin associated with a nonsignificant 16.2 % reduction in risk for the AURORA trial 's composite primary endpoint of cardiac death , nonfatal MI , or fatal or nonfatal stroke ( HR 0.84 ; 95 % CI 0.65 to 1.07 ) . There was no difference in overall stroke , but the rosuvastatin group had more hemorrhagic strokes than the placebo group ( 12 versus two strokes , respectively ; HR , 5.21 ; 95 % CI 1.17 to 23.27 ) . Rosuvastatin treatment significantly reduced the rates of cardiac events by 32 % among patients with diabetes ( HR 0.68 ; 95 % CI 0.51 to 0.90 ) . In conclusion , among hemodialysis patients with diabetes mellitus , rosuvastatin might reduce the risk of fatal and nonfatal cardiac events The Treating to New Targets ( TNT ) study demonstrated that intensive atorvastatin therapy to achieve low-density lipoprotein cholesterol concentrations well below recommended target levels provides an incremental clinical benefit in patients with stable coronary artery disease . This post hoc analysis of the TNT study was conducted to investigate whether this benefit extends to patients with previous percutaneous coronary intervention ( PCI ) . A total of 10,001 patients with clinical ly evident coronary artery disease , including 5,407 patients with previous PCI , were r and omized to atorvastatin 10 or 80 mg/day and followed for a median of 4.9 years . The primary end point was the occurrence of a first major cardiovascular event . Revascularization , a component of a secondary end point , was also examined . In patients with previous PCI , mean low-density lipoprotein cholesterol levels at study end were 79.5 mg/dl in the 80-mg arm and 100.8 mg/dl in the 10-mg arm . First major cardiovascular events occurred in 230 patients ( 8.6 % ) receiving high-dose atorvastatin and 289 patients ( 10.6 % ) receiving low-dose atorvastatin ( hazard ratio 0.79 , 95 % confidence interval 0.67 to 0.94 , p = 0.008 ) . Repeat revascularization during follow-up ( PCI or coronary artery bypass grafting ) was performed in 466 patients ( 17.3 % ) in the 80-mg arm and 624 patients ( 22.9 % ) in the 10-mg arm ( hazard ratio 0.73 , 95 % confidence interval 0.65 to 0.82 , p < 0.0001 ) . In conclusion , intensive lipid lowering to a mean low-density lipoprotein cholesterol level of 79.5 mg/dl ( 2.1 mmol/L ) with atorvastatin 80 mg/day in patients with previous PCI reduces major cardiovascular events by 21 % and repeat revascularizations by 27 % compared with a less intensive lipid-lowering regimen CONTEXT Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease ( CHD ) , it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol ( LDL-C ) in patients without CHD extends to individuals with average serum cholesterol levels , women , and older persons . OBJECTIVE To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinical ly evident atherosclerotic cardiovascular disease with average total cholesterol ( TC ) and LDL-C levels and below-average high-density lipoprotein cholesterol ( HDL-C ) levels . DESIGN A r and omized , double-blind , placebo-controlled trial . SETTING Outpatient clinics in Texas . PARTICIPANTS A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C ( as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [ NHANES ] III ) . Mean ( SD ) TC level was 5.71 ( 0.54 ) mmol/L ( 221 [ 21 ] mg/dL ) ( 51 st percentile ) , mean ( SD ) LDL-C level was 3.89 ( 0.43 ) mmol/L ( 150 [ 17 ] mg/dL ) ( 60th percentile ) , mean ( SD ) HDL-C level was 0.94 ( 0.14 ) mmol/L ( 36 [ 5 ] mg/dL ) for men and 1.03 ( 0.14 ) mmol/L ( 40 [ 5 ] mg/dL ) for women ( 25th and 16th percentiles , respectively ) , and median ( SD ) triglyceride levels were 1.78 ( 0.86 ) mmol/L ( 158 [ 76 ] mg/dL ) ( 63rd percentile ) . INTERVENTION Lovastatin ( 20 - 40 mg daily ) or placebo in addition to a low-saturated fat , low-cholesterol diet . MAIN OUTCOME MEASURES First acute major coronary event defined as fatal or nonfatal myocardial infa rct ion , unstable angina , or sudden cardiac death . RESULTS After an average follow-up of 5.2 years , lovastatin reduced the incidence of first acute major coronary events ( 1 83 vs 116 first events ; relative risk [ RR ] , 0.63 ; 95 % confidence interval [ CI ] , 0.50 - 0.79 ; P<.001 ) , myocardial infa rct ion ( 95 vs 57 myocardial infa rct ions ; RR , 0.60 ; 95 % CI , 0.43 - 0.83 ; P=.002 ) , unstable angina ( 87 vs 60 first unstable angina events ; RR , 0.68 ; 95 % CI , 0.49 - 0.95 ; P=.02 ) , coronary revascularization procedures ( 157 vs 106 procedures ; RR , 0.67 ; 95 % CI , 0.52 - 0.85 ; P=.001 ) , coronary events ( 215 vs 163 coronary events ; RR , 0.75 ; 95 % CI , 0.61 - 0.92 ; P = .006 ) , and cardiovascular events ( 255 vs 194 cardiovascular events ; RR , 0.75 ; 95 % CI , 0.62 - 0.91 ; P = .003 ) . Lovastatin ( 20 - 40 mg daily ) reduced LDL-C by 25 % to 2.96 mmol/L ( 115 mg/dL ) and increased HDL-C by 6 % to 1.02 mmol/L ( 39 mg/dL ) . There were no clinical ly relevant differences in safety parameters between treatment groups . CONCLUSIONS Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels . These findings support the inclusion of HDL-C in risk-factor assessment , confirm the benefit of LDL-C reduction to a target goal , and suggest the need for re assessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention In the enrollment phase of the Air Force/Texas Coronary Atherosclerosis Prevention Study ( AFCAPS/TexCAPS ) , a number of heart disease-free potential subjects did not qualify to participate in the study because their low-density lipoprotein cholesterol ( LDL-C ) levels fluctuated . This report looks at the incidence of lability of LDL-C levels and premature coronary heart disease ( CHD ) in the nuclear family based on data collected on a group excluded primarily based on lipid levels during the enrollment phase at the TexCAPS site . Lipid inclusion criteria were total cholesterol ( TC ) , 180 mg/dL to 264 mg/dL ; low-density lipoprotein cholesterol ( LDL-C ) , 130 mg/dL to 190 mg/dL ; high-density lipoprotein cholesterol ( HDL-C ) , less than or equal to 45 mg/dL for men and less than or equal to 47 mg/dL for women ; and triglyceride ( TG ) concentrations , less than or equal to 400 mg/dL. After participants had been on the American Heart Association ( AHA ) step 1 diet for 8 to 10 weeks , lipid parameters were again tested in a total of 4257 individuals . Both lipid screening measurements at 8 and 10 weeks were required to be within 15 % of each other for inclusion in subsequent study . A total of 2868 individuals met the study criteria and were r and omly assigned to groups ; 1389 failed to qualify for a variety of reasons . Of these , 1070 ( 25.1 % of those who initially qualified based on lipid levels ) were excluded because of unacceptable lipid levels on the evaluations repeated at 8 and 10 weeks . This excluded sub population ( n = 1070 ) was stratified into three groups based on changes of LDL-C between 8 and 10 weeks on the AHA step 1 diet . One group had a less than 15 % fluctuation in LDL-C ( LN group , n = 637 , 15.0 % of cohort , n = 4257 ) . Of those with LDL-C variability , 177 had a greater than 15 % increase in LDL-C ( LI group , n = 177 , 4.2 % of cohort ) ; and 256 had a greater than 15 % decrease in LDL-C ( LD , n = 256 , 6.0 % of cohort ) . At week 8 , TC and LDL-C levels were lower and the HDL-C level was higher in the LN group compared with both groups having labile lipid levels ( LI and LD groups ) . Changes by gender showed similar trends ; however , HDL-C was 5 mg/dL lower at 8 weeks in both groups of women with labile LDL-C levels ( groups LI and LD ) when compared with the women in the LN group ( P < .01 ) . The frequency of TG concentrations greater than 150 mg/dL was greater in men having labile LDL-C level when compared with the control group . The trend was similar for women . In assessing the incidence of CHD in the nuclear family , parents of prob and s with labile LDL-C levels ( LI and LD groups ) had a higher frequency ( P = .0044 ) of premature CHD than parents of prob and s with stable LDL-C ( LN ) . The following conclusions can be drawn : ( 1 ) within the general population , there is a substantial number ( 10 % , 433 of 4257 ) of individuals with labile LDL-C levels ; ( 2 ) labile LDL-C levels in the prob and s were found to be associated with an increased familial frequency of premature CHD in their parents . Definition of the molecular basis for this lability of LDL-C could reveal new opportunities to regulate plasma cholesterol levels and thus have an impact on CHD-associated morbidity and mortality in a substantial portion of the general population BACKGROUND Patients with diabetes mellitus ( DM ) have a marked increase in coronary heart disease ( CHD ) events relative to those without DM . In a previous report from the Sc and inavian Simvastatin Survival Study using a clinical case definition of DM ( n = 202 ) , simvastatin-treated patients had significantly fewer CHD events compared with placebo-treated control subjects . OBJECTIVE To examine the effect of simvastatin therapy on CHD in patients with DM and impaired fasting glucose levels . METHODS Using the 1997 American Diabetes Association diagnostic criteria , we assessed the effect of simvastatin therapy post hoc for an average of 5.4 years in Sc and inavian Simvastatin Survival Study patients with normal fasting glucose ( n = 3237 ) , impaired fasting glucose ( n = 678 ) , and DM ( n = 483 ) . RESULTS Simvastatin-treated patients with DM had significantly reduced numbers of major coronary events ( relative risk [ RR ] = 0.58 ; P = .001 ) and revascularizations ( RR = 0.52 ; P = .005 ) . Total ( RR = 0.79 ; P = .34 ) and coronary ( RR = 0.72 ; P = .26 ) mortality were also reduced in DM , but not significantly , due to small sample size . In impaired fasting glucose ( IFG ) subjects , simvastatin use significantly reduced the number of major coronary events ( RR = 0.62 ; P = .003 ) , revascularizations ( RR = 0.57 ; P = .009 ) , and total ( RR = 0.57 ; P = .02 ) and coronary ( RR = 0.45 ; P = .007 ) mortality . CONCLUSION Our results extend previous findings in patients with DM to a larger cohort , confirming the benefit of cholesterol lowering with simvastatin treatment on CHD events . In addition , significant decreases in total mortality , major coronary events , and revascularizations were observed in simvastatin-treated patients with impaired fasting glucose levels . These results strongly support the concept that cholesterol lowering with simvastatin therapy improves the prognosis of patients with elevated fasting glucose levels ( > or = 6.0 mmol/L [ > or = 110 mg/ dL ] ) or DM and known CHD Limited data suggest that HMG-CoA reductase inhibitors ( statins ) may slow loss of renal function in individuals with chronic renal insufficiency . This study was conducted to determine whether pravastatin reduced rates of loss of renal function in people with moderate chronic renal insufficiency . This was a post hoc subgroup analysis of a r and omized double-blind placebo controlled trial . Data were analyzed from the CARE study ( a r and omized trial of pravastatin versus placebo in 4159 participants with previous myocardial infa rct ion and total plasma cholesterol < 240 mg/dl ) . Participants with estimated GFR ( MDRD-GFR ) < 60 ml/min per 1.73 m(2 ) body surface area at baseline were considered to have moderate chronic renal insufficiency . Multivariate regression was used to calculate rates of decline in MDRD-GFR for individuals receiving pravastatin and placebo , controlling for prospect ively determined covariates that might influence rates of renal function loss . Change in renal function could be calculated in 3384 individuals , of whom 690 ( 20.4 % ) had MDRD-GFR < 60 ml/min per 1.73 m(2 ) and were eligible for inclusion . Among all individuals with MDRD-GFR < 60 ml/min per 1.73 m(2 ) ) , the MDRD-GFR decline in the pravastatin group was not significantly different from that in the placebo group ( 0.1 ml/min per 1.73 m(2)/yr slower ; 95 % CI , -0.2 to 0.4 ; P = 0.49 ) . However , there was a significant stepwise inverse relation between MDRD-GFR before treatment and slowing of renal function loss with pravastatin use , with more benefit in those with lower MDRD-GFR at baseline ( P = 0.04 ) . Rate of change in MDRD-GFR in the pravastatin group was 0.6 ml/min per 1.73 m(2)/yr slower than placebo ( 95 % CI , -0.1 to 1.2 ; P = 0.07 ) in those with MDRD-GFR < 50 ml/min , and 2.5 ml/min per 1.73 m(2)/yr slower ( 95 % CI , 1.4 to 3.6 slower ; P = 0.0001 ) in those with MDRD-GFR < 40 ml/min per 1.73 m(2)/yr . Pravastatin also reduced rates of renal loss to a greater extent in participants with than without proteinuria at baseline ( P = 0.006 ) . It is concluded that pravastatin may slow renal function loss in individuals with moderate to severe kidney disease , especially those with proteinuria . These findings require confirmation by a large r and omized trial conducted specifically in people with chronic renal insufficiency Aims /hypothesisWe estimated the cost-effectiveness of atorvastatin treatment in the primary prevention of cardiovascular disease in patients with type 2 diabetes using data from the Collaborative Atorvastatin Diabetes Study (CARDS).Subjects and methods A total of 2,838 patients , who were aged 40 to 75 years and had type 2 diabetes without a documented history of cardiovascular disease and without elevated LDL-cholesterol , were recruited from 32 centres in the UK and Irel and and r and omly allocated to atorvastatin 10 mg daily ( n = 1,428 ) or placebo ( n = 1,410 ) . These subjects were followed-up for a median period of 3.9 years . Direct treatment costs and effectiveness were analysed to provide estimates of cost per endpoint-free year over the trial period for alternative definitions of endpoint , and of cost per life-year gained and cost per quality -adjusted life-year ( QALY ) gained over a patient ’s lifetime . Results Over the trial period , the incremental cost-effectiveness ratio ( ICER ) was estimated to be £ 7,608 per year free of any CARDS primary endpoint ; the ICER was calculated to be £ 4,896 per year free of any cardiovascular endpoint and £ 4,120 per year free of any study endpoint . Over lifetime , the incremental cost per life-year gained was £ 5,107 and the cost per QALY was £ 6,471 ( costs and benefits both discounted at 3.5 % ) . Conclusions /interpretation Primary prevention of cardiovascular disease with atorvastatin is a cost-effective intervention in patients with type 2 diabetes , with the ICER for this intervention falling within the current acceptance threshold ( £ 20,000 per QALY ) specified by the National Institute for Health and Clinical Excellence ( NICE ) The Air Force/Texas Coronary Atherosclerosis Prevention Study ( AFCAPS/TexCAPS ) is the first coronary heart disease ( CHD ) primary prevention trial of the cholesterol-reducing agents called " statins " to include women . For 5608 men and 997 postmenopausal women without clinical evidence of cardiovascular disease ( CVD ) who had average low-density lipoprotein cholesterol ( LDL-C ) and below average high-density lipoprotein cholesterol ( HDL-C ) , 20 - 40 mg/day lovastatin reduced first acute major coronary events ( AMCEs ) 37 % ( for those receiving placebo and lovastatin , respectively , 183 and 116 first AMCEs defined as fatal or nonfatal myocardial infa rct ion [ MI ] , unstable angina , or sudden cardiac death ; relative risk [ RR ] 0.63 ; 95 % confidence interval [ 95 % CI ] 0.50 , 0.79 ; p < 0.001 ) . Statistically significant reductions in prespecified secondary end points ( coronary revascularizations , unstable angina , MI , cardiovascular end point events , and coronary end point events ) were also associated with lovastatin treatment in the overall cohort . This paper provides results in women , a prespecified subgroup . Among women , 20 - 40 mg/day lovastatin reduced LDL-C 25 % and increased HDLC 9 % ( p < 0.001 ) . A prespecified analysis revealed consistency with the overall results regardless of gender ( i.e. , there were no statistical differences between men and women in risk reduction for first AMCEs with lovastatin ) . However , the number of women who had an AMCE was small , and there was insufficient power to detect a treatment group difference among women ( 7 of 499 vs. 13 of 498 first AMCEs in those receiving lovastatin and placebo , respectively ; RR 0.54 ; 95 % CI 0.22 , 1.35 ; p = 0.183 ) . Numerical reductions in all prespecified secondary end points were observed for women treated with lovastatin , but again , the numbers of events were small and the differences were not statistically significant . Chronic long-term treatment with lovastatin was well tolerated , with no treatment group differences in the frequency of cancer , muscle symptoms , and clinical ly important liver enzyme elevations . In AFCAPS/TexCAPS , a consistent pattern of numerical reductions in all prespecified primary and secondary cardiovascular end points was observed in women treated with lovastatin for primary prevention of CHD . However , because of the small number of events , there was insufficient power to detect significant treatment group differences . Lovastatin treatment was associated with statistically significant decreases in LDL-C and increases in HDL-C , and chronic long-term treatment with 20 - 40 mg/day lovastatin was well tolerated in women OBJECTIVES The Heart Protection Study ( HPS ) provides an opportunity to assess directly the effects of cholesterol-lowering therapy on major vascular events ( defined as myocardial infa rct ion , coronary death , stroke , or revascularization ) in patients with peripheral arterial disease ( PAD ) . In addition , the effects on peripheral vascular events ( ie , non-coronary revascularization , aneurysm repairs , major amputations or PAD deaths ) can be assessed . METHODS 6748 UK adults with PAD and 13,788 other high-risk participants were r and omly allocated to receive 40 mg simvastatin daily or matching placebo , yielding an average LDL cholesterol difference of 1.0 mmol/L ( 39 mg/dL ) during a mean of 5 years . RESULTS For participants with PAD , allocation to simvastatin was associated with a highly significant 22 % ( 95 % CI 15 - 29 ) relative reduction in the rate of first major vascular event following r and omisation ( 895 [ 26.4 % ] simvastatin-allocated vs 1101 [ 32.7 % ] placebo-allocated ; P < .0001 ) , which was similar to that seen among the other high-risk participants . The absolute reduction in first major vascular event was 63 ( SE 11 ) per 1000 patients with PAD and 50 ( SE 7 ) per 1000 without pre-existing PAD . Overall , among all participants , there was a 16 % ( 5 - 25 ) relative reduction in the rate of first peripheral vascular event following r and omisation ( 479 [ 4.7 % ] simvastatin vs 561 [ 5.5 % ] placebo ) , largely irrespective of baseline LDL cholesterol and other factors . This effect chiefly reflects a 20 % ( 8 - 31 ) relative reduction in non-coronary revascularization procedures ( 334 [ 3.3 % ] vs 415 [ 4.0 % ] ; P = .002 ) . CONCLUSION HPS demonstrates the benefits of cholesterol-lowering statin therapy in patients with PAD , regardless of their presenting cholesterol levels and other presenting features . Allocation to 40 mg simvastatin daily reduces the rate of first major vascular events by about one-quarter , and that of peripheral vascular events by about one-sixth , with large absolute benefits seen in participants with PAD because of their high vascular risk . Consequently , statin therapy should be considered routinely for all patients with PAD OBJECTIVES This study sought to determine if an aggressive , focused low-density lipoprotein cholesterol (LDL-C)-lowering strategy was superior to usual care for coronary heart disease ( CHD ) patients enrolled in health maintenance organization or Veterans Administration setting s. BACKGROUND Statin therapy benefits are well established . No prospect i ve , r and omized studies have tested strategies to optimize these benefits in a " real-world " setting . METHODS A total of 2,442 CHD patients with hyperlipidemia were r and omized to either an aggressive treatment arm using atorvastatin or usual care and followed for 51.5 months on average . Atorvastatin-group patients were titrated to LDL-C goals of < 80 mg/dl ( 2.1 mmol/l ) or a maximum atorvastatin dose of 80 mg/day . Usual-care patients received any treatment deemed appropriate by their regular physicians . End point assessment s were complete in 958 atorvastatin-group and 941 usual-care patients . Partial assessment s occurred in 259 patients in the atorvastatin group and 284 patients in the usual care group who did not complete four years of study participation because of adverse events , withdrawn consent , or follow-up loss . The primary efficacy parameter was time to first cardiovascular event . RESULTS A total of 289 ( 23.7 % ) patients in the atorvastatin group compared with 333 ( 27.7 % ) patients in the usual care group experienced a primary outcome ( hazard ratio , 0.83 ; 95 % confidence interval 0.71 to 0.97 , p = 0.02 ) . This reduction in morbidity was largely due to fewer non-fatal myocardial infa rct ions ( 4.3 % vs. 7.7 % , p = 0.0002 ) . Levels of LDL-C were reduced more ( 34.3 % vs. 23.3 % , p < 0.0001 ) and National Cholesterol Education Program goals ( LDL-C < 100 mg/dl ) more likely met at end-of- study visits ( 72.4 % vs. 40.0 % ) in patients receiving atorvastatin compared with those receiving usual care . CONCLUSIONS An aggressive , focused statin therapy management strategy outperformed usual care in health maintenance organization and Veterans Administration clinic patients with CHD Although hyperlipidemia is associated with the development of diabetes complications , the effect of lipid reduction on microvascular complications is unknown . We initiated a 2-year , r and omized , double-blinded placebo-controlled pilot trial of simvastatin/diet vs. diet alone in Type 1 diabetic patients without overt nephropathy . Thirty-nine patients with LDL cholesterol 100 - 160 mg/dl , > 10 year duration of diabetes and an albumin excretion rate ( AER ) < 200 microg/min were recruited for study . The primary end-point was change in AER . Secondary end-points were change in ankle-brachial index , progression of retinopathy status , change in vibratory threshold , and development of new clinical neuropathy . Nineteen patients were treated with simvastatin and twenty with placebo . However , because of the lowering of drug initiation levels by the American Diabetes Association , the trial was terminated early with 2 subjects reaching 2 years , 17 reaching 18 months , 36 reaching 1 year , and all 6 months . Simvastatin significantly reduced total cholesterol ( mean on treatment 173.4 vs. 191.4 , P=.020 ) and LDL cholesterol ( mean on treatment 105.0 vs. 127.7 , P<.001 ) . Simvastatin therapy was associated with a slower rise in AER compared to placebo , though the result was not statistically significant ( median rate of change/month 0.004 vs. 0.029 ) . There was a trend towards slower progression of neuropathy as measured by vibratory threshold ( median change at 1 year 0.03 simvastatin vs. 0.94 , P=.07 ) . There was no difference in change in ankle-brachial index , clinical neuropathy status , or retinopathy status . In conclusion , treatment with simvastatin may have a beneficial effect on early nephropathy and diabetic neuropathy , justifying a fully powered trial . However , this would be difficult under current treatment guidelines High-dose statin therapy has been demonstrated to provide incremental benefit when low-density lipoprotein ( LDL ) cholesterol concentrations are lowered well below recommended target levels . This secondary analysis of the Treating to New Targets ( TNT ) study was conducted to investigate whether the attainment of very low LDL cholesterol levels was associated with a further reduction in major cardiovascular events compared with higher LDL cholesterol concentrations and whether any incremental benefit was achieved without additional safety risk . Patients with coronary heart disease and LDL cholesterol levels < 130 mg/dl ( 3.4 mmol/L ) were r and omized to therapy with atorvastatin 10 mg/day ( n = 5,006 ) or 80 mg/day ( n = 4,995 ) . The primary end point was the occurrence of a first major cardiovascular event . Clinical outcomes and safety data were compared across on-treatment LDL cholesterol quintiles . There was a highly significant reduction in the rate of major cardiovascular events with descending achieved levels of on-treatment LDL cholesterol ( p < 0.0001 for trend across LDL cholesterol ) . Analysis of individual components of the primary end point demonstrated similar results . Death from any cause and from noncardiovascular causes was lowest in patients with the lowest on-treatment LDL cholesterol levels . Cardiovascular deaths were also reduced with lower levels of on-treatment LDL cholesterol . There were no clinical ly important differences in adverse event rates across quintiles . Specifically , no increase in muscle complaints , suicide , hemorrhagic stroke , or cancer deaths was observed at the lowest LDL cholesterol levels . In conclusion , the present analysis adds support to the concept that for patients with established atherosclerotic cardiovascular disease , a further risk reduction without sacrifice of safety can be achieved by reducing LDL cholesterol to very low levels BACKGROUND A potentially modifiable risk factor for cardiovascular disease in patients with mild chronic renal insufficiency is dyslipidemia . Few studies examined the effects of statins on all-cause mortality and major coronary events in patients with renal dysfunction . METHODS We performed a post hoc analysis from the R and omized Trial of Cholesterol Lowering in 4,444 Patients with Coronary Heart Disease : The Sc and inavian Simvastatin Survival Study . Of 4,444 participants , 2,314 ( 52.1 % ) had mild chronic renal insufficiency defined as an estimated glomerular filtration rate less than 75 mL/min/1.73 m(2 ) ( < 1.25 mL/s ) , measured using the Modification of Diet in Renal Disease equation . The primary end point was all-cause mortality . RESULTS During the follow-up period , simvastatin use was associated with decreased all-cause mortality ( adjusted hazard ratio [ HR ] , 0.69 ; confidence interval [ CI ] , 0.54 to 0.89 ) in the 2,314 participants with mild chronic renal insufficiency . Rates of major coronary events ( adjusted HR , 0.67 ; CI , 0.56 to 0.79 ) and coronary revascularization ( adjusted HR , 0.62 ; CI , 0.49 to 0.77 ) also were significantly lower in the simvastatin group . No significant decreases in stroke incidence were observed in the simvastatin group ( adjusted HR , 0.88 ; CI , 0.55 to 1.39 ) . The side-effect profile was similar between the 2 treatment groups . CONCLUSION Simvastatin therapy appears to be effective and safe for the secondary prevention of all-cause mortality and major coronary events in patients with mild chronic renal dysfunction BACKGROUND The presence of coexisting conditions has a substantial effect on the outcome of acute myocardial infa rct ion . Renal failure is associated with one of the highest risks , but the influence of milder degrees of renal impairment is less well defined . METHODS As part of the Valsartan in Acute Myocardial Infa rct ion Trial ( VALIANT ) , we identified 14,527 patients with acute myocardial infa rct ion complicated by clinical or radiologic signs of heart failure , left ventricular dysfunction , or both , and a documented serum creatinine measurement . Patients were r and omly assigned to receive captopril , valsartan , or both . The glomerular filtration rate ( GFR ) was estimated by means of the four-component Modification of Diet in Renal Disease equation , and the patients were grouped according to their estimated GFR . We used a 70-c and i date variable model to adjust and compare overall mortality and composite cardiovascular events among four GFR groups . RESULTS The distribution of estimated GFR was wide and normally shaped , with a mean ( + /-SD ) value of 70+/-21 ml per minute per 1.73 m2 of body-surface area . The prevalence of coexisting risk factors , prior cardiovascular disease , and a Killip class of more than I was greatest among patients with a reduced estimated GFR ( less than 45.0 ml per minute per 1.73 m2 ) , and the use of aspirin , beta-blockers , statins , or coronary-revascularization procedures was lowest in this group . The risk of death or the composite end point of death from cardiovascular causes , reinfa rct ion , congestive heart failure , stroke , or resuscitation after cardiac arrest increased with declining estimated GFRs . Although the rate of renal events increased with declining estimated GFRs , the adverse outcomes were predominantly cardiovascular . Below 81.0 ml per minute per 1.73 m2 , each reduction of the estimated GFR by 10 units was associated with a hazard ratio for death and nonfatal cardiovascular outcomes of 1.10 ( 95 percent confidence interval , 1.08 to 1.12 ) , which was independent of the treatment assignment . CONCLUSIONS Even mild renal disease , as assessed by the estimated GFR , should be considered a major risk factor for cardiovascular complications after a myocardial infa rct ion OBJECTIVES We sought to assess the ability of N-terminal pro-B-type natriuretic peptide ( N-BNP ) to predict vascular events in high-risk people and to test whether statins benefit people with high levels of N-BNP . BACKGROUND The predictive value of N-BNP for occlusive vascular events and the effects of statins in people with high N-BNP levels are uncertain . METHODS A total of 20,536 people were assigned r and omly to simvastatin 40 mg daily or placebo for an average of 5 years . Five baseline N-BNP groups were defined ( < 386 ; 386 to 1,171 ; 1,172 to 2,617 ; 2,618 to 5,758 ; and > or = 5,759 pg/ml ) . RESULTS Baseline N-BNP was strongly predictive of future vascular events independently of other characteristics . Compared with participants with N-BNP < 386 pg/ml , those with levels > or = 5,759 pg/ml had adjusted relative risks for major vascular events ( MVEs ) ( i.e. , major coronary events [ MCE ] [ nonfatal myocardial infa rct ion or coronary death ] , stroke , or revascularization ) of 2.26 , for MCE of 3.09 , for stroke of 1.80 , and for heart failure ( hospitalization or death ) of 9.23 ( all p < 0.0001 ) . Overall , simvastatin allocation reduced the relative risk of MVE by 24 % ( 95 % confidence interval 19 to 28 ) . There was a trend toward smaller ( but still significant ) proportional reductions in MVE among participants with greater baseline N-BNP levels , but the absolute benefits of simvastatin allocation were similar at all N-BNP levels . Simvastatin allocation was also associated with a 14 % ( 95 % confidence interval 0 to 25 ) proportional reduction in heart failure . No excess risk of other vascular and nonvascular outcomes was observed with simvastatin allocation among participants with greater baseline values of N-BNP . CONCLUSIONS In this study , N-BNP levels were strongly predictive not only of heart failure but also of MVEs . In people with high N-BNP levels consistent with heart failure , statin allocation significantly reduced vascular risk , with no evidence of hazard . ( http://www.controlledtrials.com/IS RCT N48489393/48489393 ) AIM To assess differences in treatment of ischaemic heart disease in the Sc and inavian countries . METHODS AND RESULTS The Sc and inavian Simvastatin Survival Study ( 4S ) lasted 5.4 years and showed that death rates in 4444 patients with coronary heart disease were 30 % lower in those treated with simvastatin to lower serum cholesterol than in those given placebo . Apart from this main result , the 4S provided detailed information on rates of death and other manifestations of coronary heart disease , as well as on use of non-lipid forms of therapy . There were substantial differences in 4S placebo group rates of mortality , coronary deaths and major coronary events between countries . Surgical and medical therapy varied importantly between countries . CONCLUSIONS Major inter-country differences in rates of death and myocardial infa rct ion in patients with coronary heart disease were likely to be due to a composite of differences in baseline characteristics including smoking . They occurred in a setting of very uneven exploitation of the potential for improving survival of patients with ischaemic heart disease The Justification for the Use of statins in Primary prevention : an Intervention Trial Evaluating Rosuvastatin ( JUPITER ) is a r and omized , double-blind , placebo-controlled primary prevention trial of statin therapy among persons with average to low levels of low-density lipoprotein ( LDL ) cholesterol who are at increased cardiovascular risk due to elevated plasma concentrations of the inflammatory biomarker high-sensitivity C-reactive protein ( hs-CRP ) . A total of 17,802 persons with LDL cholesterol<130 mg/dl ( 3.36 mmol/L ) and hs-CRP > or=2 mg/L were recruited from 26 countries and r and omly allocated to 20 mg/day rosuvastatin or placebo . In contrast to previous studies of statin therapy in primary prevention , JUPITER is evaluating a group with modest plasma concentrations of LDL cholesterol ( median 108 mg/dl , interquartile range 94 to 119 ) . Further , the trial includes 6,801 women ( 38.2 % ) and 5,577 participants with metabolic syndrome ( 32.1 % ) . Thus , in addition to broadening our underst and ing of statin therapy and inflammation , the JUPITER trial will provide important and clinical ly relevant information on primary prevention among patients who do not currently qualify for lipid-lowering therapy . In conclusion , as 20 mg of rosuvastatin can reduce LDL cholesterol by up to 50 % , JUPITER will also provide crucial safety data for several thous and patients who should achieve LDL cholesterol levels<50 mg/dl on a long-term basis AIM In recent reports , some kinds of HMG-CoA reductase inhibitors were able to decrease proteinuria and to improve renal function . Here we aim ed to clarify the effect of fluvastatin ( an HMG-CoA reductase inhibitor ) on proteinuria and renal function in children with mild IgA nephropathy . PATIENTS AND METHODS We conducted a prospect i ve controlled study of 30 children who had been recently diagnosed with normocholesterolemic IgA nephropathy following the detection of a minor lesion or of focal mesangial proliferation and moderate proteinuria . The 30 patients were r and omly assigned to receive both of 20 mg of fluvastatin and 5 mg/kg of dipyridamole ( group 1 ) , or 5 mg/kg of dipyridamole only ( group 2 ) for 1 year . RESULTS By the end of the trial , urinary protein , hematuria , BUN and serum creatinine levels had significantly decreased in the patients of group 1 as compared to baseline . Serum total cholesterol , triglyceride and LDL cholesterol levels had significantly decreased , while serum total protein and albumin , and creatinine clearance had significantly increased in group 1 as compared to baseline and group 2 . The urinary protein level had significantly decreased in the group 2 patients as compared to baseline , but only slightly . CONCLUSIONS The results of this study suggest that fluvastatin and dipyridamole treatment yields an antiproteinuric effect and leads to the amelioration of renal function in moderately proteinuric patients with mild histological IgA nephropathy Experimental evidence suggests that lipid lowering therapy could slow the progression of renal disease in humans . We have conducted a double-blind , placebo controlled trial of the HMG CoA reductase inhibitor simvastatin in patients with the nephrotic syndrome or significant proteinuria ( > 1 g/day ) and hypercholesterolemia ( > or = 6.5 mmol/liter ) . Patients were placed on a lipid lowering diet for at least 10 weeks before r and omization . After a four-week placebo run-in , 30 adults were r and omized to simvastatin or placebo therapy ( 10 mg/day , increasing to 20 to 40 mg/day as required ) for 24 weeks . There were seven dropouts , none of whom were " definitely " related to drug therapy . Total and LDL cholesterol levels fell by a mean of 33 and 31 % , respectively , in simvastatin treated patients , compared with only 5 and 1 % in patients on placebo ( P < 0.001 , P = 0.002 , respectively ) . Apolipoprotein B100 levels fell by a mean of 31 % in the simvastatin group but rose 0.3 % in the placebo group ( P = 0.014 ) . There were no significant changes in HDL levels . There were no significant differences between the groups in their urine protein levels , their rise in plasma creatinine , or decline in plasma inulin clearance . Simvastatin is a safe , effective therapy for hypercholesterolemia in proteinuric states . A much larger trial is needed to show if potent lipid-lowering therapy slows progression of hypercholesterolemic proteinuric diseases BACKGROUND Dyslipidemia is common in patients with chronic kidney disease . The role of statin therapy in the progression of kidney disease is unclear . STUDY DESIGN Prospect i ve r and omized clinical trial , post hoc analyses . SETTING & PARTICIPANTS 10,060 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( lipid-lowering component ) stratified by baseline estimated glomerular filtration rate ( eGFR ) : less than 60 , 60 to 89 , and 90 or greater mL/min/1.73 m(2 ) . Mean follow-up was 4.8 years . INTERVENTION R and omized ; pravastatin , 40 mg/d , or usual care . OUTCOMES & MEASUREMENTS Total , high-density lipoprotein , and low-density lipoprotein cholesterol ; end-stage renal disease ( ESRD ) , eGFR . RESULTS Through year 6 , total cholesterol levels decreased in the pravastatin ( -20.7 % ) and usual-care groups ( -11.2 % ) . No significant differences were seen between groups for rates of ESRD ( 1.36 v 1.45/100 patient-years ; P = 0.9 ) , composite end points of ESRD and 50 % or 25 % decrease in eGFR , or rate of change in eGFR . Findings were consistent across eGFR strata . In patients with eGFR of 90 mL/min/1.73 m(2 ) or greater , the pravastatin arm tended to have a higher eGFR . LIMITATIONS Proteinuria data unavailable , post hoc analyses , unconfirmed validity of the Modification of Diet in Renal Disease Study equation in normal eGFR range , statin drop-in rate in usual-care group with small cholesterol differential between groups . CONCLUSIONS In hypertensive patients with moderate dyslipidemia and decreased eGFR , pravastatin was not superior to usual care in preventing clinical renal outcomes . This was consistent across the strata of baseline eGFR . However , benefit from statin therapy may depend on the degree of the cholesterol level decrease achieved Statins improve cardiovascular survival in both nondiabetic and diabetic patients , but diabetic patients benefit more , in both primary and secondary prevention . Statins seem to have multiple effects beyond cholesterol lowering , that is , pleiotropic effects that may include changes in renal function . This study tests the hypothesis that acute treatment with atorvastatin may change glomerular filtration rate , tubular function , vasoactive hormones , blood pressure , and pulse rate in patients with type 2 diabetes . In an acute , r and omized , placebo-controlled , double-blinded , crossover trial , the effects of atorvastatin on renal function , vasoactive hormones , blood pressure , and pulse rate are measured in 21 patients with type 2 diabetes . Patients are r and omized to either 2 doses of atorvastatin 80 mg or placebo before 2 different study days . Treatment with atorvastatin induces a significant reduction in fractional sodium excretion compared with placebo , and sodium clearance tends to be reduced . No significant differences in glomerular filtration rate , albumin/creatinine ratio , vasoactive hormones , and blood pressure by acute treatment with atorvastatin are found in diabetic patients . Acute treatment with atorvastatin reduces renal fractional sodium excretion in patients with type 2 diabetes . No changes are measured in glomerular filtration rate , albumin/creatinine ratio , vasoactive hormones , and blood pressure Aims /hypothesis . The purpose of this study is to investigate the cost-effectiveness of simvastatin in diabetic patients , using prospect ively collected outcomes data from the Sc and inavian Simvastatin Survival Study . Methods . Diabetic patients were identified using two different classifications schemes : Clinical history ( diabetic , non-diabetic ) and the new American Diabetes Association definition ( diabetic , impaired fasting glucose , normal fasting glucose ) . The analysis is based on prospect ively collected data from the trial on hospitalization for cardiovascular problems , study drug utilization and mortality . The incremental cost per life year saved with simvastatin is estimated using costs from Sweden ( primary ) and other European countries . Results . Hospitalizations for cardiovascular problems were considerably reduced with simvastatin therapy , with the greatest differences in the diabetic subgroups . Reductions in hospitalizations in the diabetic group result ed in substantial hospital cost savings that offset 67 to 76 % of the drug cost ( depending on the classification used ) . For the diabetic patients , the estimates of the cost per life-year gained ranged from 1600 Euros ( based on clinical history ) to 3200 Euros ( based on American Diabetes Association ) using Swedish costs . In the other evaluated European countries treatment with simvastatin showed a favourable cost-effectiveness ratio independent of differences in local health care unit costs . Conclusion /interpretation . For all subgroups in the diabetic classification schemes , treatment with simvastatin result ed in estimates of cost per life-year gained that were well within the range generally considered to be cost effective . Based on the Sc and inavian Simvastatin Survival Study , simvastatin therapy provides good value for money in both diabetic and non-diabetic patients with cardiovascular disease . [ Diabetologia ( 1999 ) 42 : 1293–1301 BACKGROUND The endogenous inhibitor of nitric oxide ( NO ) synthase , asymmetric dimethylarginine ( ADMA ) , is a strong cardiovascular ( CV ) risk marker in patients with chronic renal insufficiency . Statins have pleiotropic effects and are currently considered as potential ADMA-lowering agents . METHODS We investigated the effect of simvastatin on plasma ADMA levels in 35 patients with chronic kidney disease ( CKD ) by performing a secondary analysis of a r and omized double-blind placebo-controlled trial where patients were r and omized to receive simvastatin or placebo for 6 months . RESULTS Plasma ADMA was higher in CKD patients ( 0.84 + /- 0.14 micromol/L ) than in healthy subjects ( 0.69 + /- 0.10 micromol/L ) ( p<0.001 ) . In CKD patients , ADMA at baseline was related directly with triglycerides ( r=0.42 , p=0.01 ) and inversely with HDL cholesterol ( r=-0.37 , p=0.03 ) and creatinine clearance ( p=0.03 ) . As expected , simvastatin caused significant reductions in total cholesterol , LDL cholesterol and triglycerides , as well as in C-reactive protein ( CRP ; -28 % , p=0.001 ) and IL-6 ( -20 % , p=0.05 ) but failed to decrease plasma ADMA both in crude and adjusted analyses . CONCLUSIONS Simvastatin does not modify plasma ADMA . Because raised ADMA is known to prevent the favorable effect of statins on myocardial blood flow , co interventions aim ed at lowering or antagonizing ADMA may either prompt or potentiate the cardiovascular protective effect of simvastatin BACKGROUND Patients with chronic kidney disease are at increased risk for cardiovascular disease , but the efficacy and safety of simvastatin and aspirin are unknown in this patient group . METHODS Patients were r and omly assigned in a 2 x 2 factorial design to the administration of : ( 1 ) 20 mg of simvastatin daily versus matching placebo , and ( 2 ) 100 mg of modified-release aspirin daily versus matching placebo . RESULTS Overall , 448 patients with chronic kidney disease were r and omly assigned ( 242 predialysis patients with a creatinine level > or = 1.7 mg/dL [ > or = 150 micromol/L ] , 73 patients on dialysis therapy , and 133 patients with a functioning transplant ) . Compliance with study treatments was 80 % at 12 months . Allocation to treatment with 100 mg of aspirin daily was not associated with an excess of major bleeds ( aspirin , 4 of 225 patients [ 2 % ] versus placebo , 6 of 223 patients [ 3 % ] ; P = not significant [ NS ] ) , although there was a 3-fold excess of minor bleeds ( 34 of 225 [ 15 % ] versus 12 of 223 patients [ 5 % ] ; P = 0.001 ) . Among those with predialysis renal failure or a functioning transplant at baseline , aspirin did not increase the number of patients who progressed to dialysis therapy ( 7 of 187 [ 4 % ] versus 6 of 188 patients [ 3 % ] ; P = NS ) or experienced a greater than 20 % increase in creatinine level ( 63 of 187 patients [ 34 % ] versus 56 of 188 patients [ 30 % ] ; P = NS ) . After 12 months of follow-up , allocation to 20 mg of simvastatin daily reduced nonfasting total cholesterol levels by 18 % ( simvastatin , 163 mg/dL [ 4.22 mmol/L ] versus placebo , 196 mg/dL [ 5.08 mmol/L ] ; P < 0.0001 ) , directly measured low-density lipoprotein cholesterol levels by 24 % ( 89 mg/dL [ 2.31 mmol/L ] versus 114 mg/dL [ 2.96 mmol/L ] ; P < 0.0001 ) , and triglyceride levels by 13 % ( 166 mg/dL [ 1.87 mmol/L ] versus 186 mg/dL [ 2.10 mmol/L ] ; P < 0.01 ) , but there was no significant effect on high-density lipoprotein cholesterol levels ( 2 % increase ; P = NS ) . Allocation to simvastatin therapy was not associated with excess risk for abnormal liver function test results or elevated creatine kinase levels . CONCLUSION During a 1-year treatment period , simvastatin , 20 mg/d , produced a sustained reduction of approximately one quarter in low-density lipoprotein cholesterol levels , with no evidence of toxicity , and aspirin , 100 mg/d , did not substantially increase the risk for a major bleeding episode . Much larger trials are now needed to assess whether these treatments can prevent vascular events OBJECTIVE To investigate the effect of intensive lipid lowering with high-dose atorvastatin on the incidence of major cardiovascular events compared with low-dose atorvastatin in patients with coronary artery disease and type 2 diabetes , with and without chronic kidney disease ( CKD ) . PATIENTS AND METHODS Following 8 weeks ' open-label therapy with atorvastatin ( 10 mg/d ) , 10,001 patients with coronary artery disease were r and omized to receive double-blind therapy with either 80 mg/d or 10 mg/d of atorvastatin between July 1 , 1998 , and December 31 , 1999 . Of 1501 patients with diabetes , renal data were available for 1431 . Patients with CKD were defined as having a baseline estimated glomerular filtration rate ( eGFR ) below 60 mL/min per 1.73 m2 , using the Modification of Diet in Renal Disease equation . RESULTS After a median follow-up of 4.8 years , 95 ( 17.4 % ) of 546 patients with diabetes and CKD experienced a major cardiovascular event vs 119 ( 13.4 % ) of 885 patients with diabetes and normal eGFRs ( hazard ratio [ HR ] , 1.32 ; 95 % confidence interval [ CI ] , 1.00 - 1.72 ; P<.05 ) . Compared with 10 mg of atorvastatin , 80 mg of atorvastatin reduced the relative risk of major cardiovascular events by 35 % in patients with diabetes and CKD ( 20.9 % [ 57/273 ] vs 13.9 % [ 38/273 ] ; HR , 0.65 ; 95 % CI , 0.43 - 0.98 ; P=.04 ) and by 10 % in patients with diabetes and normal eGFR ( 14.1 % [ 62/441 ] vs 12.8 % [ 57/444 ] ; HR , 0.90 ; 95 % CI , 0.63 - 1.29 ; P=.56 ) . The absolute risk reduction in patients with diabetes and CKD was substantial , yielding a number needed to treat of 14 to prevent 1 major cardiovascular event over 4.8 years . Both treatments were well tolerated . CONCLUSION Patients with diabetes , stable coronary artery disease , and mild to moderate CKD experience marked reduction in cardiovascular events with intensive lipid lowering , in contrast to previous observations in patients with diabetes and end-stage renal disease . TRIAL REGISTRATION clinical trials.gov identifier : NCT00327691 BACKGROUND In type 2 diabetes mellitus the aetiology of long-term complications is multifactorial . We carried out a r and omised trial of stepwise intensive treatment or st and ard treatment of risk factors in patients with microalbuminuria . METHODS In this open , parallel trial patients were allocated st and ard treatment ( n=80 ) or intensive treatment ( n=80 ) . St and ard treatment followed Danish guidelines . Intensive treatment was a stepwise implementation of behaviour modification , pharmacological therapy targeting hyperglycaemia , hypertension , dyslipidaemia , and microalbuminuria . The primary endpoint was the development of nephropathy ( median albumin excretion rate > 300 mg per 24 h in at least one of the two-yearly examinations ) . Secondary endpoints were the incidence or progression of diabetic retinopathy and neuropathy . FINDINGS The mean age was 55.1 years ( SD 7.2 ) and patients were followed up for 3.8 years ( 0.3 ) . Patients in the intensive group had significantly lower rates of progression to nephropathy ( odds ratio 0.27 [ 95 % CI 0 - 10 - 0.75 ] ) , progression of retinopathy ( 0.45 [ 0.21 - 0.95 ] ) , and progression of autonomic neuropathy ( 0.32 [ 0.12 - 0.78 ] ) than those in the st and ard group . INTERPRETATION Intensified multifactorial intervention in patients with type 2 diabetes and microalbuminuria slows progression to nephropathy , and progression of retinopathy and autonomic neuropathy . However , further studies are needed to establish the effect of intensified multifactorial treatment on macrovascular complications and mortality This study describes the rationale , design , and baseline characteristics of a trial to determine whether treatment with fosinopril 20 mg/day and /or pravastatin 40 mg/ day will prevent cardiovascular and renal disease in nonhypertensive ( RR < 160/100 mm Hg and not using antihypertensive medication ) and nonhypercholesterolemic ( total cholesterol < 8.0 or < 5.0 mmol/L in case of previous myocardial infa rct ion and not using lipid lowering medication ) men and women with persistent microalbuminuria ( urinary albumin excretion > 10 mg/L once in an early morning spot urine and 15 to 300 mg/24-hour at least once in two 24-hour urine collection s ) . The Prevention of REnal and Vascular ENdstage Disease Intervention Trial is a single-center , double-blind , r and omized , placebo-controlled trial with a 2 x 2 factorial design . The 864 r and omized subjects will be monitored for a minimum of 4 years and a maximum of 5 years . The primary efficacy parameter is defined as the combined incidence of all-cause mortality or hospital admission for documented ( 1 ) nonfatal myocardial infa rct ion , ( 2 ) myocardial ischemia , ( 3 ) heart failure , ( 4 ) peripheral vascular disease , ( 5 ) cerebrovascular accident and /or ( 6 ) end-stage renal disease Background / Aims : To determine whether cerivastatin , a newly developed novel synthetic potent statin , exerts a renoprotective effect , we assessed urinary albumin excretion ( UAE ) and plasma and urinary endothelin (ET)-1 concentrations in normotensive microalbuminuric type 2 diabetes patients with dyslipidemia . Methods : Sixty normotensive type 2 diabetic patients ( 38 men and 22 women ; mean age 56.5 years ) with microalbuminuria ( 20–200 µg/min ) and dyslipidemia ( total cholesterol > 200 mg/dl , LDL cholesterol > 160 mg/dl , HDL cholesterol < 35 mg/dl , and triglyceride > 150 mg/dl ) were enrolled in a double-blind study for 6 months , receiving either cerivastatin ( 0.15 mg/day ) or placebo . Plasma and urinary ET-1 concentrations were measured by radioimmunoassay . Results : Cerivastatin did not affect serum creatinine and HbA1c levels , and reduced systolic blood pressure slightly , but not significantly . Plasma levels of total cholesterol and LDL cholesterol were significantly reduced ( p < 0.01 ) , and plasma triglyceride levels were also reduced significantly ( p < 0.05 ) after 6 months of cerivastatin treatment . A concomitant significant decrease in UAE ( p < 0.01 ) , and urinary and plasma ET-1 concentrations ( p < 0.01 ) were found during this period . Conclusion : The use of cerivastatin is associated with decreased microalbuminuria and plasma and urinary ET-1 levels in microalbuminuric patients with type 2 diabetic mellitus and speculate that this may represent an amelioration of renal injury OBJECTIVES To investigate the relation between chronic kidney disease ( CKD ) and cardiovascular disease ( CVD ) and retrospectively to evaluate the effect of low dose of pravastatin in Japanese hypercholesterolemic patients with CKD enrolled in the large-scale r and omized MEGA Study . METHODS In this post hoc analysis , effect of low dose pravastatin treatment ( 10 - 20 mg daily ) on the primary prevention of the cardiovascular disease and renal function after 5 years was evaluated in 7196 patients with normal kidney function/mild CKD or moderate CKD . Patients were classified based on an estimated glomerular filtration rate ( eGFR ) > or=60 or 30-<60mL/min/1.73m(2 ) as having normal renal function/mild CKD or moderate CKD , respectively . Since Japanese guidelines do not allow statin use in patients with severe kidney disease , such individuals were excluded . RESULTS The incidence of CVD events was 35 - 49 % higher in patients with moderate CKD than in those with normal renal function/mild CKD . Notably , in the moderate CKD group pravastatin significantly reduced CHD by 48 % ( P=0.02 ) , stroke by 73 % ( P<0.01 ) , CVD by 55 % ( P<0.01 ) , and total mortality by 51 % ( P=0.02 ) . Moreover , the change in eGFR during follow-up in patients with moderate CKD was significantly ( P=0.03 ) higher in those assigned to receive diet plus pravastatin ( + 6.3 % ) compared with those on diet alone ( + 5.1 % ) . CONCLUSIONS Risk of CVD is higher in patients with moderate CKD compared with those with normal renal function/mild CKD , and was significantly reduced by treatment with pravastatin . Pravastatin also exerted beneficial effects on renal function in patients with moderate CKD Background and hypothesis : The predictive value of specific markers of infection and autoimmunity for coronary events , such as the effects of statins on inflammation , is still controversial . CONTEXT Previous studies indicate that the interpretation of trial results can be distorted by authors of published reports . OBJECTIVE To identify the nature and frequency of distorted presentation or " spin " ( ie , specific reporting strategies , whatever their motive , to highlight that the experimental treatment is beneficial , despite a statistically nonsignificant difference for the primary outcome , or to distract the reader from statistically nonsignificant results ) in published reports of r and omized controlled trials ( RCTs ) with statistically nonsignificant results for primary outcomes . DATA SOURCES March 2007 search of MEDLINE via PubMed using the Cochrane Highly Sensitive Search Strategy to identify reports of RCTs published in December 2006 . STUDY SELECTION Articles were included if they were parallel-group RCTs with a clearly identified primary outcome showing statistically nonsignificant results ( ie , P > or = .05 ) . DATA EXTRACTION Two readers appraised each selected article using a pretested , st and ardized data abstract ion form developed in a pilot test . RESULTS From the 616 published reports of RCTs examined , 72 were eligible and appraised . The title was reported with spin in 13 articles ( 18.0 % ; 95 % confidence interval [ CI ] , 10.0%-28.9 % ) . Spin was identified in the Results and Conclusions sections of the abstract s of 27 ( 37.5 % ; 95 % CI , 26.4%-49.7 % ) and 42 ( 58.3 % ; 95 % CI , 46.1%-69.8 % ) reports , respectively , with the conclusions of 17 ( 23.6 % ; 95 % CI , 14.4%-35.1 % ) focusing only on treatment effectiveness . Spin was identified in the main-text Results , Discussion , and Conclusions sections of 21 ( 29.2 % ; 95 % CI , 19.0%-41.1 % ) , 31 ( 43.1 % ; 95 % CI , 31.4%-55.3 % ) , and 36 ( 50.0 % ; 95 % CI , 38.0%-62.0 % ) reports , respectively . More than 40 % of the reports had spin in at least 2 of these sections in the main text . CONCLUSION In this representative sample of RCTs published in 2006 with statistically nonsignificant primary outcomes , the reporting and interpretation of findings was frequently inconsistent with the results Context What is the optimal monitoring interval for patients taking cholesterol-lowering medication ? Contribution This analysis of data from a trial that compared pravastatin with placebo in patients with coronary disease found that the signalnoise ratio in cholesterol monitoring was weak . Short-term variability of measurement was about 0.80 to 0.80 mmol/L ( 31 to 31 mg/dL ) . Calculations suggested that frequent follow-up of patients with values 0.5 mmol/L ( 19 mg/dL ) or more under target detected many more false-positive results than truly elevated cholesterol values . Implication Consider testing adherent patients with well-controlled cholesterol levels every 3 to 5 years rather than every few months or annually . The Editors Cholesterol level monitoring is a common clinical activity . Because indications for treatment have been widening over the past decade , cholesterol-lowering medications have become some of the most widely used and expensive pharmaceutical items , and cholesterol screening , treatment , and monitoring have increased . For example , lipid panels were the third highest contributors to Medicare testing growth between 2000 and 2004 , with a 61 % increase in volume and a 65 % increase in cost ( 1 ) . Previous studies have suggested that , because of measurement error , frequent monitoring is just as likely to mislead when trying to decide whether changes in treatment are needed ( 2 ) . Most lipid management guidelines clearly state the number and interpretation of initial measurements but are less specific about subsequent monitoring . The National Cholesterol Education Program in the United States suggests that patients can be monitored for response to therapy every 4 to 6 months , or more often if considered necessary , ( 3 ) whereas the Medicare guideline ( 4 ) states The LDL [ low-density lipoprotein ] cholesterol or total cholesterol may be measured three times yearly after treatment goals have been achieved . In the United Kingdom , the PRODIGY ( Prescribing Rationally with Decision Support in General Practice Study ) guidelines ( 5 ) suggest rechecking annually . The Australian National Heart Foundation and the Cardiac Society of Australia and New Zeal and guidelines suggest lipid profile measurement every 6 to 12 months ( 6 ) . However , the basis for recommending these intervals is unclear , and none of the guidelines explicitly describes within-person variability or the likely rates of change in cholesterol levels over time with fixed-dose therapy . We therefore studied the implication s of different strategies for monitoring cholesterol level . Our objectives were to estimate , in patients receiving a fixed dose of cholesterol-lowering medication or placebo , 1 ) the extent to which the initial response to treatment varies among patients ; 2 ) the extent to which the initial response is sustained and long-term change varies within and among patients ; and 3 ) the detectability of these long-term changes in on-treatment cholesterol level ( signal ) , given short-term , within-person variation ( noise ) . Methods We used data from the LIPID ( Long-Term Intervention with Pravastatin in Ischaemic Disease ) trial ( June 1990 to May 1997 ) . The LIPID trial was a r and omized trial of 9014 patients with acute coronary syndromes diagnosed 3 to 36 months previously who had been r and omly assigned to 40 mg of pravastatin or matching placebo and had been followed for an average of 6.0 years ( 7 ) . Before r and omization , patients entered an 8-week placebo run-in phase . For patients to qualify for the study , their plasma total cholesterol levels 4 weeks before r and omization had to be between 4.0 and 7.0 mmol/L ( 155 and 271 mg/dL ) , and the fasting triglyceride level had to be less than 5 mmol/L ( < 443 mg/dL ) . Lipid concentrations ( including concentrations of LDL cholesterol , high-density lipoprotein cholesterol , and triglycerides ) were measured at r and omization , 6 and 12 months later , and then every 12 months for 5 years . We recorded information on adherence to treatment and uptake of other cholesterol-lowering medications . A single laboratory measured all cholesterol concentrations , eliminating differences among laboratories as a source of variation . Estimation for each of the 3 objectives required different methods . Variation in Initial Response to Treatment Patients receiving placebo will show some variation in apparent response that will be attributable to short-term variation . A greater variation of change in total cholesterol level in the pravastatin group indicates some variation in the true response . Therefore , we used the difference in the variance of change from baseline to 6 months between the pravastatin and placebo groups to estimate the variation in true response to treatment with pravastatin . Variation in Long-Term Change within and among Patients After initial response to therapy , the apparent changes in cholesterol level measurements over time comprise 3 components : 1 ) the average , true , long-term change in cholesterol level of the whole group , which we estimated from the group average at each time point ; 2 ) short-term variability , which is a combination of analytic variability and week-to-week biological fluctuation around a stable average ; and 3 ) long-term variability , which is a variation in true , long-term change among individuals ( as would be seen with the theoretical average of a large number of measurements per individual ) . To estimate short-term variability , we used 2 methods . First , we used the cholesterol concentrations during the run-in period ( excluding the first measurement ) , measured only 4 weeks apart , to provide a direct estimate of short-term ( 4-week ) variability . Second , we used a linear extrapolation backward from the longer-term measurements ( variogram method ) ( 8) , to estimate what the apparent variance would be at time 0 . We estimated the long-term variability with a linear mixed-effects model and a direct method . Details and equations are provided in the Appendix . The next sections outline the statistical methods , assumptions , and problems . Modeled Method of Estimation We estimated the components of variance by using a mixed longitudinal model , which assumed that each patient had a linear increase over time but that the rate of increase varied between patients . Specifically , if each patient i has a rate of increase i over time and these rates follow a normal distribution N ( , 1 2 ) , the model was : with Ti again being the true cholesterol measurement at baseline , and it being the error terms for t= 1 , 2 , n i , which are independent from each other even for the same patient . The Appendix gives more details and equations . Direct Method of Estimation The direct method to estimate long-term variability uses the variance of the differences between the baseline value and each subsequent time point , calculated as : ( cholesterol level at time icholesterol level at baseline ) in which the times i are 6 months to 5 years after the stable baseline ( which we have taken as 6 months after treatment for the pravastatin group ) . By subtracting the short-term variability ( described in the previous section ) from this variability of the change , we estimated the additional long-term variability . In general , the direct method and the modeled method gave similar estimates , but the latter estimate seemed to increase too slowly at first and too rapidly later . Alternative functional relationships may be needed . Censored Values Few patients were lost to follow-up . However , to estimate the change for those who were receiving stable treatment , a key issue was patients who withdrew or started taking a non study cholesterol-lowering treatment . To estimate the change , we used 3 methods . First , when patients discontinued or started taking alternative cholesterol-lowering medication , we censored the data and replaced values thereafter with the last value carried forward for each subsequent measurement . Second , we excluded patients who stopped or began taking the study medication . These 2 methods have small ( and opposing ) biases , so we examined any discrepancy between the methods . Third , we performed an extrapolation based on a weighted sum of the group trend and the individual patient 's own trend . Detectability of Long-Term Changes ( Signal ) Given Within-Person Variation ( Noise ) Finally , we aim ed to estimate true- and false-positive rates : the number of patients whose true cholesterol level would or would not exceed an acceptable threshold . After a treated patient 's cholesterol level has stabilized , 2 elements may lead to a true increase in cholesterol level : the average change of the whole group over time and the real variation around the average change . To estimate these , we used the average change ( 0.03 mmol/L [ 1 mg/dL ] per year ) and the true within-person variability ( estimated as described previously ) , and for time points of 1 , 3 , and 5 yearsa normal distribution to estimate the proportion whose true value would or would not have changed beyond that acceptable threshold . For those below or above the target value , we calculated the error rate on the basis of the short-term variability . Role of the Funding Source This work was supported in part by a grant from the Australian National Health and Medical Research Council and a UK National Institute for Health Research program grant . Neither agency had any role in the design , conduct , or interpretation of the study or the decision to su bmi t the manuscript for publication . Results At baseline , 9014 patients with a median age of 62 years ( 83 % male ) and an average pretreatment cholesterol level of 5.65 mmol/L ( SD , 0.82 ; range , 3.0 to 9.2 mmol/L ) ( 218 mg/dL [ SD , 32 ; range , 116 to 355 mg/dL ] ) were r and omly assigned to pravastatin or placebo . Table 1 shows the cholesterol levels over time . Only 1 patient was lost to follow-up , but by year 5 , about 5 % and 6 % of patients had died in the pravastatin and placebo groups , respectively . Table 1 . Average Total Cholesterol Concentrations in the Placebo and Pravastatin Groups in the The effects of pravastatin on plasma lipid levels , in vitro oxidizability of the non-HDL fraction , metabolic control , urinary albumin excretion , and four serum enzymes ( SGPT , SGOT , GT and CPK ) were studied in 20 insulin-dependent diabetic patients ( IDDM ) with incipient nephropathy . The patients were divided into two groups and the study was carried out by a crossover design . After 12 weeks pravastatin treatment ( 20 mg daily ) , plasma cholesterol , LDL-cholesterol and apolipoprotein B ( Apo B ) decreased by 22 , 19 and 15 % , respectively . The thiobarbituric acid reactive substances ( TBARS ) formation and the oxidation lagtime of the non-HDL fraction during the in vitro incubation with copper were not changed before and after treatment . The HbA1c and blood glucose levels , urinary albumin excretion , SGOT , SGPT and GT were not influenced by pravastatin treatment . CPK activity was elevated after 12 weeks of pravastatin treatment , and this elevation persisted even after the 12 weeks placebo period . So , pravastatin could be used as an effective drug for IDDM patients with incipient nephropathy , but close monitoring of the CPK activity is recommended Concerns have been raised because of observations of proteinuria associated with rosuvastatin treatment . In this open-label study , a potential dose-dependent effect was investigated of rosuvastatin on urinary protein excretion and renal function parameters in 90 hyperlipidemic patients r and omly assigned to rosuvastatin 10 mg/day ( n = 45 ) or 20 mg/day ( n = 45 ) . Urinary sample s were collected from patients and 40 age- and gender-matched controls to determine electrolyte , uric acid , creatinine , and protein ( total , albumin , IgG , and α1-microglobulin ) levels at baseline and after 12 weeks . A dose-dependent increase in the excretion of α1-microglobulin ( 17.6 % in rosuvastatin 10 vs 34.9 % in rosuvastatin , 20 mg/day ; P = .03 for the comparison between groups ) was observed . A trend toward an increase in the estimated glomerular filtration rate was noted in only patients receiving 20 mg/day of rosuvastatin . These findings indicate that rosuvastatin treatment increases the urinary excretion of α1-microglobulin urinary excretion in a dose-dependent manner without adversely affecting renal function BACKGROUND In patients with high cholesterol levels , lowering the cholesterol level reduces the risk of coronary events , but the effect of lowering cholesterol levels in the majority of patients with coronary disease , who have average levels , is less clear . METHODS In a double-blind trial lasting five years we administered either 40 mg of pravastatin per day or placebo to 4159 patients ( 3583 men and 576 women ) with myocardial infa rct ion who had plasma total cholesterol levels below 240 mg per deciliter ( mean , 209 ) and low-density lipoprotein ( LDL ) cholesterol levels of 115 to 174 mg per deciliter ( mean , 139 ) . The primary end point was a fatal coronary event or a nonfatal myocardial infa rct ion . RESULTS The frequency of the primary end point was 10.2 percent in the pravastatin group and 13.2 percent in the placebo group , an absolute difference of 3 percentage points and a 24 percent reduction in risk ( 95 percent confidence interval , 9 to 36 percent ; P = 0.003 ) . Coronary bypass surgery was needed in 7.5 percent of the patients in the pravastatin group and 10 percent of those in the placebo group , a 26 percent reduction ( P=0.005 ) , and coronary angioplasty was needed in 8.3 percent of the pravastatin group and 10.5 percent of the placebo group , a 23 percent reduction ( P=0.01 ) . The frequency of stroke was reduced by 31 percent ( P=0.03 ) . There were no significant differences in overall mortality or mortality from noncardiovascular causes . Pravastatin lowered the rate of coronary events more among women than among men . The reduction in coronary events was also greater in patients with higher pretreatment levels of LDL cholesterol . CONCLUSIONS These results demonstrate that the benefit of cholesterol-lowering therapy extends to the majority of patients with coronary disease who have average cholesterol levels The efficacy and safety of lovastatin as a hypolipidemic agent were evaluated in ten adult patients with secondary hypercholesterolemia due to proteinuria ( greater than 2 g/d ) and ( in seven patients ) concurrent corticosteroid therapy . Patients were on a low-cholesterol diet throughout the study . After a 4-week baseline period , patients were r and omized to receive either placebo or 10 mg lovastatin twice daily for a period of 6 weeks . The dose of lovastatin was increased to 20 mg twice daily for 6 weeks , and 40 mg twice daily for 6 weeks in the latter group . Those patients who received placebo for the first 6 weeks subsequently received 10 , 20 , and 40 mg of lovastatin twice daily in a stepped dose regimen , with each dose given for 6 weeks . Lovastatin was well tolerated by all patients and none withdrew from the study . Baseline plasma cholesterol concentrations ( 390 + /- 20 mg/dL ; mean + /- SEM ) decreased 22 % ( P less than 0.003 ) at the lowest dose of 10 mg twice daily , 27 % at 20 mg twice daily , and 33 % at 40 mg twice daily . Baseline plasma triglycerides decreased by 25 % ( P less than 0.05 ) at the highest dosage . Concentrations of low-density lipoprotein ( LDL ) cholesterol fell by 29 % , 34 % , and 45 % on doses of 10 , 20 , and 40 mg of lovastatin twice daily . Concentrations of high-density lipoprotein ( HDL ) cholesterol increased slightly . Serum creatinine concentrations and proteinuria were not affected by lovastatin therapy . We conclude that lovastatin was a well-tolerated and extremely effective hypocholesterolemic agent in patients with persistent secondary hypercholesterolemia associated with proteinuria or proteinuria and concurrent corticosteroid therapy Background . There are few reports on the safety and efficacy of long‐term treatment with statins in patients with chronic renal disease and hyperlipidemia . We evaluated these subjects treated with fluvastatin . Methods . After a 4‐week run‐in period , a total of 80 patients with diabetic nephropathy or chronic glomerulonephritis were r and omly allocated to receive dietary therapy and fluvastatin 20 mg/day ( n = 39 ) , or dietary therapy alone ( n = 41 ) for a period of 48 weeks . Lipid parameters , rhabdomyolysis‐related indicators , 24‐hour urinary albumin excretion and creatinine clearance were measured . The pharmacokinetics of fluvastatin was examined in 8 patients . Results . Creatinine clearance and 24‐hour urinary albumin excretion did not differ between the two groups . The peak serum fluvastatin concentration ( Cmax ) was 141 ± 67 µg/L and the mean AUC0–6 h was 341 ± 149 µg · h/L. Fluvastatin treatment significantly lowered serum total cholesterol , low‐density lipoprotein ( LDL ) cholesterol and apo‐lipoprotein B concentrations by 16 % , 25 % , and 22 % , respectively , compared with patients receiving dietary therapy alone . There were no significant differences in serum triglyceride and high‐density lipoprotein ( HDL ) cholesterol concentrations between the two treatment groups . Serum creatine kinase and aldolase concentrations did not change throughout treatment in both groups . Conclusions . Fluvastatin treatment significantly improved lipid parameters in patients with chronic renal disease . Fluvastatin was well tolerated , with no adverse effects on renal function and no muscular toxicity . However , the drug showed no direct renoprotective effects BACKGROUND In patients with coronary heart disease and a broad range of cholesterol levels , cholesterol-lowering therapy reduces the risk of coronary events , but the effects on mortality from coronary heart disease and overall mortality have remained uncertain . METHODS In a double-blind , r and omized trial , we compared the effects of pravastatin ( 40 mg daily ) with those of a placebo over a mean follow-up period of 6.1 years in 9014 patients who were 31 to 75 years of age . The patients had a history of myocardial infa rct ion or hospitalization for unstable angina and initial plasma total cholesterol levels of 155 to 271 mg per deciliter . Both groups received advice on following a cholesterol-lowering diet . The primary study outcome was mortality from coronary heart disease . RESULTS Death from coronary heart disease occurred in 8.3 percent of the patients in the placebo group and 6.4 percent of those in the pravastatin group , a relative reduction in risk of 24 percent ( 95 percent confidence interval , 12 to 35 percent ; P<0.001 ) . Overall mortality was 14.1 percent in the placebo group and 11.0 percent in the pravastatin group ( relative reduction in risk , 22 percent ; 95 percent confidence interval , 13 to 31 percent ; P<0.001 ) . The incidence of all cardiovascular outcomes was consistently lower among patients assigned to receive pravastatin ; these outcomes included myocardial infa rct ion ( reduction in risk , 29 percent ; P<0.001 ) , death from coronary heart disease or nonfatal myocardial infa rct ion ( a 24 percent reduction in risk , P<0.001 ) , stroke ( a 19 percent reduction in risk , P=0.048 ) , and coronary revascularization ( a 20 percent reduction in risk , P<0.001 ) . The effects of treatment were similar for all predefined subgroups . There were no clinical ly significant adverse effects of treatment with pravastatin . CONCLUSIONS Pravastatin therapy reduced mortality from coronary heart disease and overall mortality , as compared with the rates in the placebo group , as well as the incidence of all prespecified cardiovascular events in patients with a history of myocardial infa rct ion or unstable angina who had a broad range of initial cholesterol levels Coronary artery disease is the most important cause of morbidity and mortality in patients with end-stage renal failure ( RF ) . Hypercholesterolemia is an important risk factor for coronary heart disease . Patients with chronic renal failure ( CRF ) have difficulties in compliance with their care and treatment . Intermittent simvastatin treatment may help to increase compliance and can be a treatment alternative in patients with CRF at risk of coronary artery disease . We investigated the effects of simvastatin and compared intermittent with continuous simvastatin treatment in hypercholesterolamic patients with CRF . The study group included 40 of 422 CRF patients on dialysis in our clinic . The inclusion criterion was low density lipoprotein cholesterol ( LDL-C ) of 130 mg/dL or more . Twenty patients received simvastatin 10 mg/day ( continuous group ) and 20 patients received simvastatin 20 mg three times a week ( only dialysis days- intermittent group ) for four months . Nineteen patients served as controls and they were given a prescribed diet only . Total cholesterol ( TC ) and LDL-C decreased markedly in patients receiving intermittent and continuous simvastatin compared to controls . Continuous simvastatin decreased TC by 23 % ( P < 0.001 ) and LDL-C by 39 % ( P < 0.001 ) . Intermittent simvastatin decreased TC by 26 % ( P < 0.001 ) and LDL-C by 40 % ( P < 0.001 ) . The atherogenic index ratios in both the continuous and intermittent groups ( TC/High density lipoprotein-cholesterol ( HDL-C ) and LDL-C/HDL-C ) decreased significantly . There was no significant difference in patient compliance between the two groups . Intermittent simvastatin is as effective and reliable as continuous simvastatin treatment and can be an alternative treatment in hypercholesterolemic patients on dialysis AIM There are conflicting data regarding the clinical benefit of the effect of HMG-CoA reductase inhibitors ( statins ) in osteoporosis . We have reported that fluvastatin ( a statin ) is effective in improving proteinuria and renal function in childhood IgA nephropathy with mild histological findings and moderate proteinuria . The aim of the present study was to clarify the effect of fluvastatin on the bone mineral density , bone metabolic markers , proteinuria , and renal function of children with minimal change glomerulonephritis with some focal mesangial cell proliferation whose glomeruli did not stain positive for IgA and on moderate proteinuria . PATIENTS AND METHODS We conducted a prospect i ve controlled study of 36 children who had recently been diagnosed with normocholesterolemic minimal change glomerulonephritis with some focal mesangial cell proliferation and moderate proteinuria , and in whom strenuous exercise was restricted . The 36 patients were r and omly assigned to receive 20 mg of fluvastatin ( group 1 ) or 5 mg/kg of dipyridamole ( group 2 ) for two years . RESULTS By the end of the trial , there was no difference in BMD between the groups , and there were no changes in the four bone metabolic parameters . However , the urinary protein , hematuria and BUN levels had significantly decreased in group 1 compared to baseline , and the serum total protein and albumin levels and creatinine clearance had significantly increased in group 1 compared to baseline and group 2 . CONCLUSIONS The results of this study suggest that fluvastatin therapy has an antiproteinuric effect and improves renal function in moderately proteinuric patients with mild histological glomerulonephritis , but does not increase BMD Background / Aim : Urinary liver-type fatty-acid-binding protein ( L-FABP ) is a useful clinical marker in the monitoring of chronic kidney disease ( CKD ) associated with tubulointerstitial damage . Statins have been shown to be effective in the treatment of renal disease . The aim of the present study was to determine whether pitavastatin , a newly developed statin , modulates the urinary L-FABP levels in normolipidemic patients with CKD . Methods : Thirty normolipidemic mild CKD patients ( 18 males and 12 females , mean age 40 years , mean serum creatinine level 1.0 mg/dl ) were r and omly assigned to two groups : ( 1 ) pitavastatin ( 1 mg/day , n = 15 ) and ( 2 ) placebo ( n = 15 ) . Urinary protein and urinary L-FABP levels were measured before the initiation of treatment and 3 and 6 months thereafter . Twenty age-matched healthy subjects were also studied as controls . Results : Before treatment , the urinary L-FABP levels in 30 CKD patients ( 84.0 ± 68.5 µg/g creatinine ) were significantly higher than those of healthy subjects ( 6.4 ± 4.2 µg/g creatinine ; p < 0.001 ) . Pitavastatin slightly reduced serum total cholesterol and triglyceride levels , but this was not statistically significant . However , pitavastatin reduced the urinary protein excretion from 1.8 to 1.0 g/day ( p < 0.01 ) , while the urinary L-FABP levels fell from 88.5 ± 70.5 to 28.0 ± 16.5 µg/g creatinine ( p < 0.01 ) . Conclusion : The present data suggest that pitavastatin ameliorates tubulointerstitial damage in CKD patients independent of the lipid-lowering effect This cost-consequences analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study compares the costs of lovastatin treatment with the costs of cardiovascular hospitalizations and procedures . The cost of lovastatin treatment was defined as the average retail price and the cost of drug safety monitoring and adverse experiences . Costs were determined by actual rates of hospitalizations and procedures . Within a trial , lovastatin treatment cost approximately $ 4,654/patient . Lovastatin treatment significantly reduced the cumulative rate of cardiovascular hospitalizations and procedures ( p = 0.002 ) . Over the duration of the study , the cumulative number of cardiovascular hospitalizations and related therapeutic procedures was significantly reduced by 29 % . The time to first cardiovascular-related hospitalization or procedure was significantly extended by lovastatin ( p = 0.002 ) . Lovastatin reduced the frequency of cardiovascular hospitalization ( 28 % ) , and cardiovascular therapeutic ( 32 % ) and diagnostic procedures ( 23 % ) . Among therapeutic procedures , treatment reduced coronary artery bypass graft surgery by 19 % and percutaneous transluminal coronary angioplasty by 37 % . Total cardiovascular-related hospital days were reduced by 26 % ( p = 0.025 ) . The between-group offset in direct medical costs was $ 524 , which result ed in a 11 % cost offset of lovastatin therapy over the mean study duration of 5.2 years . Lovastatin provides meaningful reductions in cardiovascular-related re source utilization and reductions in direct cardiovascular-related costs associated with the onset of coronary disease Abstract Objective : To estimate the economic efficiency of using pravastatin to prevent the transition from health to cardiovascular disease in men with hypercholesterolaemia . Design : Economic benefit analysis based on data from the West of Scotl and coronary prevention study . Treatment specific hazards of developing cardiovascular disease according to various definitions were estimated . Scottish record linkage data provided disease specific survival . Cost estimates were based on extracontractual tariffs and event specific average lengths of stay calculated from the West of Scotl and coronary prevention study . Subjects : Men with hypercholesterolaemia similar to the subjects in the West of Scotl and coronary prevention study . Main outcome : Cost consequences , the number of transitions from health to cardiovascular disease prevented , the number needed to start treatment , and cost per life year gained . Results : If 10 000 of these men started taking pravastatin , 318 of them would not make the transition from health to cardiovascular disease ( number needed to treat , 31.4 ) , at a net discounted cost of £ 20 m over 5 years . These benefits imply an undiscounted gain of 2460 years of life , and thus £ 8121 per life year gained , or £ 20 375 per life year gained if benefits are discounted . Restriction to the 40 % of men at highest risk reduces the number needed to treat to 22.5 ( £ 5601 per life year gained ( undiscounted ) and £ 13 995 per life year gained ( discounted ) ) . Conclusions : In subjects without evidence of prior myocardial infa rct ion but who have hypercholesterolaemia , the use of pravastatin yields substantial health benefits at a cost that is not prohibitive overall and can be quite efficient in selected high risk subgroups . Key messages The West of Scotl and coronary prevention study showed that pravastatin can prevent cardiovascular disease in men with hypercholesterolaemia So far , reports have deemed this prevention unjustified due to adverse economic implication s This analysis , based on data from the West of Scotl and coronary prevention study and extensive data from the Scottish record linkage system , shows that using pravastatin in this way is worth considering because of its substantial clinical benefit at a reasonable cost Practitioners must now consider using pravastatin to prevent cardiovascular disease in men with hypercholesterolaemia Increased economic efficiency may be obtained by restricting prevention to patients with additional risk BACKGROUND The Sc and inavian Simvastatin Survival Study ( 4S ) demonstrated pronounced reductions in mortality and major coronary events in a cohort of patients with established coronary heart disease ( CHD ) . The present study provides a detailed , post hoc assessment of the efficacy and safety of simvastatin therapy in the following subgroups of 4S patients : those > or = 65 years of age , those < 65 years of age , women , and men . METHODS AND RESULTS The 4S cohort of 4444 CHD patients included 827 women and 1021 patients > or = 65 years of age . Total cholesterol at baseline was 5.5 to 8.0 mmol/L with triglycerides < or = 2.5 mmol/L. Patients were r and omized to therapy with simvastatin 20 to 40 mg daily or placebo for a median follow-up period of 5.4 years . End points consisted of all-cause and CHD mortality , major coronary events ( primarily CHD death and nonfatal myocardial infa rct ion ) , other acute CHD and atherosclerotic events , hospitalizations for CHD and cardiovascular events , and coronary revascularization procedures . Mean changes in serum lipids were similar in the different subgroups . In patients > or = 65 years of age in the simvastatin group , relative risks ( 95 % confidence intervals ) for clinical events were as follows : all-cause mortality , 0.66 ( 0.48 to 0.90 ) ; CHD mortality , 0.57 ( 0.39 to 0.83 ) ; major coronary events , 0.66 ( 0.52 to 0.84 ) ; any atherosclerosis-related event , 0.67 ( 0.56 to 0.81 ) ; and revascularization procedures , 0.59 ( 0.41 to 0.84 ) . In women , the corresponding figures were 1.16 ( 0.68 to 1.99 ) ; 0.86 ( 0.42 to 1.74 ) , 0.66 ( 0.48 to 0.91 ) , 0.71 ( 0.56 to 0.91 ) , and 0.51 ( 0.30 to 0.86 ) , respectively . CONCLUSIONS Cholesterol lowering with simvastatin produced similar reductions in relative risk for major coronary events in women compared with men and in elderly ( > or = 65 years of age ) compared with younger patients . There were too few female deaths to assess the effects on mortality in women . Because mortality rates increased substantially with age , the absolute risk reduction for both all-cause and CHD mortality in simvastatin-treated subjects was approximately twice as great in the older patients The purpose of this trial was to evaluate the effects of fluvastatin on the lipid profile and on renal function , as measured by creatinine clearance , in dyslipidemic patients with chronic renal failure . In this 8-month prospect i ve , open-label , r and omized , parallel-group trial , 130 patients ( 70 men and 60 women ) , after a 2-month washout period following previous lipid-lowering treatments , were r and omly assigned to fluvastatin XL 80 mg given once daily ( 80 patients ) or to st and ard treatment ( 50 patients ) . Mean total cholesterol , low-density lipoprotein ( LDL ) cholesterol , high-density lipoprotein ( HDL ) cholesterol , and triglyceride values after 3 and 6 months of treatment with fluvastatin showed statistically significant improvement compared with st and ard treatment . Improved renal function , as measured by creatinine clearance , was observed at the end of the 6-month treatment period in approximately 65 % of patients treated with fluvastatin . The increase in creatinine clearance consistently reached 10 % to 15 % of baseline values . A statistically significant reduction in C-reactive protein ( CRP ) over baseline values was observed in approximately 75 % of patients treated with fluvastatin . Furthermore , mean values of CRP for the fluvastatin st and ard treatment groups , respectively , were 6.78 and 10.19 at 3 months and 4.47 and 11 at 6 months . Both treatments were well tolerated . No major adverse events were noted . Results of this study suggest that fluvastatin treatment in patients with chronic renal failure is effective in improving the lipid profile , and it demonstrates good safety and tolerability . Furthermore , fluvastatin may contribute to improved nephroprotection in this patient population The factors determining the course of glomerular filtration rate ( GFR ) and albumin excretion rate ( AER ) and the expression of mRNA of slit diaphragm ( SD ) and podocyte proteins in microalbuminuric , hypertensive type II diabetic patients are not fully understood . GFR , AER , and SD protein mRNA were studied in 86 microalbuminuric , hypertensive , type II diabetics at baseline and after 4-year r and om double-blind treatment either with 40 mg simvastatin ( Group 1 ) or with 30 g cholestyramine ( Group 2 ) per day . Both groups had at baseline a GFR decay per year in the previous 2 - 4 years of 3 ml/min/1.73 m(2 ) . Both Groups 1 and 2 showed a significant decrease of low-density lipoprotein cholesterol levels after simvastatin and cholestyramine treatment ( P<0.01 ) . No change from base line values was observed as for hs-C-reactive protein and interleukin-6 . A significant decrease of 8-hydroxydeoxyguanosine urinary excretion was observed after simvastatin treatment . GFR did not change from baseline with simvstatin , whereas a decrease was observed with cholestyramine treatment ( simvastatin vs cholestyramine : -0.21 vs -2.75 ml/min/1.73 m(2 ) , P<0.01 ) . AER decreased in Group 1 ( P<0.01 ) , but not in Group 2 patients . Real-time polymerase chain reaction measurement of mRNA SD proteins ( CD2AP , FAT , Actn 4 , NPHS1 , and NPHS2 ) significantly increased in kidney biopsy specimens after simvastatin , but not cholestyramine treatment . Simvastatin , but not cholestyramine , 4-year treatment maintains steady patterns of GFR , and improves AER and expression of SD proteins in type II diabetes , despite similar hypocholesterolemic effects in circulation This post-hoc analysis of the Treating to New Targets ( TNT ) study evaluated the joint effects of managing low-density lipoprotein cholesterol ( LDL-C ) and systolic blood pressure ( SBP ) on cardiovascular outcomes . Patients ( N=9739 ) with clinical ly evident , stable coronary heart disease ( CHD ) were r and omized to atorvastatin 10 or 80 mg/d . The primary end point was occurrence of a first major cardiovascular event . At 3 months ' follow-up , patients were stratified according to SBP ( < 140 mm Hg vs > or = 140 mm Hg ) and tertiles of LDL-C. At 4.9 years ' median follow-up , the rate of major cardiovascular events was reduced most in patients with lower LDL-C ( P < .001 ) and in patients with SBP < 140 mm Hg ( P = .014 ) . A 42 % relative risk reduction was observed for patients in the lowest LDL-C tertile with an SBP < 140 mm Hg , compared with patients in the highest LDL-C tertile with an SBP > or = 140 mm Hg . The effect of lower SBP on stroke was most pronounced in the lowest LDL-C tertile BACKGROUND AND OBJECTIVES This open , prospect i ve , r and omized trial aim ed to assess the effects of statins in chronic kidney disease patients on optimized antiproteinuric treatment with combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS After 1-month benazepril therapy followed by 1-month benazepril-valsartan combined therapy ( run-in ) , 186 consenting patients with residual proteinuria > 0.5 g/24 h were r and omized to 6-month benazepril-valsartan therapy alone or combined with fluvastatin . Between-groups changes in proteinuria ( primary outcome ) , serum lipids , and GFR were compared by ANCOVA . Analyses were blinded and by intention to treat . RESULTS During the run-in , proteinuria decreased more on benazepril-valsartan than on benazepril alone . Proteinuria reduction correlated with concomitant reduction in total , LDL , and HDL cholesterol , and apolipoprotein B and apolipoprotein A levels . After r and omization , median proteinuria similarly decreased from 1.2 ( 0.6 to 2.2 ) to 1.1 ( 0.5 to 1.7 ) g/24 h on fluvastatin and from 1.5 ( 0.8 to 2.7 ) to 1.0 ( 0.5 to 2.4 ) g/24 h on benazapril-valsartan therapy alone . Fluvastatin further reduced total and LDL cholesterol and apolipoprotein B versus benazepril-valsartan alone , but did not affect serum triglycerides and GFR . Treatment was well tolerated . CONCLUSIONS In chronic kidney disease patients with residual proteinuria despite combined angiotensin-converting enzyme inhibitor and angiotensin receptor blockade therapy , add-on fluvastatin does not affect urinary proteins , but further reduces serum lipids and is safe . Whether combined angiotensin-converting enzyme inhibitor , angiotensin receptor blockade , and statin therapy may improve cardiovascular outcomes in this high-risk population is worth investigating Objective : To examine by secondary analysis of the Treating to New Targets ( TNT ) study whether the benefits of intensive versus st and ard levels of lipid lowering are equally applicable to women . Methods : A total of 10 001 patients ( 1902 women ) with stable coronary heart disease ( CHD ) were r and omised to double-blind treatment with atorvastatin 10 or 80 mg/day for a median follow-up of 4.9 years . Results : In women and men , intensive treatment with atorvastatin 80 mg significantly reduced the rate of major cardiovascular events compared with atorvastatin 10 mg . Among women , the relative and absolute reductions were 27 % and 2.7 % , respectively ( hazard ratio ( HR ) = 0.73 , 95 % confidence interval ( CI ) 0.54 to 1.00 , p = 0.049 ) . In men , the corresponding rate reductions were 21 % and 2.2 % ( HR = 0.79 , 95 % CI 0.69 to 0.91 , p = 0.001 ) . The number needed to treat value ( to prevent one cardiovascular event over 4.9 years compared with patients treated with atorvastatin 10 mg ) for atorvastatin 80 mg was 29 for women and 30 for men . Rates of death of non-cardiovascular origin in the atorvastatin 80 mg and atorvastatin 10 mg were 3.6 % and 1.6 % , respectively ( p = 0.004 ) among women , and 2.8 % and 3.1 % ( p = 0.47 ) among men . Conclusion : Intensive lipid-lowering treatment with atorvastatin 80 mg produced significant reductions in relative risk for major cardiovascular events compared with atorvastatin 10 mg in both women and men with stable CHD The West of Scotl and Coronary Prevention Study is a primary prevention trial design ed to test the hypothesis that reduction of serum cholesterol with pravastatin ( a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ) over an average of 5 years will reduce the incidence of fatal and nonfatal myocardial infa rct ion . At entry , 6,595 men aged 45 - 64 years were r and omized to treatment with either pravastatin ( 40 mg/day ) or placebo . None of the men at entry had evidence of previous myocardial infa rct ion . All were given smoking and dietary advice throughout the study , which will terminate in 1995 . The principal endpoints are : ( 1 ) death due to coronary artery disease ( CAD ) plus nonfatal myocardial infa rct ion ; ( 2 ) death due to CAD ; and ( 3 ) nonfatal myocardial infa rct ion AIMS To investigate the role of HMG-CoA reductase inhibitor ( statin ) treatment during serum glucose variations on plasma oxidized LDL ( ox-LDL ) levels in obese patients with early Type 2 diabetes mellitus ( T2D ) and its relationship to endothelial biomarkers . METHODS In a double-blind , r and omized crossover study , 15 obese diet-treated T2D patients received cerivastatin ( 0.4 mg/day ) or placebo for 3 months . Circulating ox-LDL levels were measured fasting and during a euglycaemic-hyperinsulinaemic clamp ( approximately 5.5 mmol/l ; EHC ) and a hyperglycemic clamp ( approximately 20 mmol/l ; HC ) . An endothelium-dependent flow-mediated dilation ( FMD ) study was carried out and urinary albumin excretion ( UAE ) was measured at rest and during EHC . S-ICAM , s-VCAM and basal prothrombotic factors were also measured . RESULTS During cerivastatin treatment , basal circulating ox-LDL levels decreased by 48 % ( P<0.001 ) compared with placebo . Serum ox-LDL levels decreased during EHC and remained unchanged during HC compared with the fasting state ; with cerivastatin treatment these levels were lower compared with placebo both in the fasting state and during the clamp studies . FMD was higher with cerivastatin than with placebo ( P<0.001 ) and the increments in FMD correlated with decrements in serum ox-LDL levels ( r=0.78 , P=0.001 ) . Microalbuminuria increased during EHC but this was blunted during cerivastatin therapy compared with placebo ( P<0.05 ) . Basal sICAM-1 and sVCAM-1 levels decreased ( P<0.01 and P<0.05 , respectively ) . CONCLUSIONS In early obese Type 2 diabetic patients , serum ox-LDL levels are influenced by short-term serum glucose variations and lowered with cerivastatin therapy . During cerivastatin treatment , improved flow-mediated endothelium-dependent dilation was associated with decrements in circulating ox-LDL levels and the hyperinsulinaemia-induced urinary albumin excretion was blunted BACKGROUND Advances in the treatment of cardiovascular disease have increased costs ; annual cardiovascular healthcare expenditure in the United States currently exceeds $ 100 billion . Physicians and third-party payers need to assess the economic impact of treatments that reduce cardiovascular morbidity and mortality . METHODS AND RESULTS The Sc and inavian Simvastatin Survival Study is a r and omized , double-blind , placebo-controlled trial in which simvastatin reduced the risk of death by 30 % ( P=.0003 ) over the median follow-up period of 5.4 years in patients with previous myocardial infa rct ion or stable angina pectoris as a result of a 42 % reduction in the risk of coronary deaths ( P=.00001 ) . In the present report , data prospect ively collected from hospital admissions were analyzed to evaluate the impact of simvastatin on healthcare re source use and perform a cost-minimization analysis . In the placebo group ( n=2223 ) , there were 1905 hospitalizations ( average duration , 7.9 days ) for acute cardiovascular events or coronary revascularization procedures among 937 patients , whereas in the simvastatin group ( n=2221 ) , there were 1403 such hospitalizations ( average duration , 7.1 days ) among 720 patients ( all differences , P<.0001 ) . The corresponding number of hospital days was 15089 and 9951 in the two groups , respectively ( 34 % reduction , P<.0001 ) . In the United States , the result ing reduction in hospitalization costs over the 5.4 years of the trial would be $ 3872 per patient , reducing the effective cost of simvastatin by 88 % to $ 0.28 per day . CONCLUSIONS In addition to reducing mortality and morbidity in coronary heart disease patients , simvastatin markedly reduces use of hospital services , thus off setting most of its cost The MEGA Study was Japan 's first primary prevention trial of cardiovascular disease ( CVD ) by cholesterol lowering with low-dose pravastatin . Included were postmenopausal women aged < or = 70 years and men aged 40 - 70 years with mildly elevated total cholesterol ( TC ) level 220 - 270 mg/dL. In all , 8214 out patients were r and omly assigned to receive diet alone or diet plus pravastatin 10 - 20mg/day for an average follow-up of 5.3 years . The primary endpoint was a composite of fatal and nonfatal MI , angina , cardiac and sudden death , and coronary revascularization . TC was reduced by 11.5 % in the diet plus pravastatin group versus 2.1 % in the diet alone group . LDL-C was reduced by 18 % and 3.2 % in the two groups , respectively . TC was reduced to < 220 mg/dL and LDL-C to < 130 mg/dL in patients in the diet plus pravastatin group . There was a significant 33 % reduction of the primary endpoint in the diet plus pravastatin group compared with the diet alone group . Notable findings of the MEGA Study included the observation that despite pravastatin 's modest LDL-C reductions in this low-risk population , a 33 % reduction of CHD events was achieved . Even though 68 % of patients were women , who have been traditionally considered at less risk than men , significant CHD risk reduction was observed across all groups AIM Central pulse pressure and measures of arterial stiffness ( augmentation index ( AIx ) and aortic pulse wave velocity ( PWV ) ) predict morbidity and mortality in patients with stage 2 - 4 chronic kidney disease ( CKD ) . Although statin therapy may be of vascular benefit in patients with CKD , the long-term effect of statins on central pulse pressure and arterial stiffness has not been assessed in this patient population . Hence , the aim of this study was to assess the long-term effects of atorvastatin on arterial stiffness and central blood pressure in patients with CKD . METHODS We enrolled 37 patients with serum creatinine levels > 1.36 mg/dL into a r and omized , double blind trial . Patients were allocated to receive 10 mg of atorvastatin per day ( 19 ) or placebo ( 18 ) for three years . Aortic PWV , AIx , estimated central and brachial blood pressures and were determined every nine months . RESULTS At baseline , there were no significant differences in aortic PWV , AIx , central or brachial blood pressures between atorvastatin-treated and placebo-treated patients . During the trial , aortic PWV significantly ( p=0.05 ) increased in placebo-treated , but not ( p=0.10 ) in atorvastatin-treated patients ( 0.51+/-0.95 vs. 0.30+/-0.75 m/sec/yr ; p=0.48 ) . This represented a 41 % ( but not statistically significant ) slowing of the rate of increase in aortic stiffness . There were no significant changes between groups in the rate of change of AIx ( atorvastatin -0.15+/-5.65 vs. placebo 0.39+/-5.38%/yr , p=0.53 ) or central pulse pressure ( atorvastatin -2.32+/-7.46 vs. placebo -0.36+/-6.64 mmHg/yr p= 0.61 ) . CONCLUSION In patients with CKD arterial stiffness measured by aortic PWV showed a significant increase over time in placebo-treated patients but not in atorvastatin-treated patients Summary The aim of this study was to assess the effect of simvastatin on plasma lipoproteins and renal function in hypercholesterolaemic Type 1 ( insulin-dependent ) diabetic patients with diabetic nephropathy . Twenty-six hypercholesterolaemic ( total cholesterol ≽ 5.5 mmol/l ) Type 1 diabetic patients with nephropathy were enrolled in a double-blind r and omized placebo-controlled study for 12 weeks . The active treatment group ( n -14 ) received simvastatin ( 10–20 mg/day ) for 12 weeks while the remaining 12 patients received treatment with placebo . The results during simvastatin treatment ( baseline vs 12 weeks ) : total cholesterol 6.6 vs 4.8 mmol/1 ( p < 0.01 ) , LDL-cholesterol 4.25 vs 2.57 mmol/l ( p < 0.01 ) and apolipoprotein B 1.37 vs 1.06 mmol/l ( p < 0.01 ) . HDL-cholesterol , and apolipoprotein A-I remained unchanged . Total cholesterol , LDL-cholesterol , HDL-cholesterol , apolipoprotein A – I , apolipoprotein B remained unchanged during placebo treatment . Albuminuria measured during the simvastatin and the placebo treatment ( baseline vs 12 weeks ) ( the data are logarithmically transformed before analysis because of their positively skewed transformation ; geometric mean ( ×/÷ antilog SE ) is indicated ) was 458 ( ×/÷ 1.58 ) vs 393 ( ×/÷ 1.61 ) and 481 ( ×/÷ 1.62 ) vs 368 ( ×/÷ 1.78 μg/min ( NS ) . Glomerular filtration rate during simvastatin and placebo treatment ( baseline vs 12 weeks ) was 64 vs 63 and 72 vs 74 ml·min−1·1.73 m−2 , respectively . Two patients receiving simvastatin treatment were withdrawn , one due to gastrointestinal side effects and one due to myalgia . In conclusion , our short-term study in Type 1 diabetic patients with diabetic nephropathy did not reveal any beneficial effect on albuminuria despite a striking lipid-lowering effect of simvastatin in diabetic nephropathy Patients with nephrotic-range proteinuria have impaired clearance of triglyceride-rich lipoproteins . This results in the atherogenic lipoprotein phenotype ( mild hypertriglyceridemia , low high-density lipoproteins [ HDL ] , and excess small , dense low-density lipoproteins [ LDLIII ] ) . Excess remnant lipoproteins ( RLP ) are linked to hypertriglyceridemia and may contribute to the atherogenicity of nephrotic dyslipidemia . A r and omized crossover study compared the effects of a statin ( cerivastatin ) and a fibrate ( fenofibrate ) on LDLIII and RLP in 12 patients with nephrotic-range proteinuria . Cerivastatin reduced cholesterol ( 21 % , P : < 0.01 ) , triglyceride ( 14 % , P : < 0.05 ) , LDL cholesterol ( LDL-C ; 23 % , P : < 0.01 ) , total LDL ( 18 % , P : < 0.01 ) , and LDLIII concentration ( 27 % P : < 0.01 ) . % LDLIII , RLP-C , and RLP triglyceride ( RLP-TG ) were unchanged . Plasma LDLIII reduction with cerivastatin treatment correlated with LDL-C reduction ( r(2 ) = 34 % , P : < 0.05 ) . Fenofibrate lowered cholesterol ( 19 % ) , triglyceride ( 41 % ) , very low-density lipoprotein cholesterol ( 52 % ) , LDLIII concentration ( 49 % ) , RLP-C ( 35 % ) , and RLP-TG ( 44 % ; all P : < 0.01 ) . Fenofibrate also reduced % LDLIII from 60 to 33 % ( P : < 0.01 ) . HDL-C ( 19 % , P : < 0.01 ) increased with fenofibrate treatment ; LDL-C and total LDL were unchanged . The reduction in LDLIII concentration and RLP-C with fenofibrate treatment correlated with plasma triglyceride reduction ( LDLIII r(2 ) = 67 % , P : < 0.001 ; RLP cholesterol r(2 ) = 58 % , P : < 0.005 ) . Serum creatinine increased with fenofibrate treatment ( 14 % , P : < 0.01 ) ; however , creatinine clearance was unchanged . LDLIII concentration was 187 + /- 85 mg/dl after cerivastatin treatment and 133 + /- 95 mg/dl after fenofibrate treatment . Cerivastatin and fenofibrate reduce LDLIII concentration in nephrotic-range proteinuria . However , atherogenic concentrations of LDLIII remain prevalent after either treatment . Fenofibrate but not cerivastatin reduces remnant lipoproteins . The two treatments seem to reduce LDLIII by different mechanisms , suggesting a potential role for combination therapy to optimize lowering of LDLIII and RLP 3‐Hydroxy‐3‐methylglutaryl coenzyme A ( HMG‐CoA ) reductase inhibitors are established drugs for the treatment of hypercholesterolemia , but several studies have shown that benefits obtained with these drugs are not causally related only to regression of cholesterol lowering . Moreover , in experimental models of progressive renal disease , statins have reduced the extent of glomerulosclerosis . This study evaluated the antiproteinuric effect of a daily dose of 40 mg fluvastatin for 6 months in moderately proteinuric patients with immunoglobulin A nephropathy , stable renal function , and no indicators of poor long‐term prognosis . The effects of therapy were evaluated on the basis of 24‐hour proteinuria ( total proteinuria and albuminuria ) , albuminemia , creatinine clearance , cholesterol , and triglyceride values . Renal function remained stable in all patients . A significant decrease in proteinuria was observed after 6 months of therapy and persisted for all the observations . An increase in serum albumin was observed after 6 months of therapy . This study suggests that there is an antiproteinuric effect of HMG‐CoA reductase inhibitors in moderately proteinuric patients with immunoglobulin A nephropathy . ( Clin Pharmacol Ther 2000;67:427‐31 . CONTEXT Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality , but the optimal first-step therapy is unknown . OBJECTIVE To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease ( CHD ) or other cardiovascular disease ( CVD ) events vs treatment with a diuretic . DESIGN The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , a r and omized , double-blind , active-controlled clinical trial conducted from February 1994 through March 2002 . SETTING AND PARTICIPANTS A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers . INTERVENTIONS Participants were r and omly assigned to receive chlorthalidone , 12.5 to 25 mg/d ( n = 15 255 ) ; amlodipine , 2.5 to 10 mg/d ( n = 9048 ) ; or lisinopril , 10 to 40 mg/d ( n = 9054 ) for planned follow-up of approximately 4 to 8 years . MAIN OUTCOME MEASURES The primary outcome was combined fatal CHD or nonfatal myocardial infa rct ion , analyzed by intent-to-treat . Secondary outcomes were all-cause mortality , stroke , combined CHD ( primary outcome , coronary revascularization , or angina with hospitalization ) , and combined CVD ( combined CHD , stroke , treated angina without hospitalization , heart failure [ HF ] , and peripheral arterial disease ) . RESULTS Mean follow-up was 4.9 years . The primary outcome occurred in 2956 participants , with no difference between treatments . Compared with chlorthalidone ( 6-year rate , 11.5 % ) , the relative risks ( RRs ) were 0.98 ( 95 % CI , 0.90 - 1.07 ) for amlodipine ( 6-year rate , 11.3 % ) and 0.99 ( 95 % CI , 0.91 - 1.08 ) for lisinopril ( 6-year rate , 11.4 % ) . Likewise , all-cause mortality did not differ between groups . Five-year systolic blood pressures were significantly higher in the amlodipine ( 0.8 mm Hg , P = .03 ) and lisinopril ( 2 mm Hg , P<.001 ) groups compared with chlorthalidone , and 5-year diastolic blood pressure was significantly lower with amlodipine ( 0.8 mm Hg , P<.001 ) . For amlodipine vs chlorthalidone , secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine ( 10.2 % vs 7.7 % ; RR , 1.38 ; 95 % CI , 1.25 - 1.52 ) . For lisinopril vs chlorthalidone , lisinopril had higher 6-year rates of combined CVD ( 33.3 % vs 30.9 % ; RR , 1.10 ; 95 % CI , 1.05 - 1.16 ) ; stroke ( 6.3 % vs 5.6 % ; RR , 1.15 ; 95 % CI , 1.02 - 1.30 ) ; and HF ( 8.7 % vs 7.7 % ; RR , 1.19 ; 95 % CI , 1.07 - 1.31 ) . CONCLUSION Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive . They should be preferred for first-step antihypertensive therapy Objective To determine the cardiovascular benefits of atorvastatin stratified by blood pressure-lowering regimen , 2.2 years after closure of the lipid-lowering arm ( LLA ) of the Anglo-Sc and inavian Cardiac Outcomes Trial ( ASCOT-LLA ) . Methods In ASCOT-LLA , 10 305 hypertensive patients r and omized to amlodipine-based or atenolol-based therapy and with a total cholesterol 6.5 mmol/l or less were further r and omized to atorvastatin or placebo . ASCOT-LLA was terminated after 3.3 years median follow-up . Cardiovascular outcomes in these patients were further evaluated 2.2 years later , at the end of the blood pressure-lowering arm ( BPLA ) . Results By the end of BPLA in both groups originally assigned statin or placebo , approximately 65 % were receiving a statin , and lipid levels had equalized . The benefits of atorvastatin observed in LLA were sustained throughout BPLA . At the end of BPLA , in those assigned amlodipine-based therapy , atorvastatin reduced coronary heart disease deaths and nonfatal myocardial infa rct ion ( MI ) by 46 % [ hazard ratio 0.54 , confidence interval ( CI ) 0.40–0.72 , P < 0.0001 ] , stroke by 37 % [ hazard ratio 0.63 , CI 0.46–0.87 , P = 0.004 ] and total cardiovascular events and procedures by 27 % [ hazard ratio 0.73 , CI 0.63–0.86 , P < 0.0001 ] . In the atenolol-based group , atorvastatin reduced coronary heart disease death and nonfatal MI by 25 % [ hazard ratio 0.75 , CI 0.57–0.97 , P = 0.03 ] , stroke by 10 % [ hazard ratio 0.90 , CI 0.69–1.18 , P = 0.43 ] and total cardiovascular events and procedures by 13 % [ hazard ratio 0.87 , CI 0.76–1.0 , P = 0.05 ] . P values for heterogeneity were low , but failed to achieve statistical significance ( 0.10 , 0.10 and 0.11 for chronic heart disease , stroke and total cardiovascular events , respectively ) . Conclusion Although not statistically significant , the benefits of atorvastatin appeared greater among those on amlodipine-based compared with atenolol-based therapy . These data provide supporting evidence that coassignment to atorvastatin may have generated differential effects on coronary and other cardiovascular outcomes by amlodipine-based and atenolol-based treatment in ASCOT-BPLA Background : Cardiovascular disease ( CVD ) is the leading cause of death in patients with end-stage renal disease ( ESRD ) . Aims : AURORA ( A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis : an Assessment of survival and cardiovascular events ) is the first large-scale international trial to assess the effects of statins on cardiovascular outcomes in patients with ESRD on chronic haemodialysis . Preliminary baseline data from the r and omised population are presented . Methods : A total of 2,775 patients from 280 centres in 25 countries were r and omised into the study . Patients aged 50–80 years on regular chronic haemodialysis for at least 3 months before screening were eligible for inclusion . They were r and omised 1:1 to receive either rosuvastatin 10 mg or placebo daily and assessed throughout the study . Results : The mean age at baseline was 64 years . Most patients were male ( 62 % ) and 85 % were white . The median time since commencing renal replacement was 32 months . Mean total cholesterol ( TC ) and low-density lipoprotein cholesterol ( LDL-C ) levels were 4.53 mmol/l ( 175 mg/dl ) and 2.57 mmol/l ( 99 mg/dl ) , respectively . Conclusion : Results from the AURORA trial will impact on the current guidelines and use of statins in this patient population Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol decreases the incidence of coronary heart disease in patients with elevated plasma cholesterol . However , it is not known whether patients with established coronary artery disease and normal plasma cholesterol can be benefited . Several previous prevention trials review ed in this report found that patients who had plasma cholesterol levels at baseline in the upper portion of the eligibility range ( e.g. , greater than 240 mg/dl ) received greater benefit from hypolipidemic diet or drug therapy than patients who had lower plasma cholesterol levels at baseline . The recent availability of drugs that are more potent and less prone to cause adverse reactions than previous regimens permits this important question to be addressed . The Cholesterol and Recurrent Events trial is testing whether pravastatin , a hydroxymethylglutaryl coenzyme A reductase inhibitor , will decrease the sum of fatal coronary heart disease and nonfatal myocardial infa rct ion ( MI ) in patients who have recovered from a MI and who have normal total cholesterol levels . Fatal cardiovascular disease and total mortality are important secondary end points . The trial is enrolling 4,000 men and women from 80 centers throughout North America , age 21 to 75 years , who have survived MI for 3 to 20 months , who have plasma total cholesterol less than 240 mg/dl ( 6.2 mmol/liter ) and low-density cholesterol of 115 to 174 mg/dl ( 3.0 to 4.5 mmol/liter ) , and who are representative of the general population of patients with MI . Patients are r and omized to either active or inactive drug therapy . Active therapy consists of pravastatin , 40 mg/day , design ed to achieve an average decrease in low-density lipoprotein cholesterol of approximately 30 % , and an increase in high-density lipoprotein of 5 % . The average duration of follow-up will be greater than or equal to 5 years . To protect against a lower than expected rate of recurrent events , the trial will be continued until a predetermined fixed number of coronary heart disease events occurs in the entire cohort so that the original sensitivity of the trial will be maintained BACKGROUND Individuals with diabetes are at increased risk of cardiovascular morbidity and mortality , although typically their plasma concentrations of LDL cholesterol are similar to those in the general population . Previous evidence about the effects of lowering cholesterol in people with diabetes has been limited , and most diabetic patients do not currently receive cholesterol-lowering therapy despite their increased risk . METHODS 5963 UK adults ( aged 40 - 80 years ) known to have diabetes , and an additional 14573 with occlusive arterial disease ( but no diagnosed diabetes ) , were r and omly allocated to receive 40 mg simvastatin daily or matching placebo . Prespecified analyses in these prior disease subcategories , and other relevant subcategories , were of first major coronary event ( ie , non-fatal myocardial infa rct ion or coronary death ) and of first major vascular event ( ie , major coronary event , stroke or revascularisation ) . Analyses were also conducted of subsequent vascular events during the scheduled treatment period . Comparisons are of all simvastatin-allocated versus all placebo-allocated participants ( ie , intention to treat ) , which yielded an average difference in LDL cholesterol of 1.0 mmol/L ( 39 mg/dL ) during the 5-year treatment period . FINDINGS Both among the participants who presented with diabetes and among those who did not , there were highly significant reductions of about a quarter in the first event rate for major coronary events , for strokes , and for revascularisations . For the first occurrence of any of these major vascular events among participants with diabetes , there was a definite 22 % ( 95 % CI 13 - 30 ) reduction in the event rate ( 601 [ 20.2 % ] simvastatin-allocated vs 748 [ 25.1 % ] placebo-allocated , p<0.0001 ) , which was similar to that among the other high-risk individuals studied . There were also highly significant reductions of 33 % ( 95 % CI 17 - 46 , p=0.0003 ) among the 2912 diabetic participants who did not have any diagnosed occlusive arterial disease at entry , and of 27 % ( 95 % CI 13 - 40 , p=0.0007 ) among the 2426 diabetic participants whose pretreatment LDL cholesterol concentration was below 3.0 mmol/L ( 116 mg/dL ) . The proportional reduction in risk was also about a quarter among various other subcategories of diabetic patient studied , including : those with different duration , type , or control of diabetes ; those aged over 65 years at entry or with hypertension ; and those with total cholesterol below 5.0 mmol/L ( 193 mg/dL ) . In addition , among participants who had a first major vascular event following r and omisation , allocation to simvastatin reduced the rate of subsequent events during the scheduled treatment period . INTERPRETATION The present study provides direct evidence that cholesterol-lowering therapy is beneficial for people with diabetes even if they do not already have manifest coronary disease or high cholesterol concentrations . Allocation to 40 mg simvastatin daily reduced the rate of first major vascular events by about a quarter in a wide range of diabetic patients studied . After making allowance for non-compliance , actual use of this statin regimen would probably reduce these rates by about a third . For example , among the type of diabetic patient studied without occlusive arterial disease , 5 years of treatment would be expected to prevent about 45 people per 1000 from having at least one major vascular event ( and , among these 45 people , to prevent about 70 first or subsequent events during this treatment period ) . Statin therapy should now be considered routinely for all diabetic patients at sufficiently high risk of major vascular events , irrespective of their initial cholesterol concentrations BACKGROUND Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk . However , a benefit of statins in such patients who are undergoing hemodialysis has not been proved . METHODS We conducted an international , multicenter , r and omized , double-blind , prospect i ve trial involving 2776 patients , 50 to 80 years of age , who were undergoing maintenance hemodialysis . We r and omly assigned patients to receive rosuvastatin , 10 mg daily , or placebo . The combined primary end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . Secondary end points included death from all causes and individual cardiac and vascular events . RESULTS After 3 months , the mean reduction in low-density lipoprotein ( LDL ) cholesterol levels was 43 % in patients receiving rosuvastatin , from a mean baseline level of 100 mg per deciliter ( 2.6 mmol per liter ) . During a median follow-up period of 3.8 years , 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point ( 9.2 and 9.5 events per 100 patient-years , respectively ; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group , 0.96 ; 95 % confidence interval [ CI ] , 0.84 to 1.11 ; P=0.59 ) . Rosuvastatin had no effect on individual components of the primary end point . There was also no significant effect on all-cause mortality ( 13.5 vs. 14.0 events per 100 patient-years ; hazard ratio , 0.96 ; 95 % CI , 0.86 to 1.07 ; P=0.51 ) . CONCLUSIONS In patients undergoing hemodialysis , the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . ( Clinical Trials.gov number , NCT00240331 . BACKGROUND Controversy persists regarding the extent of shared pathways between arterial and venous thrombosis and whether treatments of known efficacy for one disease process have consistent benefits for the other . Observational studies have yielded variable estimates of the effect of statin therapy on the risk of venous thromboembolism , and evidence from r and omized trials is lacking . METHODS We r and omly assigned 17,802 apparently healthy men and women with both low-density lipoprotein ( LDL ) cholesterol levels of less than 130 mg per deciliter ( 3.4 mmol per liter ) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to receive rosuvastatin , 20 mg per day , or placebo . We followed participants for the first occurrence of pulmonary embolism or deep-vein thrombosis and performed analyses of the data on an intention-to-treat basis . RESULTS During a median follow-up period of 1.9 years ( maximum , 5.0 ) , symptomatic venous thromboembolism occurred in 94 participants : 34 in the rosuvastatin group and 60 in the placebo group . The rates of venous thromboembolism were 0.18 and 0.32 event per 100 person-years of follow-up in the rosuvastatin and placebo groups , respectively ( hazard ratio with rosuvastatin , 0.57 ; 95 % confidence interval [ CI ] , 0.37 to 0.86 ; P=0.007 ) ; the corresponding rates for unprovoked venous thromboembolism ( i.e. , occurring in the absence of a known malignant condition , trauma , hospitalization , or surgery ) were 0.10 and 0.17 ( hazard ratio , 0.61 ; 95 % CI , 0.35 to 1.09 ; P=0.09 ) and for provoked venous thromboembolism ( i.e. , occurring in patients with cancer or during or shortly after trauma , hospitalization , or surgery ) , 0.08 and 0.16 ( hazard ratio , 0.52 ; 95 % CI , 0.28 to 0.96 ; P=0.03 ) . The rates of pulmonary embolism were 0.09 in the rosuvastatin group and 0.12 in the placebo group ( hazard ratio , 0.77 ; 95 % CI , 0.41 to 1.45 ; P=0.42 ) , whereas the rates of deep-vein thrombosis only were 0.09 and 0.20 , respectively ( hazard ratio , 0.45 ; 95 % CI , 0.25 to 0.79 ; P=0.004 ) . Consistent effects were observed in all the subgroups examined . No significant differences were seen between treatment groups in the rates of bleeding episodes . CONCLUSIONS In this trial of apparently healthy persons , rosuvastatin significantly reduced the occurrence of symptomatic venous thromboembolism . ( Clinical Trials.gov number , NCT00239681 . The West of Scotl and Coronary Prevention Study recently demonstrated the benefits of pravastatin therapy in the prevention of coronary heart disease events in middle-aged hypercholesterolemic men without prior myocardial infa rct ion . We present an analysis of the influence of baseline risk factors on coronary events and total mortality in the trial , and their interaction with therapy , using the Cox proportional hazards model . The multivariate predictors of fatal or nonfatal coronary events were treatment allocation ( pravastatin or placebo ) , current smoking , diabetes mellitus , nitrate consumption , minor electrocardiographic abnormalities , angina pectoris , family history of premature coronary death , widowhood , blood pressure , and total cholesterol/high density lipoprotein cholesterol ratio . Independent of other risk factors , pravastatin reduced the risk of definite coronary heart disease death or nonfatal myocardial infa rct ion by 32 % ( 95 % confidence interval 17 to 44 , p = 0.0001 ) , definite or suspected coronary heart disease death by 35 % ( 3 to 56 , p = 0.035 ) , cardiovascular death by 33 % ( 4 to 53 , p = 0.027 ) , coronary revascularization procedures by 38 % ( 11 to 56 , p = 0.009 ) , and all-cause mortality by 24 % ( 2 to 41 , p = 0.037 ) . The 5-year risk of fatal or nonfatal myocardial infa rct ion , calculated using the predictors identified in the Cox analysis , ranged from < 4.4 % in the lowest quartile of risk to > 9.6 % in the highest quartile . The proportional benefit achieved by pravastatin was independent of other risk factors ; hence , the absolute benefit of therapy was greatest in subjects with the highest baseline risk . Such subjects can be identified easily in the population and deserve high priority for treatment BACKGROUND Type 2 diabetes is associated with a substantially increased risk of cardiovascular disease , but the role of lipid-lowering therapy with statins for the primary prevention of cardiovascular disease in diabetes is inadequately defined . We aim ed to assess the effectiveness of atorvastatin 10 mg daily for primary prevention of major cardiovascular events in patients with type 2 diabetes without high concentrations of LDL-cholesterol . METHODS 2838 patients aged 40 - 75 years in 132 centres in the UK and Irel and were r and omised to placebo ( n=1410 ) or atorvastatin 10 mg daily ( n=1428 ) . Study entrants had no documented previous history of cardiovascular disease , an LDL-cholesterol concentration of 4.14 mmol/L or lower , a fasting triglyceride amount of 6.78 mmol/L or less , and at least one of the following : retinopathy , albuminuria , current smoking , or hypertension . The primary endpoint was time to first occurrence of the following : acute coronary heart disease events , coronary revascularisation , or stroke . Analysis was by intention to treat . FINDINGS The trial was terminated 2 years earlier than expected because the prespecified early stopping rule for efficacy had been met . Median duration of follow-up was 3.9 years ( IQR 3.0 - 4.7 ) . 127 patients allocated placebo ( 2.46 per 100 person-years at risk ) and 83 allocated atorvastatin ( 1.54 per 100 person-years at risk ) had at least one major cardiovascular event ( rate reduction 37 % [ 95 % CI -52 to -17 ] , p=0.001 ) . Treatment would be expected to prevent at least 37 major vascular events per 1000 such people treated for 4 years . Assessed separately , acute coronary heart disease events were reduced by 36 % ( -55 to -9 ) , coronary revascularisations by 31 % ( -59 to 16 ) , and rate of stroke by 48 % ( -69 to -11 ) . Atorvastatin reduced the death rate by 27 % ( -48 to 1 , p=0.059 ) . No excess of adverse events was noted in the atorvastatin group . INTERPRETATION Atorvastatin 10 mg daily is safe and efficacious in reducing the risk of first cardiovascular disease events , including stroke , in patients with type 2 diabetes without high LDL-cholesterol . No justification is available for having a particular threshold level of LDL-cholesterol as the sole arbiter of which patients with type 2 diabetes should receive statins . The debate about whether all people with this disorder warrant statin treatment should now focus on whether any patients are at sufficiently low risk for this treatment to be withheld BACKGROUND The West of Scotl and Coronary Prevention Study was a primary prevention trial that demonstrated the effectiveness of pravastatin ( 40 mg/d ) in reducing morbidity and mortality from coronary heart disease ( CHD ) in moderately hypercholesterolemic men . The present analysis examines the extent to which differences in LDL and other plasma lipids both at baseline and on treatment influenced CHD risk reduction . METHODS AND RESULTS Relationships between baseline lipid concentrations and incidence of all cardiovascular events and between on-treatment lipid concentrations and risk reduction in patients taking pravastatin were examined by use of Cox regression models and by division of the cohort into quintiles . Variation in plasma lipids at baseline did not influence the relative risk reduction generated by pravastatin therapy . Fall in LDL level in the pravastatin-treated group did not correlate with CHD risk reduction in multivariate regression . Furthermore , maximum benefit of an approximately 45 % risk reduction was observed in the middle quintile of LDL reduction ( mean 24 % fall ) ; further mean decrements in LDL ( up to 39 % ) were not associated with a greater decrease in CHD risk . Comparison of event rates between placebo- and pravastatin-treated subjects with the same LDL cholesterol level provided evidence for an apparent treatment effect that was independent of LDL . CONCLUSIONS We conclude that the treatment effect of 40 mg/d of pravastatin is proportionally the same regardless of baseline lipid phenotype . There is no CHD risk reduction unless LDL levels are reduced , but a fall in the range of 24 % is sufficient to produce the full benefit in patients taking this dose of pravastatin . LDL reduction alone does not appear to account entirely for the benefits of pravastatin therapy BACKGROUND We examined whether atorvastatin affects diabetic kidney disease and whether the effect of atorvastatin on cardiovascular disease ( CVD ) varies by kidney status in patients with diabetes . STUDY DESIGN The Collaborative Atorvastatin Diabetes Study ( CARDS ) r and omized placebo-controlled trial . SETTING & PARTICIPANTS Patients with type 2 diabetes and no prior CVD ( n = 2,838 ) . INTERVENTION R and om allocation to atorvastatin , 10 mg/d , or placebo , with a median follow-up of 3.9 years . OUTCOMES Estimated glomerular filtration rate ( eGFR ) , albuminuria , CVD . MEASUREMENTS Baseline and follow-up GFRs were estimated by using the Modification of Diet in Renal Disease Study equation . Urinary albumin-creatinine ratio was measured on spot urine sample s. RESULTS At baseline , 34 % of patients had an eGFR of 30 to 60 mL/min/1.73 m(2 ) . Atorvastatin treatment was associated with a modest improvement in annual change in eGFR ( net , 0.18 mL/min/1.73 m(2)/y ; 95 % confidence interval [ CI ] , 0.04 to 0.32 ; P = 0.01 ) that was most apparent in those with albuminuria ( net improvement , 0.38 mL/min/1.73 m(2)/y ; P = 0.03 ) . At baseline , 21.5 % of patients had albuminuria and an additional 6.8 % developed albuminuria during follow-up . Atorvastatin did not influence the incidence of albuminuria ( hazard ratio , 1.49 ; 95 % CI , 0.73 to 3.04 ; P = 0.3 ) or regression to normoalbuminuria ( hazard ratio , 1.19 ; 95 % CI , 0.57 to 2.49 ; P = 0.6 ) . In 970 patients with a moderately decreased eGFR of 30 to 60 mL/min/1.73 m(2 ) , there was a 42 % reduction in major CVD events with treatment , including a 61 % reduction in stroke . This treatment effect was similar to the 37 % ( 95 % CI , 17 to 52 ; P < 0.001 ) reduction in CVD observed in the study overall ( P = 0.4 for the eGFR-treatment interaction ) . LIMITATIONS Low incidence rates of albuminuria and transition to more severe kidney status limit power to detect treatment effects . CONCLUSIONS A modest beneficial effect of atorvastatin on eGFR , particularly in those with albuminuria , was observed . Atorvastatin did not influence albuminuria incidence . Atorvastatin was effective at decreasing CVD in those with and without a moderately decreased eGFR and achieved a high absolute benefit STUDY OBJECTIVE To examine the effect of atorvastatin on cognitive function by testing two hypotheses : that atorvastatin 10 mg/day would impair cognitive function , and that other biochemical and demographic measures would better predict cognitive performance than atorvastatin alone . DESIGN R and omized , double-blind , placebo-controlled study . SETTING Two primary acute care setting s in the north and northwest of Tasmania , Australia . PATIENTS Fifty-seven patients from the Lipid Lowering and Onset of Renal Disease ( LORD ) trial . INTERVENTION Participants were r and omly assigned to receive either atorvastatin 10 mg/day or matching placebo . Cognitive testing was performed in two sessions occurring 12 weeks apart and involved three repeated measures of attention and concentration . MEASUREMENTS AND MAIN RESULTS Performance was measured using three st and ard neuropsychological tests : Digit Symbol Coding subtest , Trail Making Test , and Stroop Color-Word Reading Test . Patients received atorvastatin for a mean of 72.93 weeks and placebo for a mean of 68.85 weeks . Repeated- measures multivariate analysis of variance failed to identify any significant differences between the two groups on any of the three cognitive measures . Multiple regression analyses identified no single factor or combination of plasma cholesterol levels , renal function , liver function , or age that predicted cognitive performance in either the atorvastatin or placebo group on the three measures at either testing session . CONCLUSION Atorvastatin 10 mg/day did not produce decrements to cognitive performance . In addition , biochemical and demographic measures and the receipt of atorvastatin versus placebo did not individually or in combination predict cognitive performance on measures of attention and concentration The Sc and inavian Simvastatin Survival Study ( 4S ) was a double‐blind . r and omized placebo‐controlled multi‐centre clinical trial of long‐term Simvastatin therapy in patients with coronary heart disease who had total cholesterol levels between 5.5 and 8.0 mmol/1 , comprising 4444 patients , equally distributed to a Simvastatin and a placebo group . Patients achieved a significant 30 % relative reduction in overall mortality with Simvastatin therapy through a 42 % relative reduction in coronary heart disease mortality . Lp(a ) lipoprotein levels in Sc and inavian coronary heart disease patients were strikingly higher than in healthy controls . Numbers of deaths in the Simvastatin group differed significantly between quartiles of Lp(a ) lipoprotein levels , the reduction in deaths being most pronounced in the second ( next to lowest ) quartile . Subjects with major coronary events had significantly higher Lp(a ) lipoprotein levels than subjects without such events , in all groups . The relationship between Lp(a ) lipoprotein level and total mortality as well as between Lp(a ) lipoprotein level and major coronary events was significantly different from zero , in logistic regression analyses . The findings show that Lp(a ) lipoprotein predicts major coronary events as well as death in secondary prevention with Simvastatin . This prospect i ve study provides independent confirmation that a high Lp(a ) lipoprotein level is a significant coronary heart disease risk factor Background Results of the Air Force/Texas Coronary Atherosclerosis Prevention Study ( AFCAPS/TexCAPS ) demonstrated that treatment with lovastatin , in addition to modifications of diet and lifestyle , reduced the rate of first acute major coronary events compared with placebo in a cohort that included participants with average to mildly elevated total levels of cholesterol , and below average levels of high-density lipoprotein cholesterol , women , and elderly subjects . Objective To describe the baseline characteristics of the study 's cohort . Design This was a double-blind , placebo-controlled , primary -prevention trial in which Americans with average to mildly elevated total levels of cholesterol [ 4.65–6.83 mmol/l ( 180–264 mg/dl ) ] and no clinical evidence of atherosclerotic cardiovascular disease were r and omly allocated either 20–40 mg/day lovastatin or placebo in addition to a low-saturated fat , low-cholesterol diet . Baseline characteristics of the study cohort are described , and the characteristics of a USA reference population based upon NHANES III data are provided for comparison . Results The study includes 5608 men ( 85 % ) and 997 women ( 15 % ) with mean total cholesterol level 5.71 ± 0.54 mmol/l ( 221 ± 21 mg/dl ) , low-density lipoprotein cholesterol level 3.88 ± 0.44 mmol/l ( 150 ± 17 mg/dl ) , high-density lipoprotein cholesterol 0.96 ± 0.15 mmol/l ( 37 ± 6 mg/dl ) , and median triglyceride level 1.78 ± 0.86 mmol/l ( 158 ± 76 mg/dl ) . The mean age is 58 years ( ranges 45–73 years for men and 55–73 years for women ) . The participants are 89 % white , 7 % Hispanic , and 3 % black . Conclusion Results from AFCAPS/TexCAPS will be applicable to large segments of population s ; in the USA alone , eight million share the demographic and baseline-lipid-level characteristics of the study cohort There is experimental evidence to suggest that hypercholesterolaemia may play a pathogenetic role in progressive glomerular injury . We investigated the effect of cholesterol-lowering therapy on the progression of diabetic nephropathy in 34 patients with non-insulin-dependent diabetes mellitus . Patients were r and omly assigned in a single-blind fashion to treatment with either lovastatin , an HMG CoA reductase inhibitor ( n = 16 ; mean dose 30.0 + /- 12.6 mg/day ) or placebo ( n = 18 ) for 2 years . Renal function was assessed by serially measuring the serum creatinine , glomerular filtration rate ( using Cr51-EDTA ) , and 24-h urinary protein excretion . Lovastatin treatment was associated with significant reductions in total cholesterol ( p < 0.001 ) , LDL-cholesterol ( p < 0.001 ) and apo B ( p < 0.01 ) , the reductions at 24 months being 26 , 30 and 18 % , respectively . Beneficial effects on serum triglyceride , HDL-cholesterol and apo A1 levels were also observed . Lp(a ) showed no significant change in both groups . Glomerular filtration rate deteriorated significantly in the placebo group after 24 months ( p < 0.025 ) but showed no significant change in the lovastatin-treated patients . The increase in serum creatinine was statistically significant ( p < 0.02 ) in placebo-treated patients at 12 and 24 months , and in the lovastatin group after 24 months . Twenty-four hour urinary protein excretion increased in both groups ( p < 0.05 ) . Lovastatin treatment was not associated with significant elevations in liver or muscle enzymes . We conclude that effective normalisation of hypercholesterolaemia may retard the progression of diabetic nephropathy BACKGROUND Evaluating the effects of decreasing low-density lipoprotein ( LDL ) cholesterol levels requires large r and omized trials . In preparation for such a trial , we assessed the biochemical efficacy , safety , and tolerability of adding ezetimibe , 10 mg/d , to simvastatin , 20 mg/d , as initial therapy for such patients . METHODS Two hundred three patients ( 152 predialysis patients with creatinine levels > or = 1.7 mg/dL [ > or = 150 micromol/L ] , 18 patients on peritoneal dialysis therapy , and 33 patients on hemodialysis therapy ) were r and omly assigned to the administration of simvastatin , 20 mg/d , plus ezetimibe , 10 mg/d ; or simvastatin , 20 mg , plus placebo ezetimibe daily . RESULTS After 6 months , allocation to simvastatin monotherapy was associated with a 31-mg/dL ( 0.8-mmol/L ) decrease in nonfasting LDL cholesterol levels compared with baseline . Allocation to simvastatin plus ezetimibe produced an additional 18-mg/dL ( 0.47-mmol/L ) decrease in LDL cholesterol level , representing an incremental 21 % reduction over that achieved with simvastatin monotherapy ( P < 0.0001 ) . There were no statistically significant effects of the addition of ezetimibe to simvastatin on triglyceride or high-density lipoprotein cholesterol levels . Ezetimibe was not associated with an excess risk of abnormal liver function test results or of elevated creatine kinase levels and did not impair absorption of fat-soluble vitamins . There were no serious adverse events caused by study treatment . CONCLUSION This 6-month study shows that the addition of ezetimibe to simvastatin , 20 mg/d , as initial therapy for patients with chronic kidney disease was well tolerated and produced an additional 21 % decrease in LDL cholesterol levels . The clinical efficacy and safety of combination therapy in this population are now being assessed in a large r and omized trial G of the National Cholesterol Education Program ( NCEP ) and other national and international organizations are now placing increased emphasis on the importance of effective reduction of cholesterol , in particular low-density lipoprotein ( LDL ) cholesterol , in patients with coronary artery disease (CAD).1,2 These recommendations are based on overwhelming evidence from epidemiologic studies and clinical trials.3–9 More recent studies have led to the suggestion that additional clinical benefit may be gained by lowering LDL cholesterol beyond currently recommended levels . The Post-Coronary Artery Bypass Graft trial demonstrated that in patients who had undergone bypass grafts , there was significantly less progression of atherosclerosis with an aggressive approach to LDL cholesterol reduction ( to a mean LDL cholesterol of 93 to 97 mg/dl [ 2.4 to 2.5 mmol/L ] ) compared with a moderate treatment strategy ( mean LDL cholesterol level of 132 to 136 mg/dl [ 3.4 to 3.5 mmol/L]).10 In the Atorvastatin Versus Revascularization Treatments study , patients with stable CAD were r and omized to receive atorvastatin 80 mg/day or angioplasty and /or usual medical care.11 The 36 % relative reduction in risk of ischemic events showed a trend toward significance and was associated with an LDL cholesterol level of 77 mg/dl ( 1.99 mmol/L ) compared with 119 mg/dl ( 2.08 mmol/L ) in the angioplasty/usual-care group . • • • The Aggressive Lipid Lowering Initiation Abates New Cardiac Events ( ALLIANCE ) trial is an ongoing 4-year , population -based , r and omized , open-label study of aggressive lipid lowering with atorvastatin compared with a usual medical care regimen in a managed healthcare setting . Atorvastatin has been shown to reduce LDL cholesterol by 41 % to 61 % over the 10to 80-mg/day dose range.12 Furthermore , in head-to-head evaluations , treatment with atorvastatin 10 to 40 mg/day has demonstrated significantly greater reductions in LDL cholesterol than milligramequivalent doses of simvastatin , pravastatin , fluvastatin , and lovastatin.13 The primary objective of ALLIANCE is to test the hypothesis that aggressive treatment of LDL cholesterol to beyond levels currently recommended in NCEP guidelines can provide incremental benefit in terms of reducing the incidence of major coronary events in patients with existing CAD . Men and women aged 18 to 75 years with a history of CAD were identified from relevant managed healthcare organization ( MHCO ) data bases . CAD was defined as 1 of the following : acute myocardial infa rct ion ( .3 months before screening ) , percutaneous transluminal coronary artery angioplasty ( .6 months before screening ) , and coronary artery bypass graft surgery or unstable angina ( .3 months before screening ) . Patients with chronic stable angina and patients awaiting revascularization procedures were not enrolled in the study . Major exclusion criteria were : breastfeeding or pregnancy ; women of childbearing age who planned to become pregnant during the study ; women who did not practice a method of birth control considered acceptable to the investigator ; any significant abnormalities the investigator believed may compromise the patient ’s safety or successful completion of the study ; any disease process likely to limit life to less than the duration of the study ; all cancers ( excluding basal cell and squamous cell skin cancers ) ; New York Heart Association class III or IV congestive heart failure ; and known hypersensitivities to hydroxymethylglutaryl coenzyme A reductase inhibitors . Informed consent was obtained from the study From the Metabolic and Atherosclerosis Research Center , Cincinnati , Ohio ; Chicago Center for Clinical Research , Chicago , Illinois ; Departments of Medicine and Pharmacology , University of Minnesota , Minneapolis , Minnesota ; and Parke-Davis Pharmaceutical Research , Ann Arbor , Michigan . This study is being sponsored by Parke-Davis Pharmaceutical Research , a Division of Warner Lambert Company , Ann Arbor , Michigan ; and Pfizer Inc. , New York , New York . Mr. Singer ’s address is : Parke-Davis Pharmaceutical Research , 2800 Plymouth Road , Ann Arbor , Michigan 48105 . Manuscript received August 16 , 1999 ; revised manuscript received and accepted February 2 , 2000 . TABLE I Cardiovascular Although diabetes is a major cause of chronic kidney disease ( CKD ) , limited data describe the cardiovascular benefit of hydroxymethyl glutaryl CoA reductase inhibitors ( statins ) in people with both of these conditions . This study sought to determine whether pravastatin reduced the incidence of first or recurrent cardiovascular events in people with non-dialysis-dependent CKD and concomitant diabetes , using data from three r and omized trials of pravastatin 40 mg daily versus placebo . CKD was defined by estimated GFR < 60 or 60 to 89.9 ml/min per 1.73 m2 with proteinuria . Of 19,737 patients , 4099 ( 20.8 % ) had CKD but not diabetes at baseline , 873 ( 4.4 % ) had diabetes but not CKD , and 571 ( 2.9 % ) had both conditions . The primary composite outcome was time to myocardial infa rct ion , coronary death , or percutaneous/surgical coronary revascularization . Median follow-up was 64 mo . After adjustment for trial and r and om treatment assignment , the incidence of the primary outcome was lowest in individuals with neither CKD nor diabetes ( 15.2 % ) , intermediate in individuals with only CKD ( 18.6 % ) or only diabetes ( 21.3 % ) , and highest in individuals with both characteristics ( 27.0 % ) . Pravastatin reduced the relative likelihood of the primary outcome to a similar extent in subgroups defined by the presence or absence of CKD and diabetes . For example , pravastatin was associated with a significant reduction in the relative risk of the primary outcome by 25 % in patients with CKD and concomitant diabetes and by 24 % in individuals with neither characteristic . However , the absolute reduction in the risk of the primary outcome as a result of pravastatin use was highest in patients with both CKD and diabetes ( 6.4 % ) and lowest in individuals with neither characteristic ( 3.5 % ) . In conclusion , stage 2 or early stage 3 CKD and diabetes both are associated with higher cardiovascular risk , and pravastatin reduces cardiovascular event rates in people with neither , one , or both characteristics . Given the high absolute benefit of pravastatin in patient with diabetes and stage 2 or early stage 3 CKD , this population in particular should be targeted for widespread use of statins . Additional studies are needed to determine whether these benefits apply to patients with more severe CKD , and recruitment to such studies should be given high priority BACKGROUND Chronic kidney disease is associated with higher levels of inflammatory biomarkers . Statins have anti-inflammatory properties and may attenuate loss of kidney function . Although inflammation may mediate progressive renal injury , the relation between statin use , markers of inflammation , and the rate of kidney function loss has not been eluci date d. We examined the association between pravastatin use , levels of C-reactive protein ( CRP ) , soluble tumor necrosis factor receptor II ( sTNFrii ) , and the rate of kidney function loss . METHODS We performed a post hoc analysis of data from a r and omized placebo controlled trial of pravastatin 40 mg daily in people with previous myocardial infa rct ion . Glomerular filtration rate ( GFR ) was estimated using the Modification of Diet in Renal Disease Study ( MDRD ) GFR equation . We studied 687 subjects with chronic kidney disease ( GFR < 60 mL/min/1.73 m(2 ) ) who did not experience a cardiovascular event during follow-up . Multivariate linear regression was used to study the relation between baseline CRP and sTNFrii and the rate of kidney function loss in mL/min/1.73 m(2)/year . Cross-product interaction terms were used to determine if these relations varied with pravastatin use . RESULTS Median baseline GFR was 54.5 mL/min/1.73 m(2 ) ( interquartile range 49.7 , 57.8 ) and median duration of follow-up was 58 months . Higher baseline CRP level was independently associated with more rapid kidney function loss ( highest tertile 0.6 mL/min/1.73 m(2 ) per year faster than lowest tertile ) ( P= 0.001 ) . A similar independent relation was observed between tertile of sTNFrii and rate of kidney function loss ( highest tertile 0.5 mL/min/1.73 m(2 ) per year faster than lowest tertile ) ( P= 0.006 ) . Subjects with both CRP and sTNFrii in the highest tertile ( " inflamed " status ) appeared to derive more renal benefit from pravastatin than those without ( P for interaction 0.047 ) . In these 108 subjects , renal function loss in pravastatin recipients was 0.8 mL/min/1.73 m(2)/year slower than placebo ( 95 % CI 0 to 1.5 mL/min/1.73 m(2)/year slower ) ( P= 0.039 ) . CONCLUSION Higher CRP and sTNFrii are independently associated with faster rates of kidney function loss in chronic kidney disease . Pravastatin appears to prevent loss of kidney function to a greater extent in individuals with greater evidence of inflammation , although this was of borderline significance . These data suggest that inflammation may mediate the loss of kidney function among subjects with chronic kidney disease and concomitant coronary disease CONTEXT Blood pressure control ( < 140/90 mm Hg ) rates for hypertension fall far short of the US national goal of 50 % or more . Achievable control rates in varied practice setting s and geographic regions and factors that predict improved blood pressure control are not well identified . OBJECTIVE To determine the success and predictors of blood pressure control in a large hypertension trial involving a multiethnic population in diverse practice setting s. DESIGN The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial is a r and omized , double-blind , active-controlled clinical trial with a mean follow-up of 4.9 years . Participant enrollment began in February 1994 and follow-up was completed in March 2002 . SETTING A total of 623 centers in the United States , Canada , and the Caribbean . PARTICIPANTS A total of 33,357 participants ( aged > or = 55 years ) with hypertension and at least one other coronary heart disease risk factor . INTERVENTIONS Participants were r and omly assigned to receive ( double-blind ) chlorthalidone , 12.5 - 25 mg/d ( n=15,255 ) , amlodipine 2.5 - 10 mg/d ( n=9048 ) , or lisinopril 10 - 40 mg/d ( n=9054 ) after other medication was discontinued . Doses were increased within these ranges and additional drugs from other classes were added as needed to achieve blood pressure control ( < 140/90 mm Hg ) . MAIN OUTCOME MEASURES The outcome measures for this report are systolic and diastolic blood pressure , the proportion of participants achieving blood pressure control ( < 140/90 mm Hg ) , and the number of drugs required to achieve control in all three groups combined . RESULTS Mean age was 67 years , 47 % were women , 35 % black , 36 % diabetic ; 90 % were on antihypertensive drug treatment at entry . At the first of two pre-r and omization visits , blood pressure was < 140/90 mm Hg in only 27.4 % of participants . After 5 years of follow-up , the percent controlled improved to 66 % . Systolic blood pressure was < 140 mm Hg in 67 % of participants , diastolic blood pressure was < 90 mm Hg in 92 % , the mean number of drugs prescribed was 2.0+/-1.0 , and the percent on > or = 2 drugs was 63 % . Blood pressure control varied by geographic regions , practice setting s , and demographic and clinical characteristics of participants . CONCLUSIONS These data demonstrate that blood pressure may be controlled in two thirds of a multiethnic hypertensive population in diverse practice setting s. Systolic blood pressure is more difficult to control than diastolic blood pressure , and at least two antihypertensive medications are required for most patients to achieve blood pressure control . It is likely that the majority of people with hypertension could achieve a blood pressure < 140/90 mm Hg with the antihypertensive medications available today OBJECTIVE To study the long-term effects of simvastatin on urinary albumin excretion rate ( AER ) in normotensive microalbuminuric type 2 diabetic patients with hypercholesterolemia . RESEARCH DESIGN AND METHODS A total of 19 normotensive microalbuminuric hypercholesterolemic type 2 diabetic patients entered a double-blind crossover study for 2 years , receiving either simvastatin ( 20 mg/day ) or placebo ( each treatment for 1 year ) . RESULTS Simvastatin significantly decreased plasma cholesterol ( total and LDL ) after 52 weeks of treatment . A concomitant significant decrease of AER ( 25 % from basal ) with no significant changes in creatinine clearance was observed during the same period . CONCLUSIONS Our data are in keeping with the hypothesis that simvastatin might be used as an additional means to preserve renal function in microalbuminuric hypercholesterolemic type 2 diabetic patients Context Previously published results of this r and omized , double-blind trial showed that hypertensive patients treated with doxazosin rather than chlorthalidone more often developed heart failure . Did differences in blood pressure control or treatment with other drugs explain these findings ? Contribution This analysis shows that the slightly worse blood pressure control achieved with doxazosin did not explain higher risks for heart failure . Risks with doxazosin versus chlorthalidone were highest among patients who received monotherapy ( relative risk , 3.10 ) and lowest among patients who received stepped care with additional drugs ( relative risk , 1.42 ) . Implication s Increased risks for heart failure with doxazosin versus chlorthalidone are attenuated but not eliminated when additional antihypertensive drugs are used . The Editors The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial ( ALLHAT ) , a r and omized , double-blind , multicenter clinical trial including 42 418 participants at 623 clinical sites , is design ed to determine whether treatment begun with a calcium-channel blocker ( amlodipine ) , an angiotensin-converting enzyme inhibitor ( lisinopril ) , or an -adrenergic blocker ( doxazosin ) compared to treatment with a diuretic ( chlorthalidone ) reduces the incidence of fatal coronary heart disease or nonfatal myocardial infa rct ion in high-risk patients with hypertension ( 1 ) . Secondary end points are all-cause mortality , stroke , and other cardiovascular events . A lipid-lowering trial in a subset of 10 356 participants is design ed to determine whether decreasing cholesterol levels with a hydroxymethyl glutamyl coenzyme A reductase inhibitor ( pravastatin ) compared with usual care reduces all-cause mortality in older , moderately hypercholesterolemic patients . In January 2000 , the doxazosin arm of the trial was discontinued ( 2 ) because major cardiovascular disease ( relative risk , 1.25 [ 95 % CI , 1.17 to 1.33 ] ; P < 0.001 ) , especially heart failure ( relative risk , 2.04 [ 95 % CI , 1.79 to 2.32 ] ; P < 0.001 ) , was significantly increased compared with the chlorthalidone arm . Equally important , a low probability existed that doxazosin would show benefit over chlorthalidone for the primary end point by the scheduled study end , given the lack of difference ( relative risk , 1.02 [ 95 % CI , 0.90 to 1.17 ] ; P > 0.2 ] at that time . These intention-to-treat analyses compared patients assigned to chlorthalidone with patients assigned to doxazosin . In this article , we analyze how treatment changes may have affected the comparison of doxazosin with chlorthalidone in terms of heart failure . Our major objectives are to ascertain to what extent the relative risk with doxazosin versus chlorthalidone depends on 1 ) whether the assigned drugs were used as monotherapy or in combination with other agents and 2 ) the difference in decreases in systolic and diastolic blood pressure . Methods Study Design The rationale and design of ALLHAT are described in detail elsewhere ( 1 ) . In brief , eligible participants were men and women 55 years of age or older who had systolic or diastolic hypertension ( 140/90 mm Hg or hypertension controlled with medication ) plus at least one additional risk factor for coronary heart disease events . The risk factors included previous ( > 6 months ) myocardial infa rct ion or stroke , left ventricular hypertrophy on electrocardiography or echocardiography , history of type 2 diabetes , current cigarette smoking , and a low high-density lipoprotein cholesterol level . Persons with a history of hospitalized or treated symptomatic heart failure or a known ejection fraction less than 0.35 were excluded . Unless the drug regimen required tapering for safety , participants who had been taking antihypertensive medications continued to do so until the day of r and omization , at which point they stopped taking all previous medications . On the day after r and omization , treatment with the study drug was initiated . Enrollment occurred from February 1994 through January 1998 . The original reported number of 42 448 participants and 625 sites changed because 30 patients with poor documentation of informed consent were excluded ( 2 ) . Participants were assigned by a computer-generated r and omization schedule in a ratio of 1.7:1 to receive chlorthalidone or doxazosin . R and omization was stratified by center and blocked over time to maintain the ratio . All participants gave written informed consent , and all centers obtained institutional review board approval . Ascertainment of Outcomes At each clinic visit , occurrence of study end points was assessed by the clinical investigator . A hospital discharge summary was required for each hospitalized study outcome , and a death certificate was required for each death . ALLHAT defined symptomatic heart failure as clear-cut signs or symptoms of left or right ventricular dysfunction that can not be attributed to other causes . A patient had to have at least one symptom ( paroxysmal nocturnal dyspnea , dyspnea at rest , New York Heart Association class III dyspnea or other symptoms [ on less than ordinary exertion ] , or orthopnea ) and one sign ( rales , ankle edema , tachycardia , cardiomegaly or characteristic pulmonary pattern on chest radiography , S3 gallop , or jugular venous distention ) ( 3 ) . Symptoms and signs were determined by the clinic investigator through patient history , chart review , or consultation with the treating physician , but such data were not collected central ly . A one-time sample of 24 hospitalized or fatal heart failure events was review ed in a blinded manner by the ALLHAT Endpoints Subcommittee ; 20 of 24 ( 83 % ) were deemed to have complete data for a definitive diagnosis . Of the 20 cases , the agreement rate between the subcommittee and the clinic investigators was 90 % ( 18 of 20 ) and similar in both treatment groups . Details on the validity of diagnosis of heart failure will be provided in a future report . Measurement and Treatment of Blood Pressure The ALLHAT protocol specified a stepped-care treatment program for hypertension . Trained observers using st and ardized techniques measured blood pressures during the trial ( 1 , 2 ) . All blood pressures were calculated as the average of two measurements obtained with a 30-second interval between them . The blood pressure goal in all four study arms was less than 140/90 mm Hg . This level was to be achieved with the lowest possible dose of blinded first-line drug , with addition of second- and third-line open-label therapy as needed after reaching the maximal dose of first-line drug . Chlorthalidone and doxazosin were to be taken once daily in the morning . By design , doses were selected to achieve equivalent blood pressure control in the treatment groups . The first , second , and third dosage levels were 12.5 mg/d , 12.5 mg/d ( sham titration ) , and 25 mg/d , respectively , for chlorthalidone and 2 mg/d , 4 mg/d , and 8 mg/d for doxazosin . Double-blinded 1-mg and 12.5-mg doses of doxazosin and chlorthalidone , respectively , were used for the first week to minimize the frequency of postural hypotension associated with doxazosin . The identity of drugs was masked at each dosage level , but dosage level was not . After r and omization , patients were seen for dose titration as needed at 1 and 3 months per the protocol , but they could return more often until target blood pressure was reached . Subsequently , required visits occurred at 3-month intervals during the first year and at 4-month intervals thereafter . Open-label second-step drugs were added as needed and tolerated . These agents were reserpine ( 0.05 to 0.2 mg/d ) , clonidine ( 0.1 to 0.3 mg twice daily ) , and atenolol ( 25 to 100 mg/d ) . The choice of second-step drug was at the discretion of the treating clinician-investigator . The third-step agent was hydralazine ( 25 to 100 mg twice daily ) . Details of these therapies are provided elsewhere ( 1 ) . Investigators could choose to prescribe open-label antihypertensive drugs other than those provided by the study . However , use of the drug classes under study thiazide diuretics , calcium antagonists , angiotensin-converting enzyme inhibitors , and -adrenergic blockerswas strongly discouraged to avoid dilution of treatment comparisons . When clinical conditions other than uncontrolled hypertension ( for example , angina or heart failure ) were present , drugs from any study class could be used . If a step 1 drug was specifically required for blood pressure control while blinded drug treatment was continued , the step 1 drug could be added as open-label therapy but the dose could not exceed one half the maximum recommended by the Fifth Joint National Committee ( 4 ) . In most such cases , unblinding the patient or the investigator to treatment assignment was not necessary . ( Overall , < 1 % of drug identities were provided to either participant or investigator . ) Any of nine possible open-label drug typesdiuretic , calcium-channel blocker , angiotensin-converting enzyme inhibitor , -adrenergic blocker , atenolol , reserpine , clonidine , hydralazine , and other antihypertensive drug ( which could include nonatenolol -blockers , although drug name was not logged)could be recorded at each visit . Because diuretics , angiotensin-converting enzyme inhibitors , and -blockers are beneficial in preventing or treating heart failure , we call these antihypertensive heart failure drugs . Data on antihypertensive drug use before study enrollment were collected , but not by drug class . Statistical Analysis Data were analyzed for use of additional drugs according to participants ' r and omized treatment assignments and regardless of continuation of blinded study treatment . The outcomes all heart failure ( treated outside hospital , hospitalized , or fatal ) and hospitalized or fatal heart failure were examined by treatment group for the entire cohort . The time to event for the previously published as-r and omized analyses was the interval from r and omization to first diagnosis of heart failure for patients who had an outcome , or from r and omization to BACKGROUND Elevated blood glucose levels are reported with thiazide-type diuretic treatment of hypertension . The significance of this finding is uncertain . Our objectives were to compare the effect of first-step antihypertensive drug therapy with thiazide-type diuretic , calcium-channel blocker , or angiotensin-converting enzyme inhibitor on fasting glucose ( FG ) levels and to determine cardiovascular and renal disease risks associated with elevated FG levels and incident diabetes mellitus ( DM ) in 3 treatment groups . METHODS We performed post hoc subgroup analyses from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) among nondiabetic participants who were r and omized to receive treatment with chlorthalidone ( n = 8419 ) , amlodipine ( n = 4958 ) , or lisinopril ( n = 5034 ) and observed for a mean of 4.9 years . RESULTS Mean FG levels increased during follow-up in all treatment groups . At year 2 , those r and omized to the chlorthalidone group had the greatest increase ( + 8.5 mg/dL [ 0.47 mmol/L ] vs + 5.5 mg/dL [ 0.31 mmol/L ] for amlodipine and + 3.5 mg/dL [ 0.19 mmol/L ] for lisinopril ) . The odds ratios for developing DM with lisinopril ( 0.55 [ 95 % confidence interval , 0.43 - 0.70 ] ) or amlodipine ( 0.73 [ 95 % confidence interval , 0.58 - 0.91 ] ) vs chlorthalidone at 2 years were significantly lower than 1.0 ( P<.01 ) . There was no significant association of FG level change at 2 years with subsequent coronary heart disease , stroke , cardiovascular disease , total mortality , or end-stage renal disease . There was no significant association of incident DM at 2 years with clinical outcomes , except for coronary heart disease ( risk ratio , 1.64 ; P = .006 ) , but the risk ratio was lower and nonsignificant in the chlorthalidone group ( risk ratio , 1.46 ; P = .14 ) . CONCLUSIONS Fasting glucose levels increase in older adults with hypertension regardless of treatment type . For those taking chlorthalidone vs other medications , the risk of developing FG levels higher than 125 mg/dL ( 6.9 mmol/L ) is modestly greater , but there is no conclusive or consistent evidence that this diuretic-associated increase in DM risk increases the risk of clinical events Although substantial evidence suggests that treatment of dyslipidemia with statins reduces mortality and morbidity that are associated with cardiovascular disease , only a few studies have examined the efficacy of statins on inflammatory and fibrinolytic status in patients with chronic kidney disease ( CKD ) . A 6-mo , prospect i ve , r and omized study was design ed to assess the efficacy of atorvastatin in reducing circulating inflammatory and fibrinolytic parameters in patients with CKD . Sixty-six patients with CKD ( stages 2 , 3 , and 4 ) and LDL cholesterol levels > or = 100 mg/dl were r and omly assigned ( 2:1 ) to receive 20 mg/d atorvastatin ( n = 44 ) or nonatorvastatin therapy ( n = 22 ) . Lipid profile , renal function , fibrinolytic balance ( tissue plasminogen activator [ t-PA ] and plasminogen activator inhibitor-1 ) , and inflammatory markers ( C-reactive protein [ CRP ] , IL-1 beta , IL-6 , and TNF-alpha ) were measured before and 6 mo after atorvastatin was added to the treatment . Twenty-five age-matched individuals with normal renal function ( estimated GFR > 90 ml/min ) were used as healthy control subjects . Patients with CKD had higher CRP , IL-1 beta , TNF-alpha , and IL-6 levels than age-matched population with normal renal function . t-PA concentration was higher in patients with CKD ( P = 0.000 ) . Plasminogen activator inhibitor-1 values were comparable in all patients . Total cholesterol and LDL cholesterol were significantly reduced only in patients who received atorvastatin . In addition to the hypolipidemic effect , atorvastatin treatment significantly reduced inflammatory parameters : CRP ( median 4.1 to 2.9 ; P = 0.015 ) , TNF-alpha ( 6.0 + /- 2.7 to 4.7 + /- 2.4 ; P = 0.046 ) , and IL-1 beta levels ( 1.9 + /- 0.7 to 1.2 + /- 0.7 ; P = 0.001 ) . These parameters remained unchanged in patients who were not treated with atorvastatin . Fibrinolytic parameters were not modified by atorvastatin treatment . Patients with CKD showed higher levels of inflammatory parameters and t-PA levels than age-matched healthy control subjects . Atorvastatin treatment , in addition to its beneficial effect on cholesterol levels , improved the inflammatory state of these patients without modifying fibrinolytic balance Inflammation is an important factor in the development and progression of atherosclerosis . Observational studies have suggested that renin-angiotensin system inhibition might lower C-reactive protein ( CRP ) . The aim of this study was to test the hypothesis that angiotensin-converting enzyme inhibition with fosinopril would reduce inflammation in a placebo-controlled trial involving 621 subjects . CRP was determined using a high-sensitivity assay at baseline and after 3 months of fosinopril treatment . The median CRP level at baseline was 1.38 mg/dl ( interquartile range 0.64 to 2.86 ) and did not significantly differ between treatment groups . CRP levels at baseline were significantly associated with future cardiovascular events , even after adjustment for age and gender ( odds ratio 1.76 , 95 % confidence interval 1.16 to 2.67 , p = 0.008 ) . Fosinopril treatment during 3 months did not result in a significantly higher reduction of CRP levels compared with placebo ( difference -0.11 , p = 0.20 ) . Exploratory analysis suggested an interaction between gender and fosinopril treatment on CRP reduction ( p = 0.07 ) . Male gender was associated with a significantly larger reduction in CRP compared to female gender . In conclusion , contrary to previous observational studies , no effect of angiotensin-converting enzyme inhibition on CRP levels was found AIM To describe baseline characteristics of patients in the Collaborative AtoRvastatin Diabetes Study ( CARDS ) , a r and omized , placebo-controlled trial of lipid lowering with atorvastatin 10 mg daily for the primary prevention of major cardiovascular events in patients with Type 2 diabetes . METHODS The main eligibility criteria were Type 2 diabetes , age 40 - 75 years , no previous history of coronary heart disease , stroke or other major cardiovascular events , a documented history of at least one of retinopathy , micro- or macroalbuminuria , hypertension or current smoking , LDL-cholesterol < or = 4.14 mmol/l and triglycerides < or = 6.78 mmol/l . RESULTS R and omization of 2838 persons ( 909 women ) into CARDS was completed in June 2001 . At entry , mean age was 62 years , 12 % were over 70 years old and median duration of diabetes was 6 years . Median fasting lipid levels were total cholesterol 5.4 mmol/l , LDL-cholesterol 3.1 mmol/l , HDL-cholesterol 1.4 mmol/l and triglyceride 1.7 mmol/l . There was a documented history of retinopathy in 30 % of patients , micro/macroalbuminuria in 11 % ( additionally 17 % had micro/macroalbuminuria based on two elevated pretreatment measurements of albumin-creatinine ratios ) , hypertension in 79 % and 23 % were current smokers . CONCLUSION CARDS will contribute importantly to the evidence for the macrovascular and microvascular benefits of lipid lowering with atorvastatin in patients with Type 2 diabetes . The results are likely to have important implication s for the management of patients This study presents the long-term safety data from AFCAPS/TexCAPS , the first primary prevention trial to demonstrate that men and women with average levels of low-density lipoprotein cholesterol ( LDL-C ) and below average levels of high-density lipoprotein cholesterol ( HDL-C ) can significantly benefit from long-term treatment to lower LDL-C ; lovastatin 20 to 40 mg/day reduced the risk of a first acute major coronary event ( fatal or nonfatal myocardial infa rct ion , unstable angina , or sudden death ) by 37 % ( p = 0.00008 ) . This double-blind r and omized , placebo-controlled trial , in 6,605 generally healthy middle-aged and older men and women , had prespecified end point and cancer analyses . All analyses were intention-to-treat . Safety monitoring included history , physical examination , and laboratory studies ( including hepatic transaminases and creatine phosphokinase [ CPK ] ) . All participants , even those who discontinued treatment , were contacted annually for vital status , cardiovascular events , and cancer history . After an average of 5.2 years of follow-up , there were 157 deaths ( 80 receiving lovastatin and 77 receiving placebo ; relative risk [ RR ] 1.04 ; 95 % confidence interval [ CI ] 0.76 to 1.42 ; p = 0.82 ) ; of which 115 were noncardiovascular ( RR 1.21 ; CI 0.84 to 1.74 ; p = 0.31 ) , and of these , 82 were due to cancer ( RR 1.41 ; CI 0.91 to 2.19 ; p = 0.13 ) . There were no significant differences between treatment groups in overall cancer rates , discontinuations for noncardiovascular adverse experiences , or clinical ly important elevations of hepatic transaminases or CPK . Among those who used cytochrome P450 isoform ( CYP3A4 ) inhibitors , there were no treatment group differences in the frequency of clinical ly important muscle-related adverse events . Treatment with lovastatin 20 to 40 mg daily for primary prevention of coronary heart disease was well tolerated and reduced the risk of first acute coronary events without increasing the risk of either noncardiovascular mortality or cancer The Incremental Decrease in End Points through Aggressive Lipid Lowering ( IDEAL ) study is an investigator-initiated trial design ed to determine whether additional clinical benefit might be gained through a strategy that decreases levels of low-density lipoprotein cholesterol levels better than those currently achieved with established statin therapy in patients who have coronary heart disease . IDEAL is a multicenter prospect i ve , r and omized , open-label , blinded , end point classification study . Patients who had myocardial infa rct ion were r and omized to prescription treatment with 80 mg/day of atorvastatin or 20 mg/day of simvastatin ( the dose was increased to 40 mg/day at week 24 in those patients whose plasma total cholesterol remained > 5.0 mmol/L , or 190 mg/dl , or whose low-density lipoprotein cholesterol remained > 3.0 mmol/L , or 115 mg/dl ) . The primary clinical outcome variable is the time to initial occurrence of a major coronary event , which is defined as nonfatal acute myocardial infa rct ion , coronary death , or resuscitated cardiac arrest . The study is design ed to have a power of 90 % to detect a relative decrease of 20 % in the atorvastatin-group compared with the simvastatin-group in the number of major events caused by coronary heart disease over approximately 5.5 years . The 8,888 r and omized patients had the following characteristics : mean age 61.7 + /- 9.5 years , 19.1 % women ( mean age 64.0 + /- 9.5 years ) , baseline total cholesterol 5.1 + /- 1.0 mmol/L ( 197 mg/dl ) , low-density lipoprotein cholesterol 3.2 + /- 0.9 mmol/L ( 124 mg/dl ) , and high-density lipoprotein cholesterol 1.2 + /- 0.3 mmol/L ( 46 mg/dl ) . Drug treatment before r and omization consisted of statins in 77 % of patients , aspirin in 78.9 % , beta blockers in 75.1 % , and angiotensin-converting enzyme inhibitors in 30 % Background and Purpose — Elevated urinary albumin excretion ( UAE ) is associated with an increased carotid intima-media thickness ( IMT ) . Because angiotensin-converting enzyme inhibitors as well as statins have been shown to lower UAE and the progression of IMT , we assessed the effects of fosinopril and pravastatin on carotid IMT in subjects with an increased UAE ( 15 to 300 mg/24 h ) . Methods — IMT was measured at the posterior wall of the left common carotid artery using radio-frequency signal analysis obtained by M-mode ultrasonography . 642 subjects were double-blind r and omized to fosinopril 20 mg or matching placebo and to pravastatin 40 mg or matching placebo and were available for intention-to-treat analysis . Results — Mean age was 51±11 years , 65 % were male , the median UAE was 22.5 ( 15.5 to 40.8 ) mg/24 h , and the mean IMT at baseline was 0.77±0.18 mm . The overall progression rate of IMT in 4 years was 0.037±0.006 mm . No significant difference in IMT progression was found between fosinopril , pravastatin , or matching placebo . IMT after 4 years was predicted by IMT at baseline , age , gender , pulse pressure , and low-density lipoprotein cholesterol levels . Furthermore , a higher incidence of clinical events was observed in subjects with an IMT > 1 mm after a mean follow-up of 46±7 months ( hazard ratio , 3.13 ; 95 % confidence interval , 1.59 to 6.16 ; P=0.001 ) . Conclusions — In subjects with an increased UAE , treatment with fosinopril and pravastatin showed no significant effect on carotid IMT . Furthermore , an IMT < 1 mm at baseline is an important indicator for event-free survival OBJECTIVE Impaired endothelium-dependent vasodilation represents an early manifestation of atherosclerosis . Prospect i ve studies have demonstrated that impaired endothelial function in the peripheral circulation of hypercholesterolemic patients predicts CV events and can be restored by statin treatment . Whether this also holds true in the renal circulation has not yet been adequately addressed . METHODS In a double-blind , r and omized , placebo-controlled cross-over trial , 40 hypercholesterolemic patients were r and omly assigned to receive rosuvastatin ( 10mg/day ) and matching placebo . The primary objective of the study was to assess the effect of 6-week treatment with rosuvastatin on basal NOS activity of the renal vasculature , as assessed by measuring renal plasma flow ( RPF ) both before and after blockade of NOS with systemic infusion of N(G)-monomethyl-L-arginine ( L-NMMA ) . In a subgroup of 20 patients we also studied the effects of a 3-day treatment regimen . RESULTS Compared to placebo treatment , rosuvastatin decreased LDL-cholesterol levels both after 3 days and 6 weeks of treatment . The decrease in RPF in response to L-NMMA was significantly more pronounced after 6-week therapy with rosuvastatin compared to placebo ( -13.7+/-1.0 % versus -11.3+/-0.7 % ; p=0.046 ) , indicating increased basal NOS activity with rosuvastatin treatment . A trend towards improved basal NOS activity was already evident after 3-day treatment . CONCLUSION Treatment with rosuvastatin improved basal NOS activity in the renal circulation of hypercholesterolemic patients , suggestive of a nephroprotective effect . In view of the close relation between altered renal function and cardiovascular events , these nephroprotective effects may contribute to the improved CV prognosis associated with statin treatment Objectives : Small dense low-density lipoprotein ( LDL ) plays an important role in glomerular injury through conversion to an oxidatively modified form of LDL . However , few studies have evaluated the effects of antilipidemic agents on the LDL particle size and renal function in hyperlipidemic patients with nondiabetic nephropathy . Methods : This study was a r and omized crossover trial comparing the effects of atorvastatin ( 10 mg/day ) and probucol ( 500 mg/day ) administered for 24 weeks in 31 patients ( urinary albumin excretion 0.3–2.0 g/day and creatinine clearance > 30 mL/min/1.73 m2 ) . Lipid parameters , mean LDL particle diameter , creatinine clearance , and urinary albumin to creatinine excretion ratio were measured before and during treatment periods . Main findings : Atorvastatin and probucol significantly reduced the serum total cholesterol and LDL cholesterol concentrations . When stratified by mean baseline LDL particle size at 25.5 nm , atorvastatin increased ( p < 0.05 ) LDL particle size from 24.6 ± 0.5 to 25.2 ± 0.9 nm only in the < 25.5 nm ( pattern B ) group , whereas probucol decreased ( p < 0.05 ) LDL size from 24.8 ± 0.9 to 24.2 ± 0.9 nm in the pattern B group and from 25.9 ± 0.5 to 24.6 ± 0.8 nm in the ≥25.5 nm ( pattern A ) group . No significant differences in urinary albumin/creatinine excretion ratio and creatinine clearance were observed in both groups during treatment . Conclusions : Only atorvastatin improved the LDL-subtype distribution in hyperlipidemic patients with nondiabetic nephropathy , although both agents exhibited no renoprotective action , suggesting that the effects on LDL-subtype distribution do not directly lead to renoprotection Of 17 patients with idiopathic membranous nephropathy ( IMN ) and nephrotic syndrome , 9 were allocated to treatment with simvastatin ( an HMG CoA-reductase inhibitor ) and low cholesterol diet , and 8 to diet alone . At entry , the treatment and control groups did not differ in mean serum creatinines , chromium-labelled EDTA clearances , urinary protein/creatinine ratios , serum albumins , and lipid profiles . The mean follow up period ( + /- SEM ) in the treated group was 19.3 ( + /- 4.4 ) months compared with 16.6 ( + /- 5.9 ) months in the control group . At the end of the trial the fall in chromium-labelled EDTA clearances was similar ( -1.27 versus -1.28 mls/min/months/1.73 m2 ) in the treatment and control groups respectively . The mean ( + /- SEM ) total and LDL-cholesterol had gone from 10.5 ( + /- 0.94 ) and 8.02 ( + /- 1 ) mmol/l to 5.2 ( + /- 0.49 ) and 3.47 ( + /- 0.44 ) respectively in the treated patients . Additionally the mean ( + /- SEM ) albumin and urinary protein/creatinine ratio went from 25.6 ( + /- 2.4 ) gm/l and 0.52 ( + /- 0.09 ) gm/mmol to 45.5 ( + /- 2.8 ) and 0.13 ( + /- 0.04 ) respectively . There was little change in total and LDL-cholesterol ; albumin and urinary protein/creatinine ratio in the control group . This study supports the observation that lowering serum cholesterol in the nephrotic syndrome reduces proteinuria and increases serum albumin levels . No difference in the rate of decline in renal function could be demonstrated The effect of statin therapy on subclasses of LDL , VLDL and HDL lipoproteins is unclear . We compared changes in serum lipids , apolipoproteins and nuclear magnetic resonance ( NMR ) spectroscopy measured lipoprotein subclass concentration and average particle size over a minimum 6 months treatment period of atorvastatin 10 mg vs. placebo in 122 men and women . All subjects had type 2 diabetes and a modest dyslipidaemia ( mean LDL-cholesterol 3.2 mmol/l and median triglycerides 1.8 mmol/l ) and had a previous myocardial infa rct ion . Compared with placebo , atorvastatin therapy was associated with a greater decrease in medium VLDL ( median within person change -13.4 vs. -5.9 nmol/l , P<0.001 adjusted for baseline level ) , small VLDL ( median change -17.8 vs. -8.1 nmol/l , P=0.002 ) , large LDL ( mean within person change -167.9 vs. -48.6 nmol/l , P<0.001 ) and medium LDL ( median within person change -101.8 vs. -22.3 nmol/l , P=0.017 ) . Atorvastatin therapy was also associated with a greater increase in large HDL than placebo ( median change 1.40 vs. 0.80 micromol/l , P=0.02 ) and there was little change in small HDL so that average HDL particle size increased significantly with atorvastatin ( P=0.04 ) . In addition to reducing levels of ( enzymatically measured ) triglyceride , LDL-cholesterol and apolipoprotein B in diabetic patients , atorvastatin significantly reduces NMR measured medium and small VLDL and large and medium LDL , and increases large HDL The Treating to New Targets ( TNT ) trial is a parallel-group study that has r and omized 10,003 patients from 14 countries to double-blind treatment with either atorvastatin 10 or 80 mg . During the double-blind period , low-density lipoprotein ( LDL ) cholesterol levels are expected to reach approximate mean values of 100 mg/dl ( 2.6 mmol/L ) for the low-dose atorvastatin group and 75 mg/dl ( 1.9 mmol/L ) for the high-dose group . R and omized patients are expected to be followed for an average of 5 years . The primary end point is the time to occurrence of a major cardiovascular event , defined as coronary heart disease death , nonfatal myocardial infa rct ion , resuscitated cardiac arrest , or stroke . The large patient numbers in the TNT study and long follow-up should ensure that there is adequate power to definitively determine if reducing LDL cholesterol levels to approximately 75 mg/dl ( 1.9 mmol/L ) can provide additional clinical benefit BACKGROUND Statin therapy reduces the rates of heart attack , stroke , and revascularisation among a wide range of individuals . Reliable assessment of its cost-effectiveness in different circumstances is needed . METHODS 20,536 adults ( aged 40 - 80 years ) with vascular disease or diabetes were r and omly allocated 40 mg simvastatin daily ( 10,269 ) or placebo ( 10,267 ) for an average of 5 years . Comparisons were made of hospitalisation and statin costs ( 2001 UK prices ) during the scheduled treatment period between all simvastatin-allocated versus all placebo-allocated participants . Cost-effectiveness was estimated among different categories of participant . FINDINGS Allocation to simvastatin was associated with a highly significant 22 % ( 95 % CI 16 - 27 ; p<0.0001 ) proportional reduction in hospitalisation costs for all vascular events , with similar proportional reductions in every subcategory of participant studied . During an average of 5 years , estimated absolute reductions in vascular event costs per person allocated 40 mg simvastatin daily ranged from UK 847 pounds sterling ( SE 137 ) in the highest risk quintile studied to 264 pounds sterling ( 48 ) in the lowest . Mean excess cost of statin therapy among participants allocated simvastatin was 1497 pounds sterling ( 8) , with similar absolute increases in every subcategory . Costs of preventing a major vascular event with 40 mg simvastatin daily ranged from 4500 pounds sterling ( 95 % CI 2300 - 7400 ) among participants with a 42 % 5-year major vascular event rate to 31,100 pounds sterling ( 22,900 - 42,500 ) among those with a 12 % rate ( corresponding to 5-year major coronary event rates of 22 % and 4 % , respectively ) . INTERPRETATION Statin therapy is cost effective for a wider range of individuals with vascular disease or diabetes than previously recognised ( particularly with lower-priced generics ) . It would be appropriate to consider reducing the estimated level of vascular event risk at which statin therapy is recommended BACKGROUND Cardiovascular morbidity is a major burden in patients with type 2 diabetes . In the Steno-2 Study , we compared the effect of a targeted , intensified , multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria . METHODS The primary end point of this open , parallel trial was a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , nonfatal stroke , revascularization , and amputation . Eighty patients were r and omly assigned to receive conventional treatment in accordance with national guidelines and 80 to receive intensive treatment , with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia , hypertension , dyslipidemia , and microalbuminuria , along with secondary prevention of cardiovascular disease with aspirin . RESULTS The mean age of the patients was 55.1 years , and the mean follow-up was 7.8 years . The decline in glycosylated hemoglobin values , systolic and diastolic blood pressure , serum cholesterol and triglyceride levels measured after an overnight fast , and urinary albumin excretion rate were all significantly greater in the intensive-therapy group than in the conventional-therapy group . Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease ( hazard ratio , 0.47 ; 95 percent confidence interval , 0.24 to 0.73 ) , nephropathy ( hazard ratio , 0.39 ; 95 percent confidence interval , 0.17 to 0.87 ) , retinopathy ( hazard ratio , 0.42 ; 95 percent confidence interval , 0.21 to 0.86 ) , and autonomic neuropathy ( hazard ratio , 0.37 ; 95 percent confidence interval , 0.18 to 0.79 ) . CONCLUSIONS A target-driven , long-term , intensified intervention aim ed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent BACKGROUND Although angiotensin receptor antagonists and 3-hydroxy-3-methylgultaryl coenzyme A ( HMG-CoA ) reductase inhibitors ( statins ) have been shown to attenuate proteinuria individually , it remains unclear whether proteinuria may be additionally improved by statin therapy in well-controlled hypertensive patients treated with angiotensin receptor antagonists-based regimen and whether withdrawal of chronic statin treatment may abrogate this beneficial effect in normolipidemic patients . METHODS A total of consecutive 82 proteinuric patients treated with antihypertensive agents , including losartan , were r and omized 10 mg of pravastatin or placebo with a 6-month treatment . After completing 6 months of drug treatment , the pravastatin-treated patients were r and omly assigned to continue ( N= 19 ) or withdraw ( N= 17 ) pravastatin for a further 6 months . RESULTS Subjects treated with pravastatin had significant further improvement of proteinuria at 6 months compared with placebo group ( 559 + /- 251 mg/24 hours vs. 1262 + /- 557 mg/24 hours ) ( P < 0.0001 ) . Of 17 patients assigned to withdraw pravastatin , proteinuria returned to the pretreatment levels and was significantly higher than those who continued treatment . Multivariate analysis revealed that proteinuric improvement was significantly correlated with the continuous statin use . Urinary excretion of endothelin-1 ( ET-1 ) is decreased in pravastatin-treated patients , but withdrawal of statin result ed in 27 % up-regulation . The linear regression models in the initial statin-treated group showed that changes in urinary ET-1 correlated with urinary protein excretion ( r= 0.83 , P < 0.0001 ) . CONCLUSION We conclude that pravastatin administration is associated with improved proteinuria probably by inhibiting urine ET-1 levels in patients with losartan-based treatment . However , statin withdrawal abrogates this beneficial effect in patients initially responsive to this therapy OBJECTIVE To assess in diabetic patients with coronary heart disease ( CHD ) the effect of cholesterol lowering with simvastatin on mortality and the risk of CHD and other atherosclerotic events . RESEARCH DESIGN AND METHODS A post hoc subgroup analysis was carried out on data from 202 diabetic patients and 4,242 nondiabetic patients with previous myocardial infa rct ion or angina pectoris , serum total cholesterol 5.5–8.0 mmol/l , and serum triglycerides ≤ 2.5 mmol/l who were participating in the Sc and inavian Simvastatin Survival Study ( 4S ) . Participants in the 4S were r and omly assigned to double-blind treatment with simvastatin , 20 mg daily , with blinded dosage titration up to 40 mg daily , according to cholesterol response during the first 6–18 weeks , or placebo . Endpoints were 1 ) total mortality , 2 ) major CHD events ( CHD death or nonfatal myocardial infa rct ion ) , 3 ) other acute atherosclerotic events , 4 ) myocardial revascularization procedures . RESULTS Over the 5.4-year median follow-up period , simvastatin treatment produced mean changes in serum lipids in diabetic patients similar to those observed in nondiabetic patients . The relative risks ( RRs ) of main endpoints in simvastatin-treated diabetic patients were as follows : total mortality 0.57 ( 95 % CI , 0.30–1.08 ; P = 0.087 ) , major CHD events 0.45 ( 95 % CI , 0.27–0.74 ; P = 0.002 ) , and any atherosclerotic event 0.63 ( 95 % CI , 0.43–0.92 ; P = 0.018 ) . The corresponding RRs in nondiabetic patients were the following : 0.71 ( 95 % CI , 0.58–0.87 ; P = 0.001 ) , 0.68 ( 95 % CI , 0.60–0.77 ; P < 0.0001 ) , and 0.74 ( 95 % CI , 0.68–0.82 ; P < 0.0001 ) . CONCLUSIONS The results strongly suggest that cholesterol lowering with simvastatin improves the prognosis of diabetic patients with CHD . The absolute clinical benefit achieved by cholesterol lowering may be greater in diabetic than in nondiabetic patients with CHD because diabetic patients have a higher absolute risk of recurrent CHD events and other atherosclerotic events Renal insufficiency is frequently associated with both quantitative and qualitative abnormalities in lipid and hemorheologic profiles . Although this may lead to increased risk of cardiovascular disease , a number of studies have also shown dyslipidemia to be a significant risk factor for the progression of renal insufficiency in human chronic renal disease . This double-blind , placebo-controlled trial aim ed to assess the effect of fluvastatin , a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor , on these parameters in dyslipidemic patients with or without chronic renal insufficiency . After a 6-week placebo run-in , 42 patients who had been previously stratified into 2 groups on the basis of creatinine clearance levels ( 0.5 - 1.0 mL/sec or > 1.0 - 1.5 mL/sec ) were r and omized to treatment with fluvastatin ( 40 mg daily ) or matching placebo . Significant differences ( on analysis of variance with repeated measures ) were seen between fluvastatin and placebo treatment groups for changes in total cholesterol ( -15 % vs 1 % , respectively ; p < 0.001 ) , low density lipoprotein cholesterol ( LDL-C ; -21 % vs -5 % ; p < 0.001 ) , very low density lipoprotein cholesterol ( -14 % vs 14 % ; p = 0.017 ) , very low density lipoprotein triglycerides ( -1 % vs 29 % ; p = 0.014 ) and total triglycerides ( -7 % vs 24 % ; p < 0.001 ) . These effects on cholesterol levels were reflected in a significant decrease in apolipoprotein B levels with fluvastatin therapy ( p < 0.001 ) . Apolipoprotein A-I levels increased ( p = 0.054 ) despite no significant change in the levels of high density lipoprotein cholesterol . Response to therapy did not differ between the 2 renal function groups for any of the lipid , lipoprotein , and apolipoprotein variables . Hemorheologic parameters were not altered with fluvastatin therapy , regardless of renal function . ( ABSTRACT TRUNCATED AT 250 WORDS According to the concept of apolipoprotein (apo)-defined lipoproteins , apoA-I-containing lipoproteins consist of two subclasses referred to as lipoprotein A-I ( LpA-I ) and lipoprotein A-I : A-II ( LpA-I : A-II ) , and apoB-containing lipoproteins of five subclasses , namely lipoprotein B ( LpB ) , lipoprotein B : C ( LpB : C ) , lipoprotein B : E ( LpB : E ) , lipoprotein B : C : E ( LpB : C : E ) , and lipoprotein A-II : B : C : D : E ( LpA-II : B : C : D : E ) . The purpose of this study was to determine the levels of apoA-I- and apoB-containing lipoprotein subclasses before and after fluvastatin treatment of patients with chronic renal insufficiency . ApoA-I- and apoB-containing lipoprotein subclasses were measured in 15 patients with chronic renal failure and 15 asymptomatic subjects . The effect of fluvastatin on lipoprotein subclasses was determined in a r and omized , double-blind , placebo-controlled , two-way , treatment period crossover study . Patients were administered fluvastatin 40 mg/day or placebo during 8 weeks in a r and omized order . Patients were characterized by significantly higher levels of LpB ( P < 0.001 ) , LpB : C ( P < 0.001 ) , and LpB : E ( P < 0.05 ) , and slightly higher levels of LpB : C : E and LpA-II : B : C : D : E than controls . The levels of LpA-I : A-II were significantly lower ( P < 0.01 ) in patients than controls . Fluvastatin treatment reduced all apoB-containing subclasses , but only the reduced level of LpB subclass was statistically significant ( P < 0.02 ) . The levels of LpA-I and LpA-I : A-II were not affected . Fluvastatin treatment reduced and normalized LpB and LpB : E subclasses . Although slightly reduced , the levels of markedly atherogenic LpB : C subclass were not normalized . The potential role of LpB : C on the progression of coronary artery disease in chronic renal insufficiency remains to be determined in future studies BACKGROUND Chronic kidney disease ( CKD ) is associated with an increased incidence of cardiovascular disease ( CVD ) . The Anti-oxidant Therapy In Chronic Renal Insufficiency ( ATIC ) Study showed that a multistep treatment strategy improved carotid intima-media thickness , endothelial function , and microalbuminuria in patients with stages 2 to 4 CKD . Increased plasma concentrations of asymmetric dimethylarginine ( ADMA ) , an endogenous inhibitor of nitric oxide synthase , have been linked to greater CVD risk in patients with CKD . The aim of this study is to assess effects of the multistep intervention on plasma ADMA concentrations in the ATIC Study . STUDY DESIGN Secondary analysis of a r and omized double-blind placebo-controlled trial . SETTING & PARTICIPANTS 93 patients with creatinine clearance of 15 to 70 mL/min/1.73 m(2 ) ( according to the Cockcroft-Gault equation ) from 7 outpatient clinics in Amsterdam , The Netherl and s. INTERVENTION The treatment group received sequential treatment consisting of pravastatin , 40 mg/d . After 6 months , vitamin E , 300 mg/d , was added , and after another 6 months , homocysteine-lowering therapy ( folic acid , 5 mg/d ; pyridoxine , 100 mg/d ; and vitamin B(12 ) , 1 mg/d , all in 1 tablet ) were added and continued for another year . The control group received matching placebos . OUTCOME & MEASURES Plasma ADMA levels . RESULTS 36 participants ( 77 % ) in the treatment group and 38 ( 83 % ) in the placebo group completed the study . Mean ADMA and symmetric dimethylarginine concentrations in the total study population were 0.53 + /- 0.07 ( SD ) and 1.14 + /- 0.46 mumol/L , respectively . After 24 months , there was no overall effect of the treatment strategy on ADMA concentrations ( beta = -0.006 ; P = 0.27 ) . Analysis of separate treatment effects suggested that vitamin E significantly decreased ADMA levels by 4 % in the treatment group compared with the placebo group ( multiple adjusted P = 0.02 ) . LIMITATIONS The study was a secondary analysis , power calculation was based on the primary end point of carotid intima-media thickness , mean plasma ADMA levels were relatively low . CONCLUSION Overall , a multistep treatment strategy consisting of pravastatin , vitamin E , and B vitamins had no effect on plasma ADMA levels in a stage 2 to 4 CKD population . This suggests that the beneficial effects of the intervention were not mediated by changes in ADMA levels . Possible ADMA-lowering effects of vitamin E deserve further attention CONTEXT Studies have demonstrated that statins administered to individuals with risk factors for coronary heart disease ( CHD ) reduce CHD events . However , many of these studies were too small to assess all-cause mortality or outcomes in important subgroups . OBJECTIVE To determine whether pravastatin compared with usual care reduces all-cause mortality in older , moderately hypercholesterolemic , hypertensive participants with at least 1 additional CHD risk factor . DESIGN AND SETTING Multicenter ( 513 primarily community-based North American clinical centers ) , r and omized , nonblinded trial conducted from 1994 through March 2002 in a subset of participants from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) . PARTICIPANTS Ambulatory persons ( n = 10 355 ) , aged 55 years or older , with low-density lipoprotein cholesterol ( LDL-C ) of 120 to 189 mg/dL ( 100 to 129 mg/dL if known CHD ) and triglycerides lower than 350 mg/dL , were r and omized to pravastatin ( n = 5170 ) or to usual care ( n = 5185 ) . Baseline mean total cholesterol was 224 mg/dL ; LDL-C , 146 mg/dL ; high-density lipoprotein cholesterol , 48 mg/dL ; and triglycerides , 152 mg/dL. Mean age was 66 years , 49 % were women , 38 % black and 23 % Hispanic , 14 % had a history of CHD , and 35 % had type 2 diabetes . INTERVENTION Pravastatin , 40 mg/d , vs usual care . MAIN OUTCOME MEASURES The primary outcome was all-cause mortality , with follow-up for up to 8 years . Secondary outcomes included nonfatal myocardial infa rct ion or fatal CHD ( CHD events ) combined , cause-specific mortality , and cancer . RESULTS Mean follow-up was 4.8 years . During the trial , 32 % of usual care participants with and 29 % without CHD started taking lipid-lowering drugs . At year 4 , total cholesterol levels were reduced by 17 % with pravastatin vs 8 % with usual care ; among the r and om sample who had LDL-C levels assessed , levels were reduced by 28 % with pravastatin vs 11 % with usual care . All-cause mortality was similar for the 2 groups ( relative risk [ RR ] , 0.99 ; 95 % confidence interval [ CI ] , 0.89 - 1.11 ; P = .88 ) , with 6-year mortality rates of 14.9 % for pravastatin vs 15.3 % with usual care . CHD event rates were not significantly different between the groups ( RR , 0.91 ; 95 % CI , 0.79 - 1.04 ; P = .16 ) , with 6-year CHD event rates of 9.3 % for pravastatin and 10.4 % for usual care . CONCLUSIONS Pravastatin did not reduce either all-cause mortality or CHD significantly when compared with usual care in older participants with well-controlled hypertension and moderately elevated LDL-C. The results may be due to the modest differential in total cholesterol ( 9.6 % ) and LDL-C ( 16.7 % ) between pravastatin and usual care compared with prior statin trials supporting cardiovascular disease prevention OBJECTIVES The aim of this post hoc analysis from the TNT ( Treating to New Targets ) trial is to determine whether patients with previous coronary artery bypass grafting ( CABG ) surgery achieved clinical benefit from intensive low-density lipoprotein (LDL)-cholesterol lowering . BACKGROUND The development and progression of atherosclerosis is accelerated in coronary venous bypass grafts . METHODS A total of 10,001 patients with documented coronary disease , including 4,654 with previous CABG , were r and omized to atorvastatin 80 or 10 mg/day and were followed for a median of 4.9 years . The primary end point was the occurrence of a first major cardiovascular event ( cardiac death , nonfatal myocardial infa rct ion , resuscitated cardiac arrest , or stroke ) . RESULTS A first major cardiovascular event occurred in 11.4 % of the patients with prior CABG and 8.5 % of those without prior CABG ( p < 0.001 ) . In CABG patients , mean LDL-cholesterol levels at study end were 79 mg/dl in the 80-mg arm and 101 mg/dl in the 10-mg arm , and the primary event rate was 9.7 % in the 80-mg arm and 13.0 % in the 10-mg arm ( hazard ratio 0.73 , 95 % confidence interval 0.62 to 0.87 , p = 0.0004 ) . Repeat revascularization during follow-up , either CABG or percutaneous coronary intervention , was performed in 11.3 % of the CABG patients in the 80-mg arm and 15.9 % in the 10-mg arm ( hazard ratio 0.70 , 95 % confidence interval 0.60 to 0.82 , p < 0.0001 ) . CONCLUSIONS Intensive LDL-cholesterol lowering to a mean of 79 mg/dl with atorvastatin 80 mg/day in patients with previous CABG reduces major cardiovascular events by 27 % and the need for repeat coronary revascularization by 30 % , compared with less intensive cholesterol-lowering to a mean of 101 mg/dl with atorvastatin 10 mg/day . ( A Study to Determine the Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target Levels [ TNT ] ; NCT00327691 ) BACKGROUND Lower blood cholesterol concentrations have consistently been found to be strongly associated with lower risks of coronary disease but not with lower risks of stroke . Despite this observation , previous r and omised trials had indicated that cholesterol-lowering statin therapy reduces the risk of stroke , but large-scale prospect i ve confirmation has been needed . METHODS 3280 adults with cerebrovascular disease , and an additional 17256 with other occlusive arterial disease or diabetes , were r and omly allocated 40 mg simvastatin daily or matching placebo . Subgroup analyses were prespecified of first " major vascular event " ( ie , non-fatal myocardial infa rct ion or coronary death , stroke of any type , or any revascularisation procedure ) in prior disease subcategories . Subsidiary outcomes included any stroke , and stroke sub-type . Comparisons are of all simvastatin-allocated versus all placebo-allocated participants ( ie , " intention-to-treat " ) , which yielded an average difference in LDL cholesterol of 1.0 mmol/L ( 39 mg/dL ) during the 5-year treatment period . FINDINGS Overall , there was a highly significant 25 % ( 95 % CI 15 - 34 ) proportional reduction in the first event rate for stroke ( 444 [ 4.3 % ] simvastatin vs 585 [ 5.7 % ] placebo ; p<0.0001 ) , reflecting a definite 28 % ( 19 - 37 ) reduction in presumed ischaemic strokes ( p<0.0001 ) and no apparent difference in strokes attributed to haemorrhage ( 51 [ 0.5 % ] vs 53 [ 0.5 % ] ; rate ratio 0.95 [ 0.65 - 1.40 ] ; p=0.8 ) . In addition , simvastatin reduced the numbers having transient cerebral ischaemic attacks alone ( 2.0 % vs 2.4 % ; p=0.02 ) or requiring carotid endarterectomy or angioplasty ( 0.4 % vs 0.8 % ; p=0.0003 ) . The reduction in stroke was not significant during the first year , but was already significant ( p=0.0004 ) by the end of the second year . Among patients with pre-existing cerebrovascular disease there was no apparent reduction in the stroke rate , but there was a highly significant 20 % ( 8 - 29 ) reduction in the rate of any major vascular event ( 406 [ 24.7 % ] vs 488 [ 29.8 % ] ; p=0.001 ) . The proportional reductions in stroke were about one-quarter in each of the other subcategories of participant studied , including : those with coronary disease or diabetes ; those aged under or over 70 years at entry ; and those presenting with different levels of blood pressure or lipids ( even when the pretreatment LDL cholesterol was below 3.0 mmol/L [ 116 mg/dL ] ) . INTERPRETATION Much larger numbers of people in the present study suffered a stroke than in any previous cholesterol-lowering trial . The results demonstrate that statin therapy rapidly reduces the incidence not only of coronary events but also of ischaemic strokes , with no apparent effect on cerebral haemorrhage , even among individuals who do not have high cholesterol concentrations . Allocation to 40 mg simvastatin daily reduced the rate of ischaemic strokes by about one-quarter and so , after making allowance for non-compliance in the trial , actual use of this regimen would probably reduce the stroke rate by about a third . HPS also provides definitive evidence that statin therapy is beneficial for people with pre-existing cerebrovascular disease , even if they do not already have manifest coronary disease OBJECTIVE The Sc and inavian Simvastatin Survival Study showed that simvastatin treatment reduced cardiovascular events in hypercholesterolemic subjects with coronary heart disease . The clinical benefits of therapy were similar in all three subgroups : normal fasting glucose ( NFG , n = 3,237 ) , impaired fasting glucose ( IFG , n = 678 ) , and diabetes ( n = 483 ) . This analysis compared the costs of simvastatin treatment with the costs of cardiovascular disease-related hospitalizations in the three subgroups . RESEARCH DESIGN AND METHODS The cost of simvastatin treatment was defined as the average retail price and the cost of drug safety monitoring and adverse experiences . The costs of cardiovascular disease-related hospitalizations were determined by actual rates of hospitalization and 1995 MEDSTAT diagnosis-related group costs . RESULTS Within trial , simvastatin treatment cost approximately $ 6,000 per patient . Simvastatin treatment reduced cardiovascular disease-related hospitalizations by 23 % in NFG ( P = 0.001 ) , 30 % in IFG ( P = 0.015 ) , and 40 % in diabetic subjects ( P = 0.007 ) within trial ( median follow-up of 5.4 years ) . Average length of stay was reduced by 2.4 days in diabetic subjects ( P = 0.021 ) . Total cardiovascular disease-related hospital days were reduced by 28 % ( P < 0.001 ) in NFG , 38 % ( P = 0.005 ) in IFG , and 55 % ( P < 0.001 ) in diabetic subjects . For NFG subjects , simvastatin reduced the average cost of cardiovascular disease-related hospitalizations by $ 3,585 , which offset 60 % of the cost of simvastatin therapy . For IFG subjects , average cardiovascular disease-related hospitalization costs were reduced by $ 4,478 , which offset 74 % of the drug cost . For diabetic subjects , there was a net cost savings of $ 1,801 per subject within trial . CONCLUSIONS Simvastatin significantly reduced cardiovascular disease-related hospitalizations and total hospital days for all three groups and significantly reduced length of stay for the diabetic group in addition to providing significant clinical benefits . The benefits were greatest in the diabetic group , with estimated cost savings within trial from simvastatin treatment The Air Force/Texas Coronary Atherosclerosis Prevention Study ( AFCAPS/TexCAPS ) is a r and omized , double-blind , placebo-controlled primary prevention trial . It is design ed to test the hypothesis that in addition to a lipid-lowering diet , treatment with lovastatin is more effective than placebo in reducing acute major coronary events ( i.e. , sudden cardiac death , fatal and nonfatal myocardial infa rct ion , and unstable angina ) in a cohort with normal to mildly elevated total ( 180 to 264 mg/dl ) and low-density lipoprotein ( LDL ) cholesterol ( 130 to 190 mg/dl ) and low high-density lipoprotein ( HDL ) cholesterol ( < or = 45 mg/dl for men and < or = 47 mg/dl for women ) . Two sites in Texas , Lackl and Air Force Base in San Antonio and the University of North Texas Health Science Center in Fort Worth , will conduct the study . After at least 12 weeks of an American Heart Association Step 1 diet and 2 weeks placebo run-in , 6,605 men and women , ages 45 to 73 and 55 to 73 years , respectively , without clinical evidence of coronary heart disease , are r and omized in equal numbers to either lovastatin ( 20 mg/day ) or placebo . Study procedures maintain the blind , allowing titration of lovastatin from 20 to 40 mg/day to achieve an LDL cholesterol goal of < or = 110 mg/dl . All participants are followed until study completion , when 320 participants have had a primary end point or a minimum of 5 years after the last participant is r and omized , whichever occurs last . All end points are adjudicated by an independent committee using prespecified criteria . Unique features of this trial are ( 1 ) the inclusion of unstable angina in the primary end point to reflect the increasing trend to treat coronary heart disease aggressively before a myocardial infa rct ion has occurred , ( 2 ) aggressive pharmacologic intervention , with titration , to attain an LDL cholesterol goal less than the current National Cholesterol Education Panel guidelines for primary prevention , and ( 3 ) a cohort that includes women , the elderly , and those with mild to moderate hyperlipidemia and low HDL cholesterol . Compared with earlier studies , results will be applicable to a broader population and may help clarify the role of aggressive LDL cholesterol reduction measures in primary prevention . Treatment of this population is likely to realize the greatest cumulative long-term benefit in the prevention of acute major coronary events BACKGROUND Lowering the blood cholesterol level may reduce the risk of coronary heart disease . This double-blind study was design ed to determine whether the administration of pravastatin to men with hypercholesterolemia and no history of myocardial infa rct ion reduced the combined incidence of nonfatal myocardial infa rct ion and death from coronary heart disease . METHODS We r and omly assigned 6595 men , 45 to 64 years of age , with a mean ( + /- SD ) plasma cholesterol level of 272 + /- 23 mg per deciliter ( 7.0 + /- 0.6 mmol per liter ) to receive pravastatin ( 40 mg each evening ) or placebo . The average follow-up period was 4.9 years . Medical records , electrocardiographic recordings , and the national death registry were used to determine the clinical end points . RESULTS Pravastatin lowered plasma cholesterol levels by 20 percent and low-density-lipoprotein cholesterol levels by 26 percent , whereas there was no change with placebo . There were 248 definite coronary events ( specified as nonfatal myocardial infa rct ion or death from coronary heart disease ) in the placebo group , and 174 in the pravastatin group ( relative reduction in risk with pravastatin , 31 percent ; 95 percent confidence interval , 17 to 43 percent ; P < 0.001 ) . There were similar reductions in the risk of definite nonfatal myocardial infa rct ions ( 31 percent reduction , P < 0.001 ) , death from coronary heart disease ( definite cases alone : 28 percent reduction , P = 0.13 ; definite plus suspected cases : 33 percent reduction , P = 0.042 ) , and death from all cardiovascular causes ( 32 percent reduction , P = 0.033 ) . There was no excess of deaths from noncardiovascular causes in the pravastatin group . We observed a 22 percent reduction in the risk of death from any cause in the pravastatin group ( 95 percent confidence interval , 0 to 40 percent ; P = 0.051 ) . CONCLUSIONS Treatment with pravastatin significantly reduced the incidence of myocardial infa rct ion and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infa rct ion Aims Type 1 diabetes mellitus patients with microalbuminuria have endothelial dysfunction associated with the degree of albuminuria but not with LDL‐cholesterol levels . Lipid‐lowering agents such as statins may still be of benefit as they can correct endothelial dysfunction by both lipid and non‐lipid mechanisms . We therefore examined the effects of atorvastatin on brachial artery endothelial dysfunction in these patients The purpose of this double-blind , r and omized , placebo-controlled trial was to determine the long-term effects of pravastatin and fosinopril treatment on peripheral endothelial function in subjects with albuminuria . Subjects ( mean age 51 years , 63 % male ) were r and omized to pravastatin 40 mg or matching placebo and to fosinopril 20 mg or matching placebo . Using high resolution ultrasound , flow-mediated dilation ( FMD ) and nitroglycerin-induced dilation ( NID ) was assessed at baseline and after 4 years of treatment in a total of 276 subjects . At baseline , mean+/-st and ard error FMD was 4.73+/-0.49 % and NID was 10.86+/-0.67 % . Pravastatin significantly reduced total cholesterol and LDL cholesterol ( p<0.01 ) and r and omization to pravastatin was associated with a non-significant improvement of 18.9 % in FMD ( + 0.80+/-0.95 , p=0.09 ) , without a significant change in NID . Interestingly , pravastatin significantly increased FMD by 34.9 % in men ( + 1.23 , p=0.04 ) , but only 1.1 % in women ( + 0.06 , p=0.95 ) . Fosinopril was not associated with a change in FMD or NID despite significantly decreasing urinary albumin excretion , systolic and diastolic blood pressure ( all p<0.01 ) . In conclusion , after 4 years of follow-up , pravastatin treatment tended to increase FMD and this effect was predominantly present in men . Fosinopril treatment did not modify FMD during long-term follow-up Chronic renal insufficiency is characterized by specific abnormalities in lipoprotein metabolism , affecting both apolipoprotein A ( apo A)- and apo B-containing lipoproteins . To evaluate the effects of fluvastatin , a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor , on renal dyslipoproteinemia , we performed a r and omized , double-blind , placebo-controlled , two-way , period cross-over study . Study patients were administered fluvastatin , 40 mg/d , or placebo during 8 weeks in r and omized order . Forty-five nonnephrotic patients ( 28 men , 17 women ) without diabetes with moderate to advanced chronic renal insufficiency participated in the study . Their mean age was 56.4 + /- 11.0 years . Glomerular filtration rate ranged from 12 to 44 mL/min/1.73 m2 of body surface area ( mean , 27.5 + /- 10.5 mL/min/1.73 m2 ) . Fluvastatin treatment result ed in significant reductions in the primary outcome variables low-density lipoprotein cholesterol ( LDL-C ; -26 % ; P < 0.001 ) , apo B ( -21 % ; P < 0.001 ) , and lipoprotein B complex ( Lp-Bc ) ( -14 % ; P < 0.01 ) . There were statistically significant differences between fluvastatin and placebo treatment for the secondary outcome variables total cholesterol ( -19 % ) , triglycerides ( TGs ; -13 % ) , VLDL-C ( -13 % ) , apo E ( -13 % ) , and Lp-B ( -22 % ) . There was no treatment effect on high-density lipoprotein cholesterol or lipoprotein(a ) . Fluvastatin treatment was well tolerated , with no serious adverse events during the study . In conclusion , fluvastatin treatment was well tolerated in patients with moderately advanced renal insufficiency and led to a significant reduction in cholesterol-rich , but to a lesser extent in TG-rich , apo B-containing lipoproteins . It remains to be clarified whether these positive changes in lipoprotein profile also will result in attenuation of the atherosclerotic process in these patients , as well as beneficially affect the progression of chronic renal failure BACKGROUND Inflammation and oxidative stress ( OS ) are risk factors for cardiovascular disease in chronic kidney disease ( CKD ) . This study assessed the acute effect of simvastatin on inflammatory and OS markers in stage 3 and 4 CKD patients . METHODS R and omized , placebo-controlled , double-blind , cross-over study comprising 66 patients who were r and omized to simvastatin ( 20 mg/day ) or placebo for two 8-week periods . Glomerular filtration rate ( GFR ) , lipid profile , C-reactive protein ( CRP ) , fibrinogen , carbonyls and total radical-trapping antioxidant potential ( TRAP ) were measured . Interactions between potential confounding factors , such as diabetes mellitus , malnutrition , drug use , hypercholesterolemia and treatment response were assessed through the course of inflammatory and OS levels . RESULTS Thirty-three patients were r and omized to simvastatin/placebo ( S-P ) , and 33 to placebo/simvastatin ( P-S ) . Simvastatin significantly reduced total and LDL cholesterol ( pretreatment vs. posttreatment : p=0.0001 and p=0.0001 , respectively ) in both periods . No differences were seen in CRP , fibrinogen , carbonyls and TRAP levels between S-P and P-S groups at the end of the 2 study periods . GFR was similar in both groups and negatively correlated to fibrinogen ( r=-0.25 , p=0.04 ) and TRAP ( r=-0.27 , p=0.03 ) . No interactions were found between confounding factors and response to simvastatin . There was no interference of either a period effect or any carryover effect on study results . CONCLUSIONS The use of simvastatin in CKD patients acutely did not reduce serum inflammation or OS markers . Possibly higher doses and /or longer treatment course of statin are required to produce drug pleiotropic effects in nondialysis CKD patients We carried out a r and omized trial of stepwise intensive treatment or st and ard treatment of risk factors in patients with type 2 diabetes and microalbuminuria . Patients were allocated st and ard treatment ( n = 80 ) or intensive treatment ( n = 80 ) . Intensive treatment was a stepwise implementation of behaviour modification , pharmacological therapy targeting hyperglycaemia , hypertension , dyslipidaemia , and microalbuminuria . The primary endpoint was development of nephropathy . Secondary endpoints were incidence or progression of diabetic retinopathy and neuropathy . Patients were followed for 3.8 years . The intensive group had significantly lower rates of progression to hephropathy ( odds ratio 0.27 [ 95 % CI 0.10 - 0.75 ] ) , progression of retinopathy ( 0.45 ( 0.21 - 0.95 ] ) , and progression of autonomic neuropathy ( 0.32 [ 0.12 - 0.78 ] ) . In conclusion , intensified multifactorial intervention in patients with type 2 diabetic mellitus and microalbuminuria has beneficial effects on long-term complications OBJECTIVE Although previous studies suggest that treatment of dyslipidemia with statins reduces mortality and morbidity that are associated with cardiovascular disease , only a few studies have examined the efficacy of statins on atherosclerotic status in patients with chronic kidney disease ( CKD ) . MATERIAL S AND METHODS A 12-month , prospect i ve , r and omized study was design ed to assess the efficacy of rosuvastatin in reducing circulating atherosclerotic parameters and renal function in patients with CKD . Thirty-eight patients with CKD and LDL cholesterol levels > or = 100 mg/dL were r and omly assigned to receive 2.5 mg/dL rosuvastatin ( group A , n=22 ) or nonrosuavastatin therapy ( group B , n=16 ) . Lipid profile , estimated glomerular filtration rate ( eGFR ) , high sensitivity C-reactive protein ( hs-CRP ) , and intima-media thickness ( IMT ) were measured before and 12 months after rosuvastatin was added to the treatment . RESULTS Total cholesterol , low-density lipoprotein cholesterol , remnant-like particle-cholesterol and triglycerides were significantly reduced only in patients who received rosuvastatin . These parameters remained unchanged in patients who were not treated with rosuvastatin . eGFR was significantly increased from 50.7+/-18.7 mL/min/1.73 m(2 ) to 53.3+/-20.1 mL/min/1.73 m(2 ) and a significant reduction of U-P was detected in group A patients ( 0.17+/-0.29 vs. 0.13+/-0.3 g/day ; p<0.01 ) . In addition to the hypolipidemic effect , rosuvastatin treatment significantly reduced hs-CRP ( p=0.0054 ) . Moreover , maximal IMT at the baseline ( 1.89+/-0.98 mm ) decreased significantly to 1.75+/-0.87 mm at 12 months ( p=0.0231 ) . CONCLUSION Rosuvastatin treatment , in addition to its beneficial effect on cholesterol levels , reduced maximal IMT and modified the inflammatory state of these patients Objective To determine the relative importance of recognised risk factors for non-haemorrhagic stroke , including serum cholesterol and the effect of cholesterol-lowering therapy , on the occurrence of non-haemorrhagic stroke in patients enrolled in the LIPID ( Long-term Intervention with Pravastatin in Ischaemic Disease ) study . Design The LIPID study was a placebo-controlled , double-blind trial of the efficacy on coronary heart disease mortality of pravastatin therapy over 6 years in 9014 patients with previous acute coronary syndromes and baseline total cholesterol of 4–7 mmol/l . Following identification of patients who had suffered non-haemorrhagic stroke , a pre-specified secondary end point , multivariate Cox regression was used to determine risk in the total population . Time-to-event analysis was used to determine the effect of pravastatin therapy on the rate of non-haemorrhagic stroke . Results There were 388 non-haemorrhagic strokes in 350 patients . Factors conferring risk of future non-haemorrhagic stroke were age , atrial fibrillation , prior stroke , diabetes , hypertension , systolic blood pressure , cigarette smoking , body mass index , male sex and creatinine clearance . Baseline lipids did not predict non-haemorrhagic stroke . Treatment with pravastatin reduced non-haemorrhagic stroke by 23 % ( P = 0.016 ) when considered alone , and 21 % ( P = 0.024 ) after adjustment for other risk factors . Conclusions The study confirmed the variety of risk factors for non-haemorrhagic stroke . From the risk predictors , a simple prognostic index was created for non-haemorrhagic stroke to identify a group of patients at high risk . Treatment with pravastatin result ed in significant additional benefit after allowance for risk factors BACKGROUND Renal dyslipoproteinemia is characterized by the accumulation of intact and partially metabolized triglyceride-rich lipoproteins . Reduced lipolytic enzyme activities may be one of the major pathophysiological mechanisms contributing to a retarded catabolism of these lipoproteins in patients with renal insufficiency . OBJECTIVE To evaluate the effect of gemfibrozil treatment on renal dyslipoproteinemia . STUDY DESIGN A r and omized , controlled open study with 2 parallel groups . OUTCOME VARIABLES Plasma concentrations of lipids , apolipoproteins and lipoprotein particles . PATIENTS AND METHODS Fifty-seven non-nephrotic , non-diabetic patients with moderately advanced renal insufficiency were r and omized to either treatment with gemfibrozil at dosages from 300 to 900 mg/day ( n = 28 ) or dietary counseling ( n = 29 ) . The intervention period was 12 months . Plasma concentrations of lipids , apolipoproteins and apoA- and apoB-containing lipoprotein particles were determined at the entry and after 6 and 12 months of treatment . RESULTS No serious adverse effects occurred during the study . Six patients experienced mild gastrointestinal symptoms and prematurely withdrew from the drug treatment . In the group treated with gemfibrozil the plasma concentrations of triglycerides , total cholesterol , very low density lipoprotein ( VLDL ) and low density ( LDL ) cholesterol decreased significantly by 47 , 13 , 43 and 14 % , respectively , in comparison to baseline . High density lipoprotein ( HDL ) cholesterol increased significantly by 18 % . ApoB , apoC-III , apoC-III in heparin-manganese precipitate ( reflecting apoC-III in VLDL and LDL ) and apoE decreased significantly by 21 , 18 , 26 and 49 % , respectively . Furthermore , gemfibrozil treatment result ed in the reduction of plasma concentrations of complex ( LP-Bc ) and simple ( LP-B ) apoB-containing lipoprotein particles by 22 and 7 % , respectively . However , these changes were not statistically significant . There was a slight , insignificant increase in the levels of LP-A-I : A-II particles and no change in the levels of LP-A-I particles . In contrast to the effect of the pharmacological intervention , the dietary counseling only result ed in minor changes in the plasma lipid and apolipoprotein profiles . The only significant changes were a 10 % increase in HDL cholesterol and a 35 % decrease in apoE. CONCLUSIONS Gemfibrozil treatment significantly reduces both plasma lipids and apoB , apoC-III and apoE concentrations in patients with moderately advanced renal insufficiency . The results of this study indicate that gemfibrozil enhances the clearance of apoB-containing triglyceride-rich lipoproteins BACKGROUND The Sc and inavian Simvastatin Survival Study ( 4S ) r and omized 4444 patients with coronary heart disease ( CHD ) and serum cholesterol 5.5 to 8.0 mmol/L ( 213 to 310 mg/dL ) with triglycerides < or = 2.5 mmol/L ( 220 mg/dL ) to simvastatin 20 to 40 mg or placebo once daily . Over the median follow-up period of 5.4 years , one or more major coronary events ( MCEs ) occurred in 622 ( 28 % ) of the 2223 patients in the placebo group and 431 ( 19 % ) of the 2221 patients in the simvastatin group ( 34 % risk reduction , P<.00001 ) . Simvastatin produced substantial changes in several lipoprotein components , which we have attempted to relate to the beneficial effects observed . METHODS AND RESULTS The Cox proportional hazards model was used to assess the relationship between lipid values ( baseline , year 1 , and percent change from baseline at year 1 ) and MCEs . The reduction in MCEs within the simvastatin group was highly correlated with on-treatment levels and changes from baseline in total and LDL cholesterol , apolipoprotein B , and less so with HDL cholesterol , but there was no clear relationship with triglycerides . We estimate that each additional 1 % reduction in LDL cholesterol reduces MCE risk by 1.7 % ( 95 % CI , 1.0 % to 2.4 % ; P<.00001 ) . CONCLUSIONS These analyses suggest that the beneficial effect of simvastatin in individual patients in 4S was determined mainly by the magnitude of the change in LDL cholesterol , and they are consistent with current guidelines that emphasize aggressive reduction of this lipid in CHD patients OBJECTIVES This sub analysis of the TNT ( Treating to New Targets ) study investigates the effects of intensive lipid lowering with atorvastatin in patients with coronary heart disease ( CHD ) with and without pre-existing chronic kidney disease ( CKD ) . BACKGROUND Cardiovascular disease is a major cause of morbidity and mortality in patients with CKD . METHODS A total of 10,001 patients with CHD were r and omized to double-blind therapy with atorvastatin 80 mg/day or 10 mg/day . Patients with CKD were identified at baseline on the basis of an estimated glomerular filtration rate ( eGFR ) < 60 ml/min/1.73 m(2 ) using the Modification of Diet in Renal Disease equation . The primary efficacy outcome was time to first major cardiovascular event . RESULTS Of 9,656 patients with complete renal data , 3,107 had CKD at baseline and demonstrated greater cardiovascular comorbidity than those with normal eGFR ( n = 6,549 ) . After a median follow-up of 5.0 years , 351 patients with CKD ( 11.3 % ) experienced a major cardiovascular event , compared with 561 patients with normal eGFR ( 8.6 % ) ( hazard ratio [ HR ] = 1.35 ; 95 % confidence interval [ CI ] 1.18 to 1.54 ; p < 0.0001 ) . Compared with atorvastatin 10 mg , atorvastatin 80 mg reduced the relative risk of major cardiovascular events by 32 % in patients with CKD ( HR = 0.68 ; 95 % CI 0.55 to 0.84 ; p = 0.0003 ) and 15 % in patients with normal eGFR ( HR = 0.85 ; 95 % CI 0.72 to 1.00 ; p = 0.049 ) . Both doses of atorvastatin were well tolerated in patients with CKD . CONCLUSIONS Aggressive lipid lowering with atorvastatin 80 mg was both safe and effective in reducing the excess of cardiovascular events in a high-risk population with CKD and CHD OBJECTIVES We evaluated the efficacy of statin therapy in primary prevention among individuals with moderate chronic kidney disease ( CKD ) . BACKGROUND Whether patents with moderate CKD ( estimated glomerular filtration rate [ eGFR ] < 60 ml/min/1.73 m(2 ) ) benefit from statin therapy is uncertain , particularly among those without hyperlipidemia or known cardiovascular disease . METHODS Within the JUPITER ( Justification for the Use of statins in Prevention-an Intervention Trial Evaluating Rosuvastatin ) primary prevention trial of rosuvastatin 20 mg compared with placebo among men and women free of cardiovascular disease who had low-density lipoprotein cholesterol ( LDL-C ) < 130 mg/dl and high-sensitivity C-reactive protein ( hsCRP ) > or=2 mg/l , we performed a secondary analysis comparing cardiovascular and mortality outcomes among those with moderate CKD at study entry ( n = 3,267 ) with those with baseline eGFR > or=60 ml/min/1.73 m(2 ) ( n = 14,528 ) . Median follow-up was 1.9 years ( maximum 5 years ) . RESULTS Compared with those with eGFR > or=60 ml/min/1.73 m(2 ) , JUPITER participants with moderate CKD had higher vascular event rates ( hazard ratio [ HR ] : 1.54 , 95 % confidence interval [ CI ] : 1.23 to 1.92 , p = 0.0002 ) . Among those with moderate CKD , rosuvastatin was associated with a 45 % reduction in risk of myocardial infa rct ion , stroke , hospital stay for unstable angina , arterial revascularization , or confirmed cardiovascular death ( HR : 0.55 , 95 % CI : 0.38 to 0.82 , p = 0.002 ) and a 44 % reduction in all-cause mortality ( HR : 0.56 , 95 % CI : 0.37 to 0.85 , p = 0.005 ) . Median LDL-C and hsCRP reductions as well as side effect profiles associated with rosuvastatin were similar among those with and without CKD . Median eGFR at 12 months was marginally improved among those allocated to rosuvastatin as compared with placebo . CONCLUSIONS Rosuvastatin reduces first cardiovascular events and all-cause mortality among men and women with LDL-C < 130 mg/dl , elevated hsCRP , and concomitant evidence of moderate CKD . ( JUPITER-Crestor 20 mg Versus Placebo in Prevention of Cardiovascular [ CV ] Events ; NCT00239681 ) Cardiovascular ( CVS ) death accounts for almost a quarter of paediatric and young adult end stage kidney disease deaths ( 1 ) and traditional CVS risk factors are often evident at an early age in children with chronic kidney disease ( CKD ) . Endothelial dysfunction is a precursor of atherosclerosis ( 2 ) and it has been documented to be present by the first decade of life in children with CKD . ( 3 ) . Given that endothelial dysfunction occurs very early in the timeline of atherosclerosis , it would seem to be an attractive target for therapeutic intervention ( 4 ) . There is some evidence that statins may improve endothelial dysfunction in nephrotic syndrome ( 5 ) , and in adults with raised ( 6,7 ) and borderline raised ( 8) lipid levels . We therefore design ed an intervention trial in children with CKD to determine whether we could improve endothelial dysfunction by using an HMG CoA reductase inhibitor ( statin ) . Patients were included if lipid levels were ‡50th percentile ( rather than the more conventional 95th percentile ) because the risk of hyperlipidaemia seems to be continuous , evidence d by an almost linear correlation between increasing lipid levels and decreasing arterial distensibility in normal children ( 9 ) . The objective of this study was to assess the effect of statin-associated cholesterol lowering on endothelial function , lipoprotein levels , C reactive protein ( CRP ) , blood pressure ( BP ) and renal function in mildly hyperlipidaemic children with CKD stages 3–4 [ estimated glomerular filtration rate ( GFR ) ( 10 ) < 60 mL ⁄ min ⁄ 1.73 m ] . A prospect i ve , r and omized double-blinded placebo controlled , crossover trial of atorvastatin 10 mg daily for 8 weeks in children ( 5–17 years of age ; n = 8) with serum lipoprotein levels > 50th percentile was conducted ( i.e. each patient was studied before and after 8 weeks of placebo and atorvastatin with a 4-week washout period between treatment arms ) . Seven of eight children were taking Angiotensin Converting Enzyme Inhibitors ( ACE-inhibitors ) for renoprotection ( not hypertension ) . Endothelial function was measured non-invasively by study ing brachial artery reactivity by vascular ultrasound ( ATL HDI 5000 Phillips , Bothell , Washington , DC , USA ) ( 11 ) . Change in brachial artery endothelium-dependent flow-mediated dilatation ( FMD ) was the primary end-point . It was estimated that in a crossover design with scans before and after intervention , 10 patients would detect a significant change in FMD of 3.6 % ( 11 ) to provide 80 % power at the 5 % significance level . Unfortunately , placebo expiry and recruitment difficulty led to only eight patients participating in a pilot study . Patients were recruited from the renal clinic of Sydney Children ’s Hospital and South Eastern Area Health and Central Sydney Ethics Committees approved the study . Total cholesterol and LDL significantly decreased during treatment by a mean of 1.3 ± 0.3 mmol ⁄ L p < 0.0001 and 1.1 ± 0.3 mmol ⁄ L respectively p < 0.0001 ( paired student t test ) ( Table 1 ) . Baseline FMD was normal with a mean of 9.75 ± 0.39 % ( SEM ) and did not significantly alter after 8 weeks of atorvastatin ( 8.04 ± 1.02 % p = 0.18 ) ( Table 2 ) . No significant change was seen in creatinine , BP , CRP , liver function tests , or creatinine kinase levels with atorvastatin . There was no significant correlation ( Pearson ) between vascular reactivity studies and serum creatinine or estimated GFR . There was no correlation between lipid concentrations , BP , BMI and FMD or glyceryl trinitrate ( GTN ) studies . Atorvastatin therapy for 8 weeks did not alter endothelial function in children with CKD despite a dose which achieved a significant reduction in LDL cholesterol . We postulate this may be attributable to the FMD results that Acta Pædiatrica ISSN |
755 | 26,869,023 | There were higher risks of toxicity outcomes grade 3 or 4 diarrhoea and grade 1 or 2 alopecia , and a lower risk of grade 3 or 4 neutropenia in controls compared to the invervention group .
There was no overall survival benefit of the irinotecan and fluoropyrimidine treatment over irinotecan alone , thus both regimens remain reasonable options in treating patients with advanced or metastatic CRC . | BACKGROUND Chemotherapy is the treatment of choice in patients with advanced or metastatic colorectal cancer ( CRC ) where surgical resection of metastases is not an option .
Both irinotecan ( IRI ) and fluoropyrimidines are often included in first- or second- line chemotherapy treatment regimens in such patients .
However , it is not clear whether combining these agents is superior to irinotecan alone . | PURPOSE In metastatic colorectal cancer , phase III studies have demonstrated the superiority of fluorouracil ( FU ) with leucovorin ( LV ) in combination with irinotecan or oxaliplatin over FU + LV alone . This phase III study investigated two sequences : folinic acid , FU , and irinotecan ( FOLFIRI ) followed by folinic acid , FU , and oxaliplatin ( FOLFOX6 ; arm A ) , and FOLFOX6 followed by FOLFIRI ( arm B ) . PATIENTS AND METHODS Previously untreated patients with assessable disease were r and omly assigned to receive a 2-hour infusion of l-LV 200 mg/m(2 ) or dl-LV 400 mg/m(2 ) followed by a FU bolus 400 mg/m(2 ) and 46-hour infusion 2,400 to 3,000 mg/m(2 ) every 46 hours every 2 weeks , either with irinotecan 180 mg/m(2 ) or with oxaliplatin 100 mg/m(2 ) as a 2-hour infusion on day 1 . At progression , irinotecan was replaced by oxaliplatin ( arm A ) , or oxaliplatin by irinotecan ( arm B ) . RESULT Median survival was 21.5 months in 109 patients allocated to FOLFIRI then FOLFOX6 versus 20.6 months in 111 patients allocated to FOLFOX6 then FOLFIRI ( P = .99 ) . Median second progression-free survival ( PFS ) was 14.2 months in arm A versus 10.9 in arm B ( P = .64 ) . In first-line therapy , FOLFIRI achieved 56 % response rate ( RR ) and 8.5 months median PFS , versus FOLFOX6 which achieved 54 % RR and 8.0 months median PFS ( P = .26 ) . Second-line FOLFIRI achieved 4 % RR and 2.5 months median PFS , versus FOLFOX6 which achieved 15 % RR and 4.2 months PFS . In first-line therapy , National Cancer Institute Common Toxicity Criteria grade 3/4 mucositis , nausea/vomiting , and grade 2 alopecia were more frequent with FOLFIRI , and grade 3/4 neutropenia and neurosensory toxicity were more frequent with FOLFOX6 . CONCLUSION Both sequences achieved a prolonged survival and similar efficacy . The toxicity profiles were different BACKGROUND In the non-curative setting , the sequence in which anticancer agents are used , singly or in combination , may be important if patients are to receive the maximum period of disease control with the minimum of adverse effects . We compared sequential and combination chemotherapy strategies in patients with unpretreated advanced or metastatic colorectal cancer , who were regarded as not potentially curable irrespective of response . METHODS We studied patients with advanced colorectal cancer , starting treatment with non-curative intent . 2135 unpretreated patients were r and omly assigned to three treatment strategies in the ratio 1:1:1 . Strategy A ( control group ) was single-agent fluorouracil ( given with levofolinate over 48 h every 2 weeks ) until failure , then single-agent irinotecan . Strategy B was fluorouracil until failure , then combination chemotherapy . Strategy C was combination chemotherapy from the outset . Within strategies B and C , patients were r and omly assigned to receive , as the combination regimen , fluorouracil plus irinotecan ( groups B-ir and C-ir ) or fluorouracil plus oxaliplatin ( groups B-ox and C-ox ) . The primary endpoint was overall survival , analysed by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N 79877428 . RESULTS Median survival of patients allocated to control strategy A was 13.9 months . Median survival of each of the other groups was longer ( B-ir 15.0 , B-ox 15.2 , C-ir 16.7 , and C-ox 15.4 months ) . However , log-rank comparison of each group against control showed that only C-ir -- the first-line combination strategy including irinotecan -- satisfied the statistical test for superiority ( p=0.01 ) . Overall comparison of strategy B with strategy C was within the predetermined non-inferiority boundary of HR=1.18 or less ( HR=1.06 , 90 % CI 0.97 - 1.17 ) . INTERPRETATION Our data challenge the assumption that , in this non-curative setting , maximum tolerable treatment must necessarily be used first-line . The staged approach of initial single-agent treatment up grade d to combination when required is not worse than first-line combination , and is an alternative option for discussion with patients This study evaluates the efficacy of capecitabine using data from a large , well-characterised population of patients with metastatic colorectal cancer ( mCRC ) treated in two identically design ed phase III studies . A total of 1207 patients with previously untreated mCRC were r and omised to either oral capecitabine ( 1250 mg m−2 twice daily , days 1−14 every 21 days ; n=603 ) or intravenous ( i.v . ) bolus 5-fluorouracil/leucovorin ( 5-FU/LV ; Mayo Clinic regimen ; n=604 ) . Capecitabine demonstrated a statistically significant superior response rate compared with 5-FU/LV ( 26 vs 17 % ; P<0.0002 ) . Subgroup analysis demonstrated that capecitabine consistently result ed in superior response rates ( P<0.05 ) , even in patient subgroups with poor prognostic indicators . The median time to response and duration of response were similar and time to progression ( TTP ) was equivalent in the two arms ( hazard ratio ( HR ) 0.997 , 95 % confidence interval ( CI ) 0.885–1.123 , P=0.95 ; median 4.6 vs 4.7 months with capecitabine and 5-FU/LV , respectively ) . Multivariate Cox regression analysis identified younger age , liver metastases , multiple metastases and poor Karnofsky Performance Status as independent prognostic indicators for poor TTP . Overall survival was equivalent in the two arms ( HR 0.95 , 95 % CI 0.84–1.06 , P=0.48 ; median 12.9 vs 12.8 months , respectively ) . Capecitabine results in superior response rate , equivalent TTP and overall survival , an improved safety profile and improved convenience compared with i.v . 5-FU/LV as first-line treatment for MCRC . For patients in whom fluoropyrimidine monotherapy is indicated , capecitabine should be strongly considered . Following encouraging results from phase I and II trials , r and omised trials are evaluating capecitabine in combination with irinotecan , oxaliplatin and radiotherapy . Capecitabine is a suitable replacement for i.v . 5-FU as the backbone of colorectal cancer therapy Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more PURPOSE To verify the experience of the GOIM in the treatment of advanced colorectal cancer patients with the FOLFIRI combination therapy . PATIENTS AND METHODS Patients entered in three consecutive trials of the GOIM ( protocol s no. 9706 , 9901 , and 2301 ) were reported in this analysis . A total of 287 chemotherapy-naive patients were treated with FOLFIRI regimen : Irinotecan 180 mg/m(2 ) on day 1 with LV5FU2 regimen ( LV at 100 mg/m(2 ) administered as a 2-hour infusion before FU at 400 mg/m(2 ) as an intravenous bolus injection , and FU at 600 mg/m(2 ) as a 22-hour infusion immediately after 5FU bolus injection on day 1 and 2 ) ; the treatment was repeated every 2 weeks . RESULTS 287 patients entered in these three trials , and 264 ( 92 % ) were evaluable for response . The overall response rate was 34.5 % ( 95 % confidence interval [ CI ] : 29 % to 40 % ) . When only assessable patients were analyzed , overall response rate was 37 % ( 95 % CI : 31 % to 43 % ) . Median time to progression , median duration of response and survival were 7 months , 10.5 months and 14 months , respectively . All but three patients were evaluable for toxicity which was globally mild ; grade 3 - 4 toxicity was uncommon , and gastrointestinal disturbances were the most common . CONCLUSIONS FOLFIRI regimen is effective and well-tolerated as first-line treatment in patients with advanced colorectal cancer . Further studies needed to evaluate the improvement in results with the addition of new drugs to this combination therapy One hundred and ninety-three patients were assigned to receive 5-FU/LV , irinotecan and oxaliplatin in five different sequential treatment groups : Mayo Clinic Regimen ( MCR ) + LV5FU2 ( group A ) ; MCR + irinotecan ( 350 mg/m2 ) ( group B ) ; MCR + FOLFIRI ( group C ) ; MCR + FOLFOX4 ( group D ) ; FOLFIRI + FOLFOX4 ( group E ) . The results were as follows : group A ( 32 patients ) , median overall survival ( OS ) 14 months , median time to progression ( TTP1 ) 6 months , median TTP2 5 months , response rate ( RR1 ) 22 % , RR2 25 % ; group B ( 27 patients ) , OS 11 months , TTP1 6 months , TTP2 3 months , RR1 22 % , RR2 19 % ; group C ( 43 patients ) , OS 14 months , TTP1 5 months , TTP2 5 months , RR1 12 % , RR2 19 % ; group D ( 45 patients ) , OS 15 months , TTP1 5 months , TTP2 4 months , RR1 18 % , RR2 20 % ; group E ( 46 patients ) , OS 19 months , TTP1 9 months , TTP2 5 months , RR1 39 % , RR2 25 % . There was a significant difference in OS ( p < 0.005 ) between groups E vs. B and A , D vs. B. Sequential therapy with 3 active drugs ( FOLFIRI + FOLFOX4 ) was the most efficacious combination in comparison with any other two drug combinations applied in our study This multicenter , Phase II trial was performed to evaluate the antitumor activity and toxicity of irinotecan ( CPT‐11 ) in patients with metastatic colorectal carcinoma that had recurred or progressed after 5‐fluorouracil (5‐FU)‐based chemotherapy BACKGROUND Three different therapeutic regimens of irinotecan ( CPT-11 ) in combination with 5-fluorouracil ( 5-FU ) and folinic acid ( FA ) were evaluated for efficacy and safety in the first-line therapy of advanced colorectal cancer . PATIENTS AND METHODS Patients were r and omly assigned to receive intravenously either : CPT-11 125 mg/m(2 ) , FA 20 mg/m(2 ) followed by 5-FU 500 mg/m(2 ) bolus , weekly for 4 weeks ( arm A , Saltz regimen ) ; or CPT-11 180 mg/m(2 ) day 1 then FA 200 mg/m(2 ) over 2 h and 5-FU 400 mg/m(2 ) bolus and 5-FU 600 mg/m(2 ) 22-h infusion on days 1 and 2 , every 2 weeks ( arm B , Douillard regimen ) ; or CPT-11 350 mg/m(2 ) ( days 1 and 43 ) alternating with FA 20 mg/m(2)/day followed by 5-FU bolus 425 mg/m(2)/day during 5 days ( days 22 - 26 ) ( arm C , Mayo Clinic regimen ) . RESULTS A total of 154 patients were included in the study ( arm A , 51 patients ; arm B , 53 ; arm C , 50 ) . Overall response rates for the intention-to-treat population s were 33 % [ 95 % confidence interval ( CI ) 21 % to 48 % ] , 42 % ( 95 % CI 28 % to 56 % ) and 30 % ( 95 % CI 18 % to 45 % ) for arms A , B and C , respectively . Median times to progression were 6 , 8 and 7 months for arms A , B and C , respectively . Median survival times were 15 , 12 and 17 months for arms A , B and C , respectively . Overall response rates for the evaluable patient population s were 40 % ( 95 % CI 24 % to 58 % ) in arm A , 44 % ( 95 % CI 29 % to 60 % ) in arm B and 31 % ( 95 % CI 17 % to 47 % ) in arm C. Neutropenia was the main serious adverse event in arms A ( 30 % of patients ) and C ( 22 % of patients ) but occurred in only 8 % of patients in arm B. Delayed diarrhea was the main severe adverse event for the three regimens , from 15 % to 22 % . CONCLUSION All three regimens were highly active . The biweekly combination of CPT-11 and 5-FU/FA ( arm B ) was notable for its low incidence of grade 3/4 neutropenia . The incidence of grade 3/4 delayed diarrhea was equivalent for the three treatment arms PURPOSE The combination regimen CPT-11 plus bolus and infusion 5-fluorouracil ( 5-FU ) with high-dose leucovorin ( hybrid regimen LV5FU2 ) has been tested for activity and toxicity against advanced colorectal carcinoma in a r and omised , multicenter phase II trial . PATIENTS AND METHODS A total of 102 chemotherapy-naïve patients were r and omised in a 1:2 fashion to receive : leucovorin 100 mg/m2 administered as a two-hour infusion before 5-FU 400 mg/m2 as an intravenous bolus , and FU 600 mg/m2 as a 22-hour infusion immediately after 5-FU bolus injection repeated on days 1 and 2 ( LV5FU2 regimen , arm A , 34 patients ) or CPT-11 at 180 mg/m2 ( 150 mg/m2 for patients of age > or = 70 and < 75 years ) only on day 1 immediately before LV5FU2 therapy ( LV5FU2 + CPT-11 regimen , arm B 68 patients ) . Both treatments were repeated every two weeks . The presence of a calibration arm assured consistency and more realistic evaluation of results achieved with the LV5FU2 + CTP-II regimen . RESULTS Thirty-three and sixty-four patients were evaluable in arm A and B , respectively . The overall response rate was 18 % in arm A ( 95 % CI : 7%-34 % ) and 40 % in arm B ( 95 % CI : 28%-52 % ) . Median time to progression , median duration of response and survival were similar in both groups . Responders ( CR + PR ) survived statistically longer than non-responders only in arm B ( 20 vs. 10 months , P = 0.0016 ) . All patients were evaluable for toxicity which was mild in both groups ; gastrointestinal disturbances were the most common . There were no treatment-related deaths . Grade 3 - 4 toxicity was uncommon in both arms . CONCLUSIONS The addition of CPT-11 to the hybrid LV5FU2 regimen provided a significant overall response rate ( 40 % ) with relatively mild toxicity . The overall response rate was 18 % in patients treated with LV5FU2 alone in the calibration arm . Thus , considering other encouraging data from the literature , the CPT-11 + FU-LV combination therapy can be regarded as a new , very effective treatment option for first-line treatment of advanced colorectal cancer patients PURPOSE We performed this phase III study to compare the irinotecan , leucovorin ( LV ) , and fluorouracil ( FU ) regimen ( FOLFIRI ) versus the oxaliplatin , LV , and FU regimen ( FOLFOX4 ) in previously untreated patients with advanced colorectal cancer . PATIENTS AND METHODS A total of 360 chemotherapy-naive patients were r and omly assigned to receive , every 2 weeks , either arm A ( FOLFIRI : irinotecan 180 mg/m(2 ) on day 1 with LV 100 mg/m(2 ) administered as a 2-hour infusion before FU 400 mg/m(2 ) administered as an intravenous bolus injection , and FU 600 mg/m(2 ) as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [ LV5FU2 ] ) or arm B ( FOLFOX4 : oxaliplatin 85 mg/m(2 ) on day 1 with LV5FU2 regimen ) . RESULTS One hundred sixty-four and 172 patients were assessable in arm A and B , respectively . Overall response rates ( ORR ) were 31 % in arm A ( 95 % CI , 24.6 % to 38.3 % ) and 34 % in arm B ( 95 % CI , 27.2 % to 41.5 % ; P = .60 ) . In both arms A and B , median time to progression ( TTP ; 7 v 7 months , respectively ) , duration of response ( 9 v 10 months , respectively ) , and overall survival ( OS ; 14 v 15 months , respectively ) were similar , without any statistically significant difference . Toxicity was mild in both groups : alopecia and gastrointestinal disturbances were the most common toxicities in arm A ; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms , and no statistical significant difference was observed . CONCLUSION There is no difference in ORR , TTP , and OS for patients treated with the FOLFIRI or FOLFOX4 regimen . Both therapies seemed effective as first-line treatment in these patients . The difference between these two combination therapies is mainly in the toxicity profile PURPOSE To assess the efficacy of irinotecan ( CPT-11 ) in the treatment of advanced colorectal cancer in both chemotherapy-naive and pretreated patients . PATIENTS AND METHODS Two hundred thirteen patients ( aged 18 to 75 years ) with metastatic colorectal cancer , World Health Organization ( WHO ) performance status < or = 2 , and life expectancy > or = 3 months were treated with CPT-11 350 mg/m2 every 3 weeks . All 178 patients eligible for efficacy analysis had not received more than one prior fluorouracil (5-FU)-based chemotherapy regimen ( adjuvant or palliative ) and had adequate hematologic , renal , and hepatic function . RESULTS Primary tumor sites were the colon ( 71 % ) and rectum ( 28 % ) . Sixty-six percent of the patients had > or = two metastatic sites . Ninety-eight percent of the patients had undergone previous surgery , and 77.5 % had received prior chemotherapy . Thirty-two of 178 eligible patients achieved on objective response ( four complete responses [ CRs ] and 28 partial responses [ PRs ] ; response rate , 18 % ; 95 % confidence interval , 12.6 % to 24.4 % ) , 65 were stable , and 59 progressed . The response rate was 17.7 % in the pretreated group and 18.8 % in the chemotherapy-naive group . Within the former subgroup , response rates of 16.1 % were reported in patients who were progressive on prior 5-FU chemotherapy and 19.1 % in patients who were progressive off such treatment . The median duration of objective response ( 9.1 months ) and median time to achievement of a response ( 9.3 weeks ) did not differ between chemotherapy-naive and pretreated patients . The most frequent adverse events were neutropenia , which developed in 80 % of the patients , delayed diarrhea ( 87 % ) , alopecia ( 88 % ) , fatigue ( 81 % ) , and nausea/vomiting ( 77 % ) . All these adverse events were manageable . Severe ( WHO grade 3 or 4 ) neutropenia was only observed in 18 % of the cycles , leukopenia in 11 % , delayed diarrhea in 11 % , and nausea and vomiting in 3 % . Development of simultaneous grade 3 or 4 neutropenia and delayed diarrhea during 4 % of the cycles was the safety issue of greatest concern . CONCLUSION CPT-11 has definite activity in the treatment of advanced metastatic colorectal cancer both in chemotherapy-naive and in pretreated patients who experienced disease progression on 5-FU , which suggests a lack of cross-resistance between CPT-11 and 5-FU . Diarrhea and neutropenia , the major toxicities of CPT-11 , contribute to the risk to develop febrile neutropenic sepsis Longitudinal quality of life ( QOL ) assessment is infrequently made in adjuvant therapy for colorectal cancer ( CRC ) . This analysis aims to assess QOL and quality adjusted survival ( QAS ) in patients receiving adjuvant 5-FU for stage II and III CRC . We performed a multicentre study in which 801 patients were r and omised to 6 months of bolus 5-FU/leucovorin ( LV n = 404 ) or 12 weeks of protracted venous infusion ( PVI ) 5-FU ( n = 397 ) . There were significant differences in the deterioration of QOL scores at week 2 with bolus 5-FU/LV compared to PVI 5-FU ( P < 0.001 ) , coinciding with toxicity peak during the first cycle . Following week 12 , global QOL recovered to baseline when PVI 5-FU was stopped but this was delayed with bolus 5-FU/LV until completion at week 24 . QOL scores significantly improved in both arms during follow-up ( P < 0.001 ) and reached a plateau by year 1 without incremental improvement between years 2 and 5 . There was a trend towards better QAS with PVI 5-FU . Twelve weeks of adjuvant PVI 5-FU was associated with significantly better QOL during treatment and faster time to recovery compared to 6 months of bolus 5-FU/LV |
756 | 28,865,809 | Three important mechanisms were present in all the most effective interventions but absent in all the least effective : 1/ showing families how to change : a ) providing child physical activity sessions , b ) delivering practical behaviour change strategy sessions , c ) providing calorie intake advice ; 2/ ensuring all the family are on board : a ) delivering discussion /education sessions for both children and parents , b ) delivering child-friendly sessions , c ) aim ing to change behaviours across the whole family ; 3/ enabling social support for both parents and children by delivering both child group sessions and parent group sessions .
To conclude , programmes should ensure the whole family is on board the programme , that parents and children can receive social support and are not just told what to change , but shown how | This study aim ed to identify critical features of successful lifestyle weight management interventions for overweight children ( 0 - 11years ) . | OBJECTIVE . The objective of this study was to determine whether a generalizable best- practice individualized behavioral intervention reduced BMI z score relative to st and ard dietetic care among overweight children . METHODS . The design consisted of an assessor-blinded , r and omized , controlled trial involving 134 overweight children ( 59 boys , 75 girls ; BMI ≥ 98th centile relative to United Kingdom 1990 reference data for children aged 5–11 years ) who were r and omly assigned to a best- practice behavioral program ( intervention ) or st and ard care ( control ) . The intervention used family-centered counseling and behavioral strategies to modify diet , physical activity , and sedentary behavior . BMI z score , weight , objective ly measured physical activity and sedentary behavior , fat distribution , quality of life , and height z score were recorded at baseline and at 6 and 12 months . RESULTS . The intervention had no significant effect relative to st and ard care on BMI z score from baseline to 6 months and 12 months . BMI z score decreased significantly in both groups from baseline to 6 and 12 months . For those who complied with treatment , there was a significantly smaller weight increase in those in the intervention group compared with control subjects from baseline to 6 months . There were significant between-group differences in favor of the intervention for changes in total physical activity , percentage of time spent in sedentary behavior , and light-intensity physical activity . CONCLUSIONS . A generalizable , best- practice individualized behavioral intervention had modest benefits on objective ly measured physical activity and sedentary behavior but no significant effect on BMI z score compared with st and ard care among overweight children . The modest magnitude of the benefits observed perhaps argues for a longer-term and more intense intervention , although such treatments may not be realistic for many health care systems OBJECTIVE : To determine whether a 2-year family-based intervention using frequent contact and limited expert involvement was effective in reducing excessive weight compared with usual care . METHODS : Two hundred and six overweight and obese ( BMI ≥85th percentile ) children aged 4 to 8 years were r and omized to usual care ( UC ) or tailored package ( TP ) sessions at university research rooms . UC families received personalized feedback and generalized advice regarding healthy lifestyles at baseline and 6 months . TP families attended a single multidisciplinary session to develop specific goals suitable for each family , then met with a mentor each month for 12 months , and every third month for another 12 months to discuss progress and provide support . Outcome measurements ( anthropometry , question naires , dietary intake , accelerometry ) were obtained at 0 , 12 , and 24 months . RESULTS : BMI at 24 months was significantly lower in TP compared with UC children ( difference , 95 % confidence interval : –0.34 , –0.65 to –0.02 ) , as was BMI z score ( –0.12 , –0.20 to –0.04 ) and waist circumference ( –1.5 , –2.5 to –0.5 cm ) . TP children consumed more fruit and vegetables ( P = .038 ) and fewer noncore foods ( P = .020 ) than UC children , and fewer noncore foods were available in the home ( P = .002 ) . TP children were also more physically active ( P = .035 ) . No differences in parental feeding practice s , parenting , quality of life , child sleep , or behavior were observed . CONCLUSIONS : Frequent , low-dose support was effective for reducing excessive weight in predominantly mild to moderately overweight children over a 2-year period . Such initiatives could feasibly be incorporated into primary care Background : The WATCH IT programme was developed to address the needs of obese children from disadvantaged communities in Leeds and has been running since January 2004 . Results of the pilot phase , prior to a r and omised controlled trial , are presented . Methods : A process evaluation to assess success of implementation was conducted in December 2004 . User views ( parent and child ) were obtained by semi-structured interviews and focus groups . Change in BMI SD score was calculated for children attending between January 2004 and November 2005 . Results : A total of 94 children ( 49 girls , 45 boys ) , mean age ( SD ) 12.2 ( 2.0 ) years attended . They were moderately to severely obese ( mean BMI SDS 3.09 ( 0.45 ) , with low quality of life and self-image scores . There was a significant reduction in overweight at 6 months ( Δ BMI SD −0.07 ) , especially for teenagers ( Δ BMI SD −0.13 ) and girls ( Δ BMI SD −0.07 ) . The programme was successfully implemented . By December 2004 mean attendance was 2.1 ( 0.7 ) clinics per month , and sports sessions 3.3 ( 1.7 ) sessions per month . Fourteen children dropped out and non-attendance was low ( only 7.5 % sessions missed in 12 months ) . Qualitative research indicated significant appreciation of the service , with reported increase in self-confidence and friendships , and reduction in self-harm . Conclusion : WATCH IT offers a model for a community based service for obese children . The programme suggests that effective care can be delivered by health trainers supervised by health professionals , and so potentially provides a cost effective programme within children ’s communities . These findings are encouraging , and need to be substantiated by extension to other locations and evaluation by r and omised controlled trial OBJECTIVE There is a great need for solution-oriented studies and descriptions of interventions for pediatric obesity in real-world setting s. This report describes a group-based behavioral parent-only intervention to promote healthier lifestyle habits and reduce weight status in an obese 12-year-old female participant . METHOD The behavioral parent-only intervention program described was part of a r and omized controlled trial that evaluated the impact of 2 behavioral interventions that addressed dietary intake , physical activity , and weight status in overweight and obese youth living in rural setting s. Both the child and parent were targeted for behavior change . The intervention included 12 group sessions over 4 months . Behavioral strategies , including self-monitoring , goal setting , performance feedback , reinforcement , stimulus control , and instruction in behavioral parenting strategies were flexibly applied to meet the needs of the family . Assessment s were completed at baseline , month-4 posttreatment , and month-10 follow-up . RESULTS The parent attended 10 of 12 treatment sessions . At follow-up the child had lost 17 pounds and grew 1.7 in . in height . The child also experienced improved quality of dietary intake and a drop in the number of self-reported unhealthy weight control behaviors . The parent experienced no notable decrease or increase in BMI . CONCLUSIONS The report describes the successful application of a behavioral intervention to address pediatric obesity that uses a parent-only approach . It is hoped that this presentation will facilitate discussion and help encourage further presentations of how the flexible application of evidence d-based interventions can be applied in real-world setting To decrease BMI in overweight and obese children , improved dietary intake and increased physical activity are key elements . Our objective was to evaluate the impact of a 1-y food and physical activity intervention on energy and macronutrient intake in overweight and obese children . A r and omized open trial was conducted with 92 overweight or obese 10.4 ± 1.08-y-old children . The intervention included 14 group sessions with different themes regarding food and physical activity . Dietary intake was assessed with diet history interviews covering 14 d at baseline and 4-d food records after 1 y and was evaluated according to national dietary recommendations . The control group participated in the same measurements as the intervention group but did not take part in group sessions . After 1 y , both groups had decreased their energy intake ( EI ) relative to total energy expenditure , but the effect was more pronounced for the intervention group than for the control group . At 1 y follow-up , a larger proportion of children in the intervention group compared with the control group met the recommended intake of refined sugar ( P = 0.019 ) . However , the groups did not differ in the proportion children who met the recommended intake of dietary fiber . Further , SFA intake relative to total EI did not differ between the groups at 1 y follow-up . In conclusion , despite a rather comprehensive intervention , only modest effects were achieved with respect to reduced EI and improved macronutrient intake Background / Objectives : To determine if a multi-component family focused education package is more effective than a waiting list control group in treating overweight and obese children . Subjects/ Methods : A 2-year r and omised controlled trial ; 65 overweight and obese children aged 6–14 years were allocated to active intervention in either the first or second year , with body composition monitoring alone in the control period . Anthropometric measurements were undertaken at six monthly intervals and a 7-day food and activity diary were issued . Results : Over the 2 years of the study body mass index ( BMI ) SDS ( z score ) fell significantly in the intervention/control ( I/C ) group , but not in the control/intervention ( C/I ) group . The difference between groups was 0.3 , which was borderline significant ( 95 % confidence interval ( 95 % CI ) −0.62 to 0.02 , P=0.06 ) before adjusting for potential confounding factors . Thirty-three percent of the I/C group and 12 % of the C/I group achieved the target reduction of 0.5 BMI SDS . The I/C group had a significantly greater reduction in the percentage with a BMI above the 99.6th centile at 24 months ( P=0.04 ) and gained 5.7 kg less over the time of the study . There were no significant differences between groups for mean percentage attendance at physical activity sessions ( I/C group=24.1 % , 95 % CI , 15.4–32.9 ; C/I group=31.7 % , 95 % CI , 22.4–41.1 , P=0.229 ) . Conclusions : Children given active intervention followed by body composition monitoring alone reduced their BMI SDS , and fewer children were classified as grossly overweight by the end of the study . If these findings are true , there are important implication s for the provision of services managing overweight in the community Background This study evaluates the effects of an intervention performed by youth health care professionals on child health behaviors . The intervention consisted of offering healthy lifestyle counseling to parents of overweight ( not obese ) 5-year-old children . Effects of the intervention on the child having breakfast , drinking sweet beverages , watching television and playing outside were evaluated . Methods Data were collected with the ' Be active , eat right ’ study , a cluster r and omized controlled trial among nine youth health care centers in the Netherl and s. Parents of overweight children received lifestyle counseling according to the intervention protocol in the intervention condition ( n = 349 ) and usual care in the control condition ( n = 288 ) . Parents completed question naires regarding demographic characteristics , health behaviors and the home environment at baseline and at 2-year follow-up . Cluster adjusted regression models were applied ; interaction terms were explored . Results The population for analysis consisted of 38.1 % boys ; mean age 5.8 [ sd 0.4 ] years ; mean BMI SDS 1.9 [ sd 0.4 ] . There were no significant differences in the number of minutes of outside play or television viewing a day between children in the intervention and the control condition . Also , the odds ratio for having breakfast daily or drinking two or less glasses of sweet beverages a day showed no significant differences between the two conditions . Additional analyses showed that the odds ratio for drinking less than two glasses of sweet beverages at follow-up compared with baseline was significantly higher for children in both the intervention ( p < 0.001 ) and the control condition ( p = 0.029 ) . Conclusions Comparison of the children in the two conditions showed that the intervention does not contribute to a change in health behaviors . Further studies are needed to investigate opportunities to adjust the intervention protocol , such as integration of elements in the regular well-child visit . The intervention protocol for youth health care may become part of a broader approach to tackle childhood overweight and obesity . Trial registration Current Controlled Trials IS RCT BACKGROUND Comparative effectiveness research ( CER ) evidence on childhood obesity provides the basis for effective screening and management strategies in pediatric primary care . The uses of health information technology including decision support tools in the electronic health records ( EHRs ) , as well as remote and mobile support to families , offer the potential to accelerate the adoption of childhood obesity CER evidence . METHODS / DESIGN The Study of Technology to Accelerate Research ( STAR ) is a three-arm , cluster-r and omized controlled trial being conducted in 14 pediatric offices in Massachusetts design ed to enroll 800 , 6 to 12 year old children with a body mass index ( BMI ) ≥ 95th percentile seen in primary care at those practice s. We will examine the extent to which computerized decision support tools in the EHR delivered to primary care providers at the point of care , with or without direct-to-parent support and coaching , will increase adoption of CER evidence for management of obese children . Direct-to-parent intervention components include telephone coaching and twice-weekly text messages . Point-of-care outcomes include obesity diagnosis , nutrition and physical activity counseling , and referral to weight management . One-year child-level outcomes include changes in BMI and improvements in diet , physical activity , screen time , and sleep behaviors , as well as cost and cost-effectiveness . CONCLUSIONS STAR will determine the extent to which decision support tools in EHRs with or without direct-to-parent support will increase adoption of evidence -based obesity management strategies in pediatric practice and improve childhood obesity-related outcomes Objective : The aim of the study was to compare the efficacy of group treatment stressing a health-promoting lifestyle with routine counseling in the treatment of childhood obesity . Design and subjects : Seventy obese children ( weight for height 115–182 % ) aged 7–9 years were r and omized either to routine counseling ( two appointments for children ) or to family-based group treatment ( 15 separate sessions for parents and children ) . These sessions included nutrition education , physical activity education and behavioral therapy . Outcome measures : Children 's weights and heights were measured at baseline , after the 6-month intervention and after the 6-month follow-up . The change of weight for height based on Finnish growth charts was used as the primary , and changes in body mass index ( BMI ) and BMI st and ard deviation scores ( BMI -SDS ) as secondary outcome measures . Results : Children attending the group treatment lost more weight for height ( 6.8 % ) than children receiving routine counseling ( 1.8 % ) ( P=0.001 ) . The difference was significant when the data were analyzed in four groups by the cut-off limits of 0 , −5 and −10 % for the change in weight for height . The respective decreases in BMI were 0.8 vs 0.0 ( P=0.003 ) and in BMI -SDS 0.3 vs 0.2 ( P=0.022 ) . The results remained similar in adjusted analyses . Both group and routine programs were feasible with a high , 87–99 % , participation rate in sessions and appointments and very low , 3 % or less , attrition rate from the programs . Six months after the intervention , beneficial effects were partly lost , but for changes in weight for height and BMI , the differences between the two treatment programs still were significant , and for BMI -SDS , there was a trend . Conclusions : Family-based group treatment that stresses a health-promoting lifestyle and is given separately for parents and children , offers an effective mode of therapy to treat obese school-aged children BACKGROUND & AIMS Little is known on the long-term effects of obesity intervention programs in preschool-aged children . We compared the long-term effects of a multidisciplinary treatment program with a usual-care program in seventy-five 3- to 5-year-old overweight or obese children who had participated in a r and omized controlled clinical trial . METHODS A follow-up study collecting data at 18 and 36 months after starting both programs . The multidisciplinary program consisted of diet counseling , exercise sessions teaching motor skills and focusing on an active lifestyle , and psychoeducation for parents . Outcome measures were changes in anthropometry and body composition , determined by bioelectrical impedance analysis and ultrasound . RESULTS At the end of the 16-week treatment program , the multidisciplinary intervention showed a greater decrease in body mass index z score ( BMI -z ) ( mean ( SD ) 0.2 ( 0.1 ) ) and waist circumference z score ( WC-z ) ( mean ( SD ) 0.3 ( 0.1 ) ) , than usual-care . During the 36-month follow-up , a significant overall treatment effect of the multidisciplinary intervention program was demonstrated on BMI -z ( 0.28 , 95 % CI 0.03 - 0.54 ) and abdominal subcutaneous fat ( SCF ) ( 0.23 , 95 % CI 0.01 - 0.45 ) , compared with the usual-care program . CONCLUSIONS A multidisciplinary intervention program in 3- to 5-year-old overweight and obese children shows greater long-term effects on reductions in BMI -z and SCF , compared with a usual-care program Background Despite record rates of childhood obesity , effective evidence -based treatments remain elusive . While prolonged tertiary specialist clinical input has some individual impact , these services are only available to very few children . Effective treatments that are easily accessible for all overweight and obese children in the community are urgently required . General practitioners are logical care providers for obese children but high- quality trials indicate that , even with substantial training and support , general practitioner care alone will not suffice to improve body mass index ( BMI ) trajectories . HopSCOTCH ( the Shared Care Obesity Trial in Children ) will determine whether a shared-care model , in which paediatric obesity specialists co-manage obesity with general practitioners , can improve adiposity in obese children . Design R and omised controlled trial nested within a cross-sectional BMI survey conducted across 22 general practice s in Melbourne , Australia . Participants Children aged 3–10 years identified as obese by Centers for Disease Control criteria at their family practice , and r and omised to either a shared-care intervention or usual care . InterventionA single multidisciplinary obesity clinic appointment at Melbourne ’s Royal Children ’s Hospital , followed by regular appointments with the child ’s general practitioner over a 12 month period . To support both specialist and general practice consultations , web-based shared-care software was developed to record assessment , set goals and actions , provide information to caregivers , facilitate communication between the two professional groups , and jointly track progress . Outcomes Primary - change in BMI z-score . Secondary - change in percentage fat and waist circumference ; health status , body satisfaction and global self-worth . Discussion This will be the first efficacy trial of a general-practitioner based , shared-care model of childhood obesity management . If effective , it could greatly improve access to care for obese children . Trial Registration Australian New Zeal and Clinical Trials Registry Background In the evaluation of childhood obesity interventions , few research ers undertake a rigorous feasibility stage in which the design and procedures of the evaluation process are examined . Consequently , phase III studies often demonstrate method ological weaknesses . Purpose Our aim was to conduct a feasibility trial of the evaluation of WATCH IT , a community obesity intervention for children and adolescents . We sought to determine an achievable recruitment rate ; acceptability of r and omisation , assessment procedures , and dropout rate ; optimal outcome measures for the definitive trial ; and a robust sample size calculation . Method Our goal was to recruit 70 participants over 6 months , r and omise them to intervention or control group , and retain participation for 12 months . Assessment s were taken prior to r and omisation and after 6 and 12 months . Procedures mirrored those intended for a full-scale trial , but multiple measures of similar outcomes were included as a means to determine those most appropriate for future research . Acceptability of the research and impact of the research on the programme were ascertained through interviewing participants and staff . Results We recruited 70 participants and found that r and omisation and data collection procedures were acceptable . Self-referral ( via media promotion ) was more effective than professional referral . Blinding of assessors was sustained to a reasonable degree , and optimal outcome measures for a full-scale trial were identified . Estimated sample size was significantly greater than sample sized reported in published trials . There was some negative impact on the existing programme as a result of the research , a lesson for design ers of future trials . Limitations We successfully recruited socially disadvantaged families , but the majority of families were of White British nationality . The composition of the participants was an added valuable lesson , suggesting that recruitment strategies to obtain a more heterogeneous ethnic sample warrant consideration in future research . Conclusions This study provided us with confidence that we can run a phase III multi-centre trial to test the effectiveness of WATCH IT . Importantly , it was invaluable in informing the design not only of that trial but also of future evaluations of childhood obesity treatment interventions Background The prevalence of childhood obesity , which has seen a rapid increase over the last decade , is now considered a major public health problem . Current treatment options are based on the two important frameworks of school- and family-based interventions ; however , most research has yet to compare the two frameworks in the treatment of childhood obesity . The objective of this review is to compare the effectiveness of school-based intervention with family-based intervention in the treatment of childhood obesity . Methods Data bases such as Medline , Pub med , CINAHL , and Science Direct were used to execute the search for primary research papers according to inclusion criteria . The review included a r and omised controlled trial and quasi-r and omised controlled trials based on family- and school-based intervention frameworks on the treatment of childhood obesity . Results The review identified 1231 articles of which 13 met the criteria . Out of the thirteen studies , eight were family-based interventions ( n = 8) and five were school-based interventions ( n = 5 ) with total participants ( n = 2067 ) . The participants were aged between 6 and 17 with the study duration ranging between one month and three years . Family-based interventions demonstrated effectiveness for children under the age of twelve and school-based intervention was most effective for those aged between 12 and 17 with differences for both long-term and short-term results . Conclusions The evidence shows that family- and school-based interventions have a considerable effect on treating childhood obesity . However , the effectiveness of the interventional frameworks depends on factors such as age , short- or long-term outcome , and method ological quality of the trials . Further research studies are required to determine the effectiveness of family- and school-based interventions using primary outcomes such as weight , BMI , percentage overweight and waist circumference in addition to the aforementioned factors Background E-health initiatives hold promise to improve shared-care models of health care . In 2008–2011 we developed and trialled web-based software to facilitate a r and omised trial of a shared-care approach for childhood obesity involving General Practitioners ( GPs ) working with tertiary specialists . We describe the software ’s development , implementation and evaluation , and make recommendations for future e-health initiatives . The web-based software was design ed with the goals of allowing both GPs and specialists to communicate and review patient progress ; integrating with existing GP software ; and supporting GPs to deliver the structured intervention . Specifically , we aim ed to highlight the challenges inherent in this process , and report on the extent to which the software ultimately met its implementation and user aims . Methods The study was conducted at the Royal Children ’s Hospital and 22 general practice s across Melbourne , Australia . Participants comprised 30 GPs delivering the shared-care intervention . Outcomes included the following . ( 1 ) GPs ’ pre-specified software requirements : transcribed from two focus groups and analysed for themes using content analysis . ( 2 ) Software implementation and performance based on the experience of the research team and GPs . ( 3 ) GP users ’ evaluation collected via question naire . ( 4 ) Software usage collected via GP question naire and qualified through visual inspection of the software meta- data . Results Software implementation posed difficult and at times disabling technological barriers ( e.g. out- date d hardware , poor internet connections ) . The software ’s speed and inability to seamlessly link with day-to-day software was a source of considerable frustration . Overall , GPs rated software usability as poor , although most ( 68 % ) felt that the structure and functionality of the software was useful . Recommendations for future e-health initiatives include thorough scoping of IT systems and server speed , testing across diverse environments , automated pre-requisite checks and up grade s of processors/memory where necessary , and user-created usernames and passwords . Conclusions GPs are willing to embrace novel technologies to support their practice . However , implementation remains challenging mainly for technical reasons , and this precludes further evaluation of potential user-specific barriers . These findings could inform future e-health ventures into shared-care , and highlight the need for an appropriate infrastructure . Trial registration Australian New Zeal and Clinical Trials Registry : ACTRN126080000553 Introduction Lifestyle Triple P is a general parenting intervention which focuses on preventing further excessive weight gain in overweight and obese children . The objective of the current study was to assess the effectiveness of the Lifestyle Triple P intervention in the Netherl and s. Method We used a parallel r and omized controlled design to test the effectiveness of the intervention . In total , 86 child-parent triads ( children 4–8 years old , overweight or obese ) were recruited and r and omly assigned ( allocation ratio 1:1 ) to the Lifestyle Triple P intervention or the control condition . Parents in the intervention condition received a 14-week intervention consisting of ten 90-minute group sessions and four individual telephone sessions . Primary outcome measure was the children ’s body composition ( BMI z-scores , waist circumference and skinfolds ) . The research assistant who performed the measurements was blinded for group assignment . Secondary outcome measures were the children ’s dietary behavior and physical activity level , parenting practice s , parental feeding style , parenting style , and parental self-efficacy . Outcome measures were assessed at baseline and 4 months ( short-term ) and 12 months ( long-term ) after baseline . Multilevel multiple regression analyses were conducted to determine the effect of the intervention on primary and secondary outcome measures . Results No intervention effects were found on children ’s body composition . Analyses of secondary outcomes showed positive short-term intervention effects on children ’s soft-drink consumption and parental responsibility regarding physical activity , encouragement to eat , psychological control , and efficacy and satisfaction with parenting . Longer-term intervention effects were found on parent ’s report of children ’s time spent on sedentary behavior and playing outside , parental monitoring food intake , and responsibility regarding nutrition . Conclusion Although the Lifestyle Triple P intervention showed positive effects on some parent reported child behaviors and parenting measures , no effects were visible on children ’s body composition or objective ly measured physical activity . Several adjustments of the intervention content are recommended , for example including a booster session . Trial Registration Nederl and s Trial Register NTR BACKGROUND AND OBJECTIVE : Few studies have tested the impact of motivational interviewing ( MI ) delivered by primary care providers on pediatric obesity . This study tested the efficacy of MI delivered by providers and registered dietitians ( RDs ) to parents of overweight children aged 2 through 8 . METHODS : Forty-two practice s from the Pediatric Research in Office Setting s Network of the American Academy of Pediatrics were r and omly assigned to 1 of 3 groups . Group 1 ( usual care ) measured BMI percentile at baseline and 1- and 2-year follow-up . Group 2 ( provider only ) delivered 4 MI counseling sessions to parents of the index child over 2 years . Group 3 ( provider + RD ) delivered 4 provider MI sessions plus 6 MI sessions from a RD . The primary outcome was child BMI percentile at 2-year follow up . RESULTS : At 2-year follow-up , the adjusted BMI percentile was 90.3 , 88.1 , and 87.1 for groups 1 , 2 , and 3 , respectively . The group 3 mean was significantly ( P = .02 ) lower than group 1 . Mean changes from baseline in BMI percentile were 1.8 , 3.8 , and 4.9 across groups 1 , 2 , and 3 . CONCLUSIONS : MI delivered by providers and RDs ( group 3 ) result ed in statistically significant reductions in BMI percentile . Research is needed to determine the clinical significance and persistence of the BMI effects observed . How the intervention can be brought to scale ( in particular , how to train physicians to use MI effectively and how best to train RDs and integrate them into primary care setting s ) also merits future research OBJECTIVE : The aim of this study was to evaluate the effect of family pediatrician – led motivational interviews ( MIs ) on BMI of overweight ( 85th ≥ BMI percentile ≥95th ) children aged 4 to 7 years . METHODS : All the family pediatricians working in Reggio Emilia Province ( Italy ) were invited to participate in the study ; 95 % accepted . Specific training was provided . Parents were asked to participate in the trial if they recognized their child as overweight . Children were individually r and omly assigned to MIs or usual care . All children were invited for a baseline and a 12-month visit to assess BMI and lifestyle behaviors . The usual care group received an information leaflet , and the intervention group received 5 MI family meetings . The primary outcome was the individual variation of BMI , assessed by pediatricians unblinded to treatment groups . RESULTS : Of 419 eligible families , 372 ( 89 % ) participated ; 187 children were r and omized to MIs and 185 to the usual care group . Ninety-five percent of the children attended the 12-month visit . The average BMI increased by 0.49 and 0.79 during the intervention in the MI and control groups , respectively ( difference : –0.30 ; P = .007 ) . MI had no effect in boys or in children whose mothers had a low educational level . Positive changes in parent-reported lifestyle behaviors occurred more frequently in the MI group than in the control group . CONCLUSIONS : The pediatrician-led MI was overall effective in controlling BMI in these overweight children aged 4 to 7 years , even though no effect was observed in male children or when the mother ’s education level was low Objectives : To reduce gain in body mass index ( BMI ) in overweight/mildly obese children in the primary care setting . Design : R and omized controlled trial ( RCT ) nested within a baseline cross-sectional BMI survey . Setting : Twenty nine general practice s , Melbourne , Australia . Participants : ( 1 ) BMI survey : 2112 children visiting their general practitioner ( GP ) April – December 2002 ; ( 2 ) RCT : individually r and omized overweight/mildly obese ( BMI z-score < 3.0 ) children aged 5 years 0 months–9 years 11 months ( 82 intervention , 81 control).Intervention : Four st and ard GP consultations over 12 weeks , targeting change in nutrition , physical activity and sedentary behaviour , supported by purpose - design ed family material s . Main outcome measures : Primary : BMI at 9 and 15 months post-r and omization . Secondary : Parent-reported child nutrition , physical activity and health status ; child-reported health status , body satisfaction and appearance/self-worth . Results : Attrition was 10 % . The adjusted mean difference ( intervention – control ) in BMI was −0.2 kg/m2 ( 95 % CI : −0.6 to 0.1 ; P=0.25 ) at 9 months and −0.0 kg/m2 ( 95 % CI : −0.5 to 0.5 ; P=1.00 ) at 15 months . There was a relative improvement in nutrition scores in the intervention arm at both 9 and 15 months . There was weak evidence of an increase in daily physical activity in the intervention arm . Health status and body image were similar in the trial arms . Conclusions : This intervention did not result in a sustained BMI reduction , despite the improvement in parent-reported nutrition . Brief individualized solution-focused approaches may not be an effective approach to childhood overweight . Alternatively , this intervention may not have been intensive enough or the GP training may have been insufficient ; however , increasing either would have significant cost and re source implication s at a population level BACKGROUND The high prevalence of obesity in children in the UK warrants continuing public health attention . ' Families for Health ' is a family-based group programme for the treatment of childhood obesity . Significant improvements in body mass index ( BMI ) z-score ( -0.21 , 95 % CI : -0.35 to -0.07 , P = 0.007 ) and other health outcomes were seen in children at a 9-month follow-up . AIM To undertake a 2-year follow-up of families who attended ' Families for Health ' in Coventry , to assess long-term outcomes and costs . METHODS ' Families for Health ' is a 12-week programme with parallel groups for parents and children , addressing parenting skills , healthy lifestyles and emotional well-being . The intervention was delivered at a leisure centre in Coventry , Engl and , with 27 overweight or obese children aged 7 - 13 years ( 18 girls , 9 boys ) and their parents , from 21 families . A ' before- and -after ' evaluation was completed with 19 ( 70 % ) children followed up at 2 years . The primary outcome was change in BMI z-score from baseline ; secondary outcomes were children 's quality of life , parent-child relationships , eating/activity habits and parents ' mental health . Costs to deliver the intervention and to families were recorded . RESULTS Mean change in BMI z-score from baseline was -0.23 ( 95 % CI : -0.42 to -0.03 , P = 0.027 ) at the 2-year follow-up and eight ( 42 % ) children had a clinical ly significant reduction in BMI z-score . Significant improvements were seen in children 's quality of life and eating habits in the home , while there were sustained reductions in unhealthy foods and sedentary behaviour . Fruit and vegetable consumption and parent 's mental health were not significantly different at 2 years . Costs of the programme were £ 517 per family ( £ 402 per child ) , equivalent to £ 2543 per unit reduction in BMI z-score . CONCLUSIONS Improvements in BMI z-score and certain other outcomes associated with the ' Families for Health ' programme were sustained at the 2-year follow-up . ' Families for Health ' is a promising new childhood obesity intervention , and a r and omized controlled trial is now indicated BACKGROUND Interactive technologies have the potential to increase the reach and frequency of practical clinical interventions that assist the parents of overweight and at-risk children to promote healthy lifestyle behaviors for their families . DESIGN A practical RCT evaluated the relative effectiveness of three interventions to support parents of overweight or at-risk children to change the home environment to foster more healthful child eating and activity behaviors , thereby reducing child BMI and BMI z-scores . A secondary purpose was to determine the patterns of use and potential dose effect for the highest-intensity intervention . SETTING / PARTICIPANTS Parent- and -child ( aged 8 - 12 years ) dyads ( N=220 ) who received care from Kaiser Permanente Colorado were assigned r and omly to one of the three Family Connections ( FC ) interventions : FC-workbook , FC-group , or FC-interactive voice response ( IVR ) counseling . MAIN OUTCOME MEASURES Child BMI z-scores , as well as symptoms of eating disorders and body image , were assessed at baseline , 6 months , and 12 months . RESULTS The BMI z-scores of children assigned to the FC-IVR intervention were the only ones that decreased from baseline to 6 months ( 0.07 SD ) and from baseline to 12 months ( 0.08 SD , p<0.05 ) . Children whose parents completed at least six of the ten FC-IVR counseling calls had decreased BMI z-scores to a greater extent than children in the FC-workbook or FC-group interventions at both 6 months ( p<0.05 ) and 12 months ( p<0.01 ) . No intervention increased child symptoms of eating disorders or body dissatisfaction at any time point . CONCLUSIONS This trial demonstrated that automated telephone counseling can support the parents of overweight children to reduce the extent to which their children are overweight . TRIAL REGISTRATION NCT00433901 BACKGROUND : Pediatrician-led motivational interviewing can be an effective way of controlling BMI in overweight children in the short term . Its long-term efficacy is unknown . The primary aim was to determine whether the short-term ( 12-month ) impact of family pediatrician-led motivational interviews on the BMI of overweight children could be sustained in the long term ( 24 months ) , in the absence of any other intervention . METHODS : Children were recruited in 2011 by family pediatricians working in the province of Reggio Emilia , Italy , and r and omly allocated to receive either 5 interviews delivered over a 12-month period or usual care . Eligible participants were all 4- to 7-year-old overweight children resident in the province of Reggio Emilia who had been receiving care from the pediatrician for ≥12 months . The primary outcome of this study was individual variation in BMI between the baseline visit and the 24-month follow-up , assessed by pediatricians not blinded to treatment group allocation . RESULTS : Of 419 eligible families , 372 ( 89 % ) participated ; 187 children were r and omized to receive intervention and 185 to usual care . Ninety-five percent of the children attended the 12-month follow-up , and 91 % attended the 24-month follow-up . After the 12-month intervention period , BMI in the intervention group increased less than in the control group ( 0.46 and 0.78 , respectively ; difference −0.32 ; P = .005 ) . At the 24-month follow-up , the difference had disappeared ( 1.52 and 1.56 , respectively ; difference −0.04 ; P = .986 ) . CONCLUSIONS : The intervention lost its effectiveness within 1 year of cessation . Sustainable boosters are required for weight control and obesity prevention OBJECTIVE The objective of this study was to examine the efficacy of U.S. primary care paediatric obesity treatment recommendations , within two r and omized trials . METHODS Between November 2005 to September 2007 , 182 families ( children aged 4 - 9 years , body mass index [ BMI ] ≥85th percentile ) were recruited for two separate trials and r and omized within trial to a 6-month intervention . Each trial had one intervention that increased child growth-monitoring frequency and feedback to families ( GROWTH MONITORING ) . Each trial also had two interventions , combining GROWTH MONITORING with an eight-session , behavioural , parent-only intervention targeting two energy-balance behaviours ( Trial 1 : reducing snack foods and sugar-sweetened beverages [ DECREASE ] , and increasing fruits , vegetables and low-fat dairy [ INCREASE ] ; Trial 2 : decreasing sugar-sweetened beverages and increasing physical activity [ TRADITIONAL ] and increasing low-fat milk consumption and reducing television watching [ SUBSTITUTES ] ) . Child st and ardized BMI ( Z BMI ) and energy intake were assessed at 0 , 6 and 12 months . RESULTS In both trials , main effects of time were found for Z BMI , which decreased at 6 and 12 months ( P < 0.01 ) . In Trial 1 , Z BMI reduced from 0 to 6 months , which was maintained from 6 to 12 months ( ΔZ BMI 0 to 12 months = -0.12 ± 0.22 ) . In Trial 2 , Z BMI reduced from 0 to 6 and from 6 to 12 months ( ΔZ BMI 0 - 12 months = -0.16 ± 0.31 ) . For energy intake , main effects of time were found in both trials and intake reduced from 0 to 6 months ( P < 0.05 ) , with Trial 1 reducing intake from 0 to 12 months ( P < 0.05 ) . CONCLUSIONS All interventions improved weight status . Future research should examine effectiveness and translatability of these approaches into primary care setting OBJECTIVE The authors performed a group-based program for obese children and adolescents in Bavaria , Germany to enable them to establish a health-oriented lifestyle and to reduce overweight . The authors compared this program with a control approach based on the patients ' own initiative . DESIGN This is a controlled clinical trial . SETTING A nutrition program for out patients in a German university hospital . PARTICIPANTS Seventy-three obese patients aged 7 to 15 years ( mean 11.2 years ) were recruited by pediatricians and local newspaper reports and r and omized into intervention and control groups . Children and adolescents in each group were divided into 3 groups according to age--7 - 8 years , 9 - 10 years , and 11 - 13 years . Children were classified overweight ( defined as body mass index ( BMI ) > 90th percentile for age and gender ) , obese ( BMI > 97th percentile ) , and extremely obese ( BMI > 99.5th percentile ) , according to the European Childhood Obesity Group and the German Working Group on Pediatric Obesity , congruent with adult st and ards used to assess overweight and obesity . INTERVENTION Thirty-seven patients ( age 7 - 13 years , mean 10.9 years ) for the 1-year intervention . This intervention consisted of modules for physical activity , nutritional education , and coping strategies . The program was performed twice each week and incorporated parental participation and medical supervision , including laboratory tests . The obese controls ( n = 36 , age 8 - 15 years , mean 11.6 years ) received written therapeutic advice during a visit at 0 and 6 months in the outpatient clinic . MAIN OUTCOME MEASURE The primary outcome variable was the body mass index ( BMI ) z score . ANALYSIS Analysis of variance and t test were used , and a P value < .05 was considered significant . RESULTS There was a reduction of BMI z score in the active treatment group ( P < .05 ) , but not for controls . Moreover , the active group showed beneficial effects for body mass index ( BMI ) , fat mass , and systolic blood pressure 12 months after beginning the intervention . CONCLUSIONS AND IMPLICATION S Group-based programs for young , obese patients can be effective tools for establishing a health-oriented lifestyle and reducing the burden of obesity BACKGROUND . Parenting-skills training may be an effective age-appropriate child behavior-modification strategy to assist parents in addressing childhood overweight . OBJECTIVE . Our goal was to evaluate the relative effectiveness of parenting-skills training as a key strategy for the treatment of overweight children . DESIGN . The design consisted of an assessor-blinded , r and omized , controlled trial involving 111 ( 64 % female ) overweight , prepubertal children 6 to 9 years of age r and omly assigned to parenting-skills training plus intensive lifestyle education , parenting-skills training alone , or a 12-month wait-listed control . Height , BMI , and waist-circumference z score and metabolic profile were assessed at baseline , 6 months , and 12 months ( intention to treat ) . RESULTS . After 12 months , the BMI z score was reduced by ∼10 % with parenting-skills training plus intensive lifestyle education versus ∼5 % with parenting-skills training alone or wait-listing for intervention . Waist-circumference z score fell over 12 months in both intervention groups but not in the control group . There was a significant gender effect , with greater reduction in BMI and waist-circumference z scores in boys compared with girls . CONCLUSION . Parenting-skills training combined with promoting a healthy family lifestyle may be an effective approach to weight management in prepubertal children , particularly boys . Future studies should be powered to allow gender sub analysis OBJECTIVE To describe the impact of a parent-led , family-focused child weight management program on the food intake and activity patterns of pre-pubertal children . METHODS An assessor-blinded , r and omized controlled trial involving 111 ( 64 % female ) overweight , pre-pubertal children 6 - 9 years of age r and omly assigned to parenting-skills training plus intensive diet and activity education ( P + DA ) , parenting-skills training alone ( P ) , or a 12-month wait-listed control ( WLC ) . Study outcomes were assessed at baseline , 6 months , and 12 months . This paper presents data on food intake assessed via a vali date d 54-item parent-completed dietary question naire and activity behaviours assessed via a parent-report 20-item activity question naire . RESULTS Intake of energy-dense nutrient-poor foods was lower in both intervention groups at 6 months ( mean difference , P + DA - 1.5 serves [ CI - 2.0 ; -1.0 ] ; P - 1.0 serves [ -2.0 ; -0.5 ] ) and 12 months ( mean difference P + DA - 1.0 serves [ CI - 2.0 ; -0.5 ] ; P - 1.0 serves [ - 1.5 ; 0.0 ] ) compared to baseline . Intake of vegetables , fruit , breads and cereals , meat and alternatives and dairy foods remained unchanged . Regardless of study group there were significant reductions over time in the reported time spent engaged in small screen activities and an increase in the time reported spent in active play . CONCLUSION A child weight management intervention that promotes food intake in line with national dietary guidelines achieves a reduction in children 's intake of energy-dense , nutrient-poor foods . This was achieved without compromising intake of nutrient-rich food and changes were maintained even once the intervention ceased Objective To determine whether ascertainment of childhood obesity by surveillance followed by structured secondary prevention in primary care improved outcomes in overweight or mildly obese children . Design R and omised controlled trial nested within a baseline cross sectional survey of body mass index ( BMI ) . R and omisation and outcomes measurement , but not participants , were blinded to group assignment . Setting 45 family practice s ( 66 general practitioners ) in Melbourne , Australia . Participants 3958 children visiting their general practitioner in May 2005-July 2006 were surveyed for BMI . Of these , 258 children aged 5 years 0 months up to their 10th birthday who were overweight or obese by International Obesity Taskforce criteria were r and omised to intervention ( n=139 ) or control ( n=119 ) groups . Children who were very obese ( UK BMI z score ≥3.0 ) were excluded . Intervention Four st and ard consultations over 12 weeks targeting change in nutrition , physical activity , and sedentary behaviour , supported by purpose design ed family material s. Main outcomes measures Primary measure was BMI at 6 and 12 months after r and omisation . Secondary measures were mean activity count/min by 7-day accelerometry , nutrition score from 4-day abbreviated food frequency diary , and child health related quality of life . Differences were adjusted for socioeconomic status , age , sex , and baseline BMI . Results Of 781 eligible children , 258 ( 33 % ) entered the trial ; attrition was 3.1 % at 6 months and 6.2 % at 12 months . Adjusted mean differences ( intervention − control ) at 6 and 12 months were , for BMI , −0.12 ( 95 % CI −0.40 to 0.15 , P=0.4 ) and −0.11 ( −0.45 to 0.22 , P=0.5 ) ; for physical activity in counts/min , 24 ( −4 to 52 , P=0.09 ) and 11 ( −26 to 49 , P=0.6 ) ; and , for nutrition score , 0.2 ( −0.03 to 0.4 , P=0.1 ) and 0.1 ( −0.1 to 0.4 , P=0.2 ) . There was no evidence of harm to the child . Costs to the healthcare system were significantly higher in the intervention arm . Conclusions Primary care screening followed by brief counselling did not improve BMI , physical activity , or nutrition in overweight or mildly obese 5 - 10 year olds , and it would be very costly if universally implemented . These findings are at odds with national policies in countries including the US , UK , and Australia . Trial registration IS RCT N 52511065 ( www.is rct n.org IMPORTANCE Evidence of effective treatment of childhood obesity in primary care setting s is limited . OBJECTIVE To examine the extent to which computerized clinical decision support ( CDS ) delivered to pediatric clinicians at the point of care of obese children , with or without individualized family coaching , improved body mass index ( BMI ; calculated as weight in kilograms divided by height in meters squared ) and quality of care . DESIGN , SETTING , AND PARTICIPANTS We conducted a cluster-r and omized , 3-arm clinical trial . We enrolled 549 children aged 6 to 12 years with a BMI at the 95 % percentile or higher from 14 primary care practice s in Massachusetts from October 1 , 2011 , through June 30 , 2012 . Patients were followed up for 1 year ( last follow-up , August 30 , 2013 ) . In intent-to-treat analyses , we used linear mixed-effects models to account for clustering by practice and within each person . INTERVENTIONS In 5 practice s r and omized to CDS , pediatric clinicians received decision support on obesity management , and patients and their families received an intervention for self-guided behavior change . In 5 practice s r and omized to CDS + coaching , decision support was augmented by individualized family coaching . The remaining 4 practice s were r and omized to usual care . MAIN OUTCOMES AND MEASURES Smaller age-associated change in BMI and the Healthcare Effectiveness Data and Information Set ( HEDIS ) performance measures for obesity during the 1-year follow-up . RESULTS At baseline , mean ( SD ) patient age and BMI were 9.8 ( 1.9 ) years and 25.8 ( 4.3 ) , respectively . At 1 year , we obtained BMI from 518 children ( 94.4 % ) and HEDIS measures from 491 visits ( 89.4 % ) . The 3 r and omization arms had different effects on BMI over time ( P = .04 ) . Compared with the usual care arm , BMI increased less in children in the CDS arm during 1 year ( -0.51 [ 95 % CI , -0.91 to -0.11 ] ) . The CDS + coaching arm had a smaller magnitude of effect ( -0.34 [ 95 % CI , -0.75 to 0.07 ] ) . We found substantially greater achievement of childhood obesity HEDIS measures in the CDS arm ( adjusted odds ratio , 2.28 [ 95 % CI , 1.15 - 4.53 ] ) and CDS + coaching arm ( adjusted odds ratio , 2.60 [ 95 % CI , 1.25 - 5.41 ] ) and higher use of HEDIS codes for nutrition or physical activity counseling ( CDS arm , 45 % ; CDS + coaching arm , 25 % ; P < .001 compared with usual care arm ) . CONCLUSIONS AND RELEVANCE An intervention that included computerized CDS for pediatric clinicians and support for self-guided behavior change for families result ed in improved childhood BMI . Both interventions improved the quality of care for childhood obesity . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01537510 OBJECTIVE To examine the effectiveness of a primary care-based obesity intervention over the first year ( 6 intervention contacts ) of a planned 2-year study . DESIGN Cluster r and omized controlled trial . SETTING Ten pediatric practice s , 5 intervention and 5 usual care . PARTICIPANTS Four hundred seventy-five children aged 2 to 6 years with body mass index ( BMI ) in the 95th percentile or higher or 85th to less than 95th percentile if at least 1 parent was overweight ; 445 ( 93 % ) had 1-year outcomes . INTERVENTION Intervention practice s received primary care restructuring , and families received motivational interviewing by clinicians and educational modules targeting television viewing and fast food and sugar-sweetened beverage intake . OUTCOME MEASURES Change in BMI and obesity-related behaviors from baseline to 1 year . RESULTS Compared with usual care , intervention participants had a smaller , nonsignificant change in BMI ( -0.21 ; 95 % confidence interval [ CI ] , -0.50 to 0.07 ; P = .15 ) , greater decreases in television viewing ( -0.36 h/d ; 95 % CI , -0.64 to -0.09 ; P = .01 ) , and slightly greater decreases in fast food ( -0.16 serving/wk ; 95 % CI , -0.33 to 0.01 ; P = .07 ) and sugar-sweetened beverage ( -0.22 serving/d ; 95 % CI , -0.52 to 0.08 ; P = .15 ) intake . In post hoc analyses , we observed significant effects on BMI among girls ( -0.38 ; 95 % CI , -0.73 to -0.03 ; P = .03 ) but not boys ( 0.04 ; 95 % CI , -0.55 to 0.63 ; P = .89 ) and among participants in households with annual incomes of $ 50 000 or less ( -0.93 ; 95 % CI , -1.60 to -0.25 ; P = .01 ) but not in higher-income households ( 0.02 ; 95 % CI , -0.30 to 0.33 ; P = .92 ) . CONCLUSION After 1 year , the High Five for Kids intervention was effective in reducing television viewing but did not significantly reduce BMI We evaluated the efficacy of a 6-month clinic and home-based behavioral intervention ( Learning about Activity and Underst and ing Nutrition for Child Health ; LAUNCH ) to reduce obesity in preschool children ≥95th BMI percentile compared to enhanced st and ard of care ( Pediatrician Counseling ; PC ) . LAUNCH was a family-based behavioral intervention that taught parents to use child behavior management strategies to increase healthy eating and activity for their children and themselves . PC presented the same diet and activity recommendations , but was delivered in a one-time PC session . Eighteen children aged 2 - 5 years ( mean 4.71 ± 1.01 ) with an average BMI percentile of 98 ( ±1.60 ) and an overweight parent were r and omized to LAUNCH or PC . Assessment s were conducted at baseline , 6 months ( end of LAUNCH treatment ) and 12 months ( 6 months following LAUNCH treatment ) . LAUNCH showed a significantly greater decrease on the primary outcomes of child at month 6 ( post-treatment ) BMI z ( -0.59 ± 0.17 ) , BMI percentile ( -2.4 ± 1.0 ) , and weight gain ( -2.7 kg ± 1.2 ) than PC and this difference was maintained at follow-up ( month 12 ) . LAUNCH parents also had a significantly greater weight loss ( -5.5 kg ± 0.9 ) at month 6 and 12 ( -8.0 kg ± 3.5 ) than PC parents . Based on the data from this small sample , an intensive intervention that includes child behavior management strategies to improve healthy eating and activity appears more promising in reducing preschool obesity than a low intensity intervention that is typical of treatment that could be delivered in primary care Project STORY is a 3-arm , r and omized , planning and feasibility study assessing the effectiveness of two behavioral weight management interventions in an important and at-risk population , overweight children and their parents in medically underserved rural counties . Participants will include 90 parent-child dyads from rural counties in north central Florida . Families will be r and omized to one of three conditions : ( a ) a Family-Based Behavioral Group Intervention , ( b ) a Parent-Only Behavioral Group Intervention , and ( c ) a waitlist control condition . Child and parent participants will be assessed at baseline ( month 0 ) , post-treatment ( month 4 ) and follow-up ( month 10 ) . Assessment and intervention sessions will be held at Cooperative Extension offices within each local participating county . The primary outcome measure is change in child body mass index ( BMI ) z-score . Additional key outcome measures include child dietary intake , physical activity , self-esteem , body image , and parent BMI . The goals of the study are to ( a ) assess the feasibility of recruitment in rural setting s , ( b ) develop and evaluate training protocol for group leaders , ( c ) determine strategies to increase adherence to monitoring and goal setting protocol , ( d ) evaluate strategies for participant retention , ( e ) assess the relative cost-effectiveness of the interventions , ( f ) assess the acceptability of the intervention to families and Cooperative Extension administrators and personnel , and ( g ) if successful , estimate the sample size needed for a full-scale trial . This research has potential implication s for medically underserved rural communities with limited re sources and preventive health care services . If successful , a Parent-Only intervention program may provide a cost-effective and practical intervention for families in underserved rural communities Objective : We investigated the long-term efficacy of two childhood obesity treatment programs , routine counselling ( two appointments for children ) and group treatment ( 15 sessions separately for children and parents ) in a r and omised controlled trial . As published earlier , group treatment was more effective than routine counselling in the treatment of 7–9 year-old obese children in the short term . Design : The children 's heights and weights were measured 2 and 3 years after the beginning of the intervention and changes in weight for height , body mass index ( BMI ) and BMI st and ard deviation scores were used as outcome measures . Results : There were no significant differences between the treatment arms in the changes of outcome measures from baseline to 2- or 3-years follow-up visits . Conclusion : In conclusion , novel efforts are needed for the improvement of the long-term results of childhood obesity treatment programs OBJECTIVE To assess the effectiveness of parent-only vs family-based interventions for pediatric weight management in underserved rural setting s. DESIGN A 3-arm r and omized controlled clinical trial . SETTING All sessions were conducted at Cooperative Extension Service offices in underserved rural counties . PARTICIPANTS Ninety-three overweight or obese children ( 8 - 14 years old ) and their parent(s ) . INTERVENTION Families were r and omized to ( 1 ) a behavioral family-based intervention , ( 2 ) a behavioral parent-only intervention , or ( 3 ) a wait-list control group . OUTCOME MEASURE The primary outcome measure was change in children 's st and ardized body mass index ( BMI ) . RESULTS Seventy-one children completed posttreatment ( month 4 ) and follow-up ( month 10 ) assessment s. At the month 4 assessment , children in the parent-only intervention demonstrated a greater decrease in BMI z score ( mean difference [ MD ] , 0.127 ; 95 % confidence interval [ CI ] , 0.027 to 0.226 ) than children in the control condition . No significant difference was found between the family-based intervention and the control condition ( MD , 0.065 ; 95 % CI , -0.027 to 0.158 ) . At month 10 follow-up , children in the parent-only and family-based intervention groups demonstrated greater decreases in BMI z score from before treatment compared with those in the control group ( MD , 0.115 ; 95 % CI , 0.003 to 0.220 ; and MD , 0.136 ; 95 % CI , 0.018 to 0.254 , respectively ) . No difference was found in weight status change between the parent-only and family-based interventions at either assessment . CONCLUSIONS A parent-only intervention may be a viable and effective alternative to family-based treatment of childhood overweight . Cooperative Extension Service offices have the potential to serve as effective venues for the dissemination of obesity-related health promotion programs OBJECTIVE To assess the effects of a multidisciplinary intervention program for 3-year-old to 5-year-old overweight and obese children compared with a usual-care program . DESIGN R and omized controlled clinical trial conducted from October 2006 to March 2008 . SETTING Groningen Expert Center for Kids with Obesity at Beatrix Children 's Hospital , University Medical Center Groningen . PARTICIPANTS Seventy-five children ( 29 overweight , 46 obese ) aged 3 to 5 years . INTERVENTION A multidisciplinary intervention program vs a usual-care program . Anthropometry was performed and body composition was determined by bioelectrical impedance analysis and ultrasonography at the start and end of the 16-week program and 12 months after starting the intervention . MAIN OUTCOME MEASURES The actual weight reduction , change in body mass index ( BMI , calculated as weight in kilograms divided by height in meters squared ) , BMI z score , body fat percentage , and visceral fat in the multidisciplinary intervention group compared with a usual-care group . RESULTS At the end of the treatment program , children in the multidisciplinary intervention group showed a greater decrease in BMI , BMI z score , and waist circumference z score compared with children in the usual-care group . At 12 months , children in the intervention group showed greater decreases in BMI , BMI z score , waist circumference , and waist circumference z score compared with children in the usual-care group . Visceral fat showed a trend toward a higher decrease . CONCLUSIONS A multidisciplinary intervention program in 3-year-old to 5-year-old overweight and obese children had beneficial effects on anthropometry and body composition . The positive effects were still present 12 months after the start of the intervention . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N47185691 OBJECTIVE Tested two family-based behavioral treatments for obesity in preschool children , one meeting the Expert Committee guidelines for Stage 3 obesity intervention criteria ( LAUNCH-clinic ) and one exceeding Stage 3 ( LAUNCH with home visit [ LAUNCH-HV ] ) , compared with a Stage 1 intervention , pediatrician counseling ( PC ) . METHODS In all , 42 children aged 2 - 5 years with a body mass index ( BMI ) percentile of ≥95th were r and omized . A total of 33 met intent-to-treat criteria . Assessment s were conducted at baseline , Month 6 ( posttreatment ) , and Month 12 ( 6-month follow-up ) . RESULTS LAUNCH-HV demonstrated a significantly greater decrease on the primary outcome of change in BMI z-score ( BMI z ) pre- to posttreatment compared with PC ( p = .007 ) , whereas LAUNCH-clinic was not significantly different from PC ( p = .08 ) . Similar results were found for secondary outcomes . CONCLUSIONS LAUNCH-HV , but not LAUNCH-clinic , significantly reduced BMI z compared with PC by posttreatment , indicating the need for intensive behavioral intervention , including home visitation , to address weight management in obese preschool children Objective To determine whether general practice surveillance for childhood obesity , followed by obesity management across primary and tertiary care setting s using a shared care model , improves body mass index and related outcomes in obese children aged 3 - 10 years . Design R and omised controlled trial . Setting 22 family practice s ( 35 participating general practitioners ) and a tertiary weight management service ( three paediatricians , two dietitians ) in Melbourne , Australia . Participants Children aged 3 - 10 years with body mass index above the 95th centile recruited through their general practice between July 2009 and April 2010 . Intervention Children were r and omly allocated to one tertiary appointment followed by up to 11 general practice consultations over one year , supported by shared care , web based software ( intervention ) or “ usual care ” ( control ) . Research ers collecting outcome measurements , but not participants , were blinded to group assignment . Main outcome measures Children ’s body mass index z score ( primary outcome ) , body fat percentage , waist circumference , physical activity , quality of diet , health related quality of life , self esteem , and body dissatisfaction and parents ’ body mass index ( all 15 months post-enrolment ) . Results 118 ( 60 intervention , 56 control ) children were recruited and 107 ( 91 % ) were retained and analysed ( 56 intervention , 51 control ) . All retained intervention children attended the tertiary appointment and their general practitioner for at least one ( mean 3.5 ( SD 2.5 , range 1 - 11 ) ) weight management consultation . At outcome , children in the two trial arms had similar body mass index ( adjusted mean difference −0.1 ( 95 % confidence interval −0.7 to 0.5 ; P=0.7 ) ) and body mass index z score ( −0.05 ( −0.14 to 0.03 ) ; P=0.2 ) . Similarly , no evidence was found of benefit or harm on any secondary outcome . Outcomes varied widely in the combined cohort ( mean change in body mass index z score −0.20 ( SD 0.25 , range −0.97 - 0.47 ) ; 26 % of children resolved from obese to overweight and 2 % to normal weight . Conclusions Although feasible , not harmful , and highly rated by both families and general practitioners , the shared care model of primary and tertiary care management did not lead to better body mass index or other outcomes for the intervention group compared with the control group . Improvements in body mass index in both groups highlight the value of untreated controls when determining efficacy . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12608000055303 |
757 | 25,269,609 | Studies with older participants and predominantly male participants tended to report worse functional outcomes . | OBJECTIVES To quantify the prognosis of physical function following ankle fracture .
BACKGROUND Information about the course of recovery of physical function after ankle fracture is essential for patient care and health care policy .
The existing data have not previously been included in a meta- analysis . | Objective : Postoperative care for ankle fractures is generally 1 of 2 regimens : 1 ) functional treatment combined with early weightbearing ( EWB ) , or 2 ) immobilization in a cast/orthosis for 6 weeks without weightbearing ( 6WC ) . The objective of this study was 2-fold : 1 ) to follow a prospect i ve group treated with EWB as to long-term subjective and objective outcomes , and 2 ) to compare a subset of this group with a matched group of historic controls treated with 6WC . Design : Prospect i ve , clinical , cohort observation , and retrospective matched pair analysis . Setting : University hospital , level 1 trauma center . Patients : Forty-three patients ( 20 males ; mean age , 49 ± 14 years ) with operated Weber B/C fractures underwent EWB . For comparison , 23 patients of this group were matched to a same number of historic controls with respect to age , gender , body mass index , and fracture type . Intervention : Open reduction and internal fixation ( ORIF ) using a 1/3-tubular-fibula-plate for the fibula , and malleolar screws for the medial malleolus fracture ( in cases with a bimalleolar ankle fracture ) followed by EWB or 6WC . Main Outcome Measurements : Olerud and Tegner scores at follow-up ( at least 12 months after surgery ) , time to full weightbearing , return to work , pain intensity ( numerical rating scale ( NRS ) ) , and hospital stay . Statistical comparisons were performed by using the Mann-Whitney U test or Fisher exact test ( P < 0.05 ) . Results : Patients with EWB were full weightbearing at 7 ± 3 weeks and returned to work at 8 ± 5 weeks after surgery . At follow-up ( mean , 20 ± 11 months after surgery ) , all EWB patients showed good results in the Olerud score ( 90 ± 13 points ) . Matched-pair analysis in 23 patients in each group revealed differences between EWB and 6WC groups for hospital stay ( mean , 10.8 ± 4.7 vs. 13.6 ± 6 days ; P = 0.12 ) , time to full weightbearing ( mean , 7.7 ± 3.1 vs. 13.5 ± 9.4 weeks ; P = 0.01 ) , and time until return to work ( mean 9.2 ± 5.5 vs. 10.8 ± 7 weeks ; P = 0.63 ) . No differences concerning pain intensities were observed ( EWB vs. 6WC : NRS = 1.9 vs. 1.7 ; P = 0.12 ) . At follow-up , Olerud scores were generally considered good for both groups ; however , mean values in EWB patients were slightly higher ( 87 ± 14 vs. 79 ± 19 points ; P = 0.25 ) . In both groups , the majority of patients reached their preinjury level of activity as demonstrated by Tegner scores . Conclusions : EWB patients tolerated earlier full weightbearing compared with 6WC patients , and there were no disadvantages with EWB compared with 6WC concerning hospital stay , pain intensities , time until return to work , and Olerud/Tegner Scores . Potential c and i date s for EWB are patients with a stable osteo synthesis of their fractured ankles as judged by the responsible surgeon , compliance , and high motivation STUDY DESIGN Prospect i ve inception cohort study of 62 consecutive patients seen in 2 orthopaedic clinics following ankle fracture . OBJECTIVES To investigate 4 putative predictors ( age , fracture classification , acute management [ surgical or nonsurgical ] , and ankle dorsiflexion range of motion measured at the time of cast removal ) of outcome after ankle fracture and to develop simple predictive models of outcome after ankle fracture . BACKGROUND Ankle fracture is a common condition . However , few studies have investigated factors that predict outcome after ankle fracture . METHODS AND MEASURES Sixty-two consecutive subjects aged 17 or older with ankle fractures were recruited from 2 hospital orthopaedic clinics . Outcome measures recorded at 6 weeks and 6 months after cast removal included 2 functional question naires , patients ' ratings of global improvement , and a measure of ankle dorsiflexion . The predictive value of 4 variables selected a priori was analyzed using bivariate and stepwise multiple linear regression . RESULTS Ankle dorsiflexion and fracture classification predicted outcome 6 weeks and 6 months after cast removal for all outcome measures used ( P < .05 , r2 = 0.09 - 0.47 ) . Fracture management ( surgical or nonsurgical ) inconsistently predicted outcome at both 6 weeks and 6 months , and age did not predict outcome at either 6 weeks or 6 months after cast removal . The predictive models explain between 19 % and 58 % of the variance in outcomes 6 weeks after cast removal and 19 % to 52 % of the variance in outcomes 6 months after cast removal . CONCLUSION Ankle dorsiflexion measured at the time of cast removal and fracture classification are clinical ly significant predictors of outcome after ankle fracture ; however , much unexplained variation in outcomes still exists 40 patients with dislocated bimalleolar and trimalleolar ankle fractures took part in this r and omized study . All ankles were operated on using cerclage , staples and pins . Active ankle movement with weight bearing in an orthosis was compared with active ankle movement without weight bearing using a dorsal splint . Stereophotogrammetric analysis showed small movements in the ankle mortise in both groups but conventional radiography revealed no fracture redislocation . The clinical results did not differ . This study was design ed as the second part of a consecutive project . In the first part , early and late weight bearing in a cast without ankle movements was compared ( Ahl et al. 1987b ) . In comparing the first and the second parts of the study , a small but significant increase in fracture instability was observed in the early motion group . No lasting superior clinical result was achieved by early ankle movement . After operation on dislocated bimalleolar ankle fractures , early postoperative weight bearing in a walking cast is recommended Background Despite conflicting results after surgically treated ankle fractures few studies have evaluated the effects of different types of training programs performed after plaster removal . The aim of this study was to evaluate the effects of a 12-week st and ardised but individually suited training program ( training group ) versus usual care ( control group ) after plaster removal in adults with surgically treated ankle fractures . Methods In total , 110 men and women , 18 - 64 years of age , with surgically treated ankle fracture were included and r and omised to either a 12-week training program or to a control group . Six and twelve months after the injury the subjects were examined by the same physiotherapist who was blinded to the treatment group . The main outcome measure was the Olerud-Mol and er Ankle Score ( OMAS ) which rates symptoms and subjectively scored function . Secondary outcome measures were : quality of life ( SF-36 ) , timed walking tests , ankle mobility tests , muscle strength tests and radiological status . Results 52 patients were r and omised to the training group and 58 to the control group . Five patients dropped out before the six-month follow-up result ing in 50 patients in the training group and 55 in the control group . Nine patients dropped out between the six- and twelve-month follow-up result ing in 48 patients in both groups . When analysing the results in a mixed model analysis on repeated measures including interaction between age-group and treatment effect the training group demonstrated significantly improved results compared to the control group in subjects younger than 40 years of age regarding OMAS ( p = 0.028 ) , muscle strength in the plantar flexors ( p = 0.029 ) and dorsiflexors ( p = 0.030 ) . Conclusion The results of this study suggest that when adjusting for interaction between age-group and treatment effect the training model employed in this study was superior to usual care in patients under the age of 40 . However , as only three out of nine outcome measures showed a difference , the beneficial effect from an additional st and ardised individually suited training program can be expected to be limited . There is need for further studies to eluci date how a training program should be design ed to increase and optimise function in patients middle-aged or older . Trial Registration Current Controlled Trials OBJECTIVE The primary aim of this study was to determine the effectiveness and cost-effectiveness of adding manual therapy to a physiotherapy programme for ankle fracture . DESIGN Assessor-blinded r and omized controlled trial . PARTICIPANTS Ninety-four adults were recruited within one week of cast removal for isolated ankle fracture . Inclusion criteria were : they were able to weight-bear as tolerated or partial weight-bear , were referred for physiotherapy , and experienced pain . Ninety-one participants completed the study . METHODS Participants were r and omly allocated to receive manual therapy ( anterior-posterior joint mobilization over the talus ) plus a st and ard physiotherapy programme ( experimental ) , or the st and ard physiotherapy programme only ( control ) . They were assessed by a blinded assessor at baseline , and at 4 , 12 and 24 weeks . The main outcomes were activity limitation and quality of life . Information on costs and healthcare utilization was collected every 4 weeks up to 24 weeks . RESULTS There were no clinical ly worthwhile differences in activity limitation or quality of life between groups at any time-point . There was also no between-group difference in quality -adjusted life-years , but the experimental group incurred higher out-of-pocket costs ( mean between-group difference = AU$200 , 95 % confidence interval 26 - 432 ) . CONCLUSION When provided in addition to a physiotherapy programme , manual therapy did not enhance outcome in adults after ankle fracture In a prospect i ve , r and omized study , 30 patients were evaluated after ankle fracture treated by means of open reduction and internal fixation . The patients were r and omized to either postoperative immobilization in a plaster cast for 6 weeks or early mobilization ( 1–2 weeks after surgery ) in an ankle brace . Both regimens allowed weightbearing . Evaluation after 10 weeks and after 12 months included clinical assessment and isokinetic muscle strength measurements . Patients with impaired ankle function , as shown by means of an ankle score at 12 months , were followed for 3 years . At 10 weeks , impaired muscle torque and restricted range of motion was found on the affected side . This impairment was significantly less in the brace group . At 12 months , range of motion of the ankle and subtalar joints was restored , but dorsiflexion was still better in the brace group . Score values from a functional score did not correlate with muscle strength In a monocenter r and omized controlled trial , 45 patients with isolated malleolar fracture type OTA/AO 44 A1–B2 undergoing ORIF were allocated r and omly to a postoperative treatment either with a vacuum-stabilized orthesis with prescribed full weight bearing after the second week ( 23 patients ) ( orthesis group — OG ) or with functional aftertreatment with partial weight bearing of 15 kg for 6 weeks ( 22 patients ) ( control group — CG ) . Outcomes were compared at 6- and 10-week follow-up examinations . The Olerud and Mol and er ankle ( OMA ) score , ankle swelling , usage of crutches , range of motion , Short Form 12 , patient-reported visual analogue scales ( VAS ) ( pain , comfort , walking confidence ) and time to return to work were evaluated . All patients of OG showed reduced swelling at discharge . The median OMA scores after 6 weeks were 42 and 42.5 ( p = 0.46 ) and after 10 weeks 69 and 72 ( p = 0.55 ) in the OG and CG , respectively . The time to achieve secure walking capacity was reduced by 1 day ( p = 0.03 ) in the OG . After ORIF of simple malleolar fractures , patients with a vacuum-stabilized orthesis can bear full weight 2 weeks postoperatively . This group experienced no adverse events . Postoperative swelling was significantly reduced and of the ability to walk on stairs confidently was shorter as compared to a functional aftertreatment without any external stabilization of the ankle In the prospect i ve cohort study reported here , we used the Short Musculoskeletal Function Assessment ( SMFA ) question naire to assess rate of return of functional outcome after open reduction and internal fixation of unstable ankle fractures ( Orthopaedic Trauma Association/Arbeitsgemeinschaft für Osteosynthesefragen [ OTA/AO ] 44B and 44C ) at a level II trauma center over the course of 1 year . The entire group of 69 consecutive adults improved significantly ( P<.01 ) on the SMFA Emotional Status and Dysfunction scales from 2 to 4 months and on the Mobility and Daily Activities scales from 2 to 4 months and from 4 to 6 months . There were no significant changes on the Arm/H and Function and Bother scales . There was a significant effect of age on Mobility , Daily Activities , and Dysfunction , with older patients ( > or = 50 years ) obtaining higher ( worse ) scores . There was no significant effect on patient sex on any of the scales . Patients with 44C fractures ( vs 44B fractures ) had significantly ( P = .05 ) higher mean Bother scores at 6 months . There were no significant differences arising from presence or absence of a fracture of the medial malleolus . Our SMFA data show that older patients ( > or = 50 years ) and patients with 44C fractures had slower return to maximal function and higher Bother scores at 6 months . All groups reached a relatively stable functional outcome by 6 months after injury , but their mobility did not return to population norms over the same period Fifty-three patients with dislocated lateral malleolar fractures were r and omly selected after operation for either active ankle movement and weight bearing in an orthosis or no ankle movement but weight bearing in a walking cast . At follow-up examinations after three , six , and 18 months , no differences were found between the groups except for a better linear analogue scale result at three months for the orthosis group . Active ankle movements do not improve the rehabilitation of surgically treated lateral malleolar fractures BACKGROUND Ankle fractures are among the most common injuries treated by orthopaedic surgeons . However , very few investigators have examined the functional recovery following ankle fracture surgery and , to our knowledge , none have analyzed factors that may predict functional recovery . In this study , we evaluated predictors of short-term functional outcome following surgical stabilization of ankle fractures . METHODS Over three years , 232 patients who sustained a fracture of the ankle and were treated surgically were followed prospect ively , for a minimum of one year . Trained interviewers recorded baseline characteristics , including patient demographics , medical comorbidities , and functional status according to the Short Musculoskeletal Function Assessment ( SMFA ) . Laboratory findings , the American Society of Anesthesiologists ( ASA ) class , and operative findings were recorded from the chart during hospitalization . Follow-up information included the occurrence of complications or additional surgery , weight-bearing status , functional status according to the SMFA , and the American Orthopaedic Foot and Ankle Society ( AOFAS ) ankle-hindfoot score . The data were analyzed to determine predictors of functional recovery at three months , six months , and one year postoperatively . RESULTS Complete follow-up data were available for 198 patients ( 85 % ) . At one year , 174 ( 88 % ) of the patients had either no or mild ankle pain and 178 ( 90 % ) had either no limitations or limitations only in recreational activities . According to the AOFAS ankle-hindfoot score , 178 ( 90 % ) of the patients had > or = 90 % functional recovery . A patient age of less than forty years was a predictor of recovery , as measured with the SMFA subscores , at six months after the ankle fracture . At one year , however , age was no longer a predictor of recovery . Patients who were younger than forty were more likely to recover > or = 90 % of function ( p = 0.004 ) , and men were more likely than women to recover function ( p = 0.02 ) . ASA Class 1 or 2 ( p = 0.03 ) and an absence of diabetes ( p = 0.02 ) were also predictors of better functional recovery at one year . SMFA subscores were below average at baseline , indicating a healthy population . At three and six months postoperatively , all SMFA subscores were significantly higher than the baseline subscores ( p < 0.001 ) ; however , at one year , the SMFA subscores were almost back to the baseline , normal level . CONCLUSIONS One year after ankle fracture surgery , patients are generally doing well , with most experiencing little or mild pain and few restrictions in functional activities . They have a significant improvement in function compared with six months after the surgery . Younger age , male sex , absence of diabetes , and a lower ASA class are predictive of functional recovery at one year following ankle fracture surgery . It is important to counsel patients and their families regarding the expected functional recovery after an ankle injury BACKGROUND To our knowledge , no study to date has compared the use of spinal and general anesthesia in patients undergoing operative fixation of an unstable ankle fracture . The purpose of this study was to assess the effects of anesthesia type on postoperative pain and function in a large cohort of patients . METHODS Between October 2000 and November 2006 , 501 patients who underwent surgical fixation of an unstable ankle fracture were followed prospect ively . Patients receiving spinal anesthesia were compared with a cohort who received general anesthesia . All patients were evaluated at three , six , and twelve months postoperatively with use of st and ardized , vali date d general and limb-specific outcome instruments . St and ard and multivariable analyses comparing outcomes at these intervals were performed . RESULTS Four hundred and sixty-six patients ( 93 % ) who had been followed for a minimum of one year met the inclusion criteria . Compared with the general anesthesia group , the spinal anesthesia group had a greater mean age ( p = 0.005 ) , higher classification on the American Society of Anesthesiologists system ( p = 0.03 ) , and a greater number of patients with diabetes ( p = 0.02 ) . There was no difference in sex distribution between the groups . At three months , patients who received spinal anesthesia had significantly better pain scores ( p = 0.03 ) and total scores on the American Orthopaedic Foot and Ankle Society outcome instrument ( p = 0.02 ) . At six months , patients in the spinal anesthesia group continued to have better pain scores ( p = 0.04 ) , but there was no longer a difference in total scores ( p = 0.06 ) . At twelve months , no difference was detected between the groups in terms of functional or pain scores . There was no difference in complication rates between the groups . CONCLUSIONS Patients who undergo fixation of an ankle fracture under spinal anesthesia seem to experience less pain and have better function in the early postoperative period . We recommend that , unless there is a specific contraindication , patients should be offered spinal anesthesia when undergoing operative fixation of an ankle fracture Objective : To assess short-term functional results in 2 types of syn-desmotic fixation , comparing the traditional rigid quadricortical syndesmotic screw fixation with a more dynamic tricortical screw fixation . Design : Prospect i ve , r and omized clinical study . Setting : University clinic , level 1 trauma center . Patients : Sixty-four patients with closed ankle fractures in which the syndesmosis was found to be unstable intraoperatively . Intervention : The unstable syndesmoses were fixed with either one 4.5-mm cortical screw through both tibial cortices ( n = 30 ) or two 3.5-mm cortical screws engaging only 1 cortex of the tibia ( n = 34 ) . The quadricortical screws were routinely removed after 2 months , whereas the tricortical screws were removed only in the case of discomfort . Rehabilitation was the same in both groups . Results : The Olerud Mol and er functional score ( 0–100 ) was significantly higher in the tricortical group ( 77 points ) compared with the quadricortical group ( 66 points ) ( P = 0.025 ) at 3 months . After 1 year , however , the functional score was not significantly higher ( P = 0.192 ) in the tricortical group ( 92.6 points ) compared with the quadricortical group ( 85.7 points ) . Pain was significantly lower in the tricortical group ( P = 0.017 ) after 3 months , but there was no significant difference after 1 year . There was no significant difference in dorsiflexion between the groups at any point of time . No losses of fixation were detected . The tricortical screws were removed in 2 patients due to migration . Conclusions : Syndesmosis fixation with 2 tricortical screws is safe and improves early function . After 1 year , however , there were no significant differences between the 2 groups in functional score , pain , and dorsiflexion OBJECTIVE To compare the efficacy of short- and long- duration passive stretches with a control treatment for the management of plantarflexion contracture after cast immobilization for ankle fracture . DESIGN Assessor-blinded , r and omized controlled trial . SETTING Hospital physical therapy outpatient departments . PARTICIPANTS Adults with plantarflexion contracture ( N=150 ) after cast immobilization for ankle fracture . All subjects were weight bearing or partial weight bearing . INTERVENTIONS Exercise only , exercise plus short- duration passive stretch , and exercise plus long- duration passive stretch . All subjects had a 4-week course of exercises . In addition , subjects in the short- duration stretch plus exercise group completed 6 minutes of stretching per day , and subjects in the long- duration stretch plus exercise group completed 30 minutes of stretching per day . MAIN OUTCOME MEASURES Lower Extremity Functional Scale and passive dorsiflexion range of motion with the knee bent and straight at baseline , and at 4 weeks and 3 months postintervention . RESULTS One hundred thirty-nine ( 93 % ) subjects completed the 4-week assessment and 134 ( 89 % ) subjects completed the 3-month assessment . There were no statistically significant or clinical ly important between-group differences for the primary outcomes . CONCLUSIONS The addition of passive stretching confers no benefit over exercise alone for the treatment of plantarflexion contracture after cast immobilization for ankle fracture BACKGROUND AND PURPOSE The goal of this investigation was to study the recovery of ankle plantar-flexor peak torque , fatigue resistance , and functional ability ( stair climbing , walking ) following cast immobilization in patients with ankle fractures . SUBJECTS The participants were 10 patients who underwent open reduction-internal fixation and 8 weeks of cast immobilization following a fracture of the ankle mortise and 10 age- and sex-matched , noninjured comparison subjects . METHODS Plantar-flexor torque and fatigue resistance were measured at 1 , 5 , and 10 weeks of rehabilitation using an isokinetic dynamometer . Ankle plantar-flexor peak torque and fatigue resistance were correlated to timed ambulation , timed stair climbing , and unilateral heel-rises . RESULTS Following immobilization , plantar-flexor peak torque was decreased at all angular speeds and positions . The decrease in peak torque was associated with an increase in fatigue resistance . With rehabilitation , ankle plantar-flexor torque and fatigue resistance normalized . Regression analysis revealed a strong relationship between plantar-flexor peak torque and functional measures . By 10 weeks post-immobilization , peak torque , fatigue resistance , and all measures of functional performance had returned to control levels . CONCLUSION AND DISCUSSION The decrease in muscle performance , functional ability , and fatigue resistance induced by 8 weeks of cast immobilization can be reversed with 10 weeks of supervised physical therapy . In addition , this study demonstrated that ankle-plantar flexor torque is a good predictor of stair-climbing and walking performance in patients with ankle fractures Objective : This study was performed to evaluate the results of operative treatment of ankle fractures in patients who required syndesmotic stabilization in addition to malleolar fracture fixation compared with patients who required malleolar fixation alone . Design : The authors conducted a retrospective review of prospect ively collected data . Setting : Academic medical center . Patients : Between October 2000 and November 2006 , 347 patients who underwent surgical repair of an unstable ankle fracture were enrolled in a prospect i ve data base . Intervention : Patients who had an associated syndesmotic disruption requiring surgical stabilization in association with either an ankle fracture or a fracture-dislocation were identified and compared with a cohort treated during the same time period who had sustained an ankle fracture or fracture-dislocation without syndesmotic disruption . Main Outcome Measurements : All patients were followed and evaluated at 3 , 6 , and 12 months with clinical and radiographic examination as well as functional status ( Short Musculoskeletal Functional Assessment , American Orthopaedic Foot and Ankle Society ) . Patient-reported pain and postoperative complications were recorded as well . Results : Three hundred forty-seven patients met the inclusion criteria and had 1-year minimum follow up . Seventy-nine patients ( 23 % ) who had syndesmotic stabilization were identified and compared with 268 patients ( 77 % ) who did not . No differences were found between the two groups with respect to age or American Society of Anesthesiologists status ; however , there was a greater percentage of men in the syndesmotic injury group ( P = 0.04 ) . There was a greater percentage of Type C fractures requiring syndesmosis stabilization , whereas Type B fractures were less likely to require syndesmosis stabilization ( P = 0.001 ) At 6- and 12-month follow up , there was a clear difference in outcome based on American Orthopaedic Foot and Ankle Society and Short Musculoskeletal Functional Assessment scores ; patients who underwent syndesmotic stabilization had worse American Orthopaedic Foot and Ankle Society scores with lower function ratings ( P = 0.04 ) and worse pain ratings ( P = 0.02 ) . Short Musculoskeletal Functional Assessment scores were also worse at 12 months in patients who had syndesmotic stabilization because the dysfunction index was higher in the syndesmotic injury group ( P = 0.009 ) . Radiographically , 18 of 144 ( 13 % ) syndesmotic screws were noted to be broken on follow-up radiographs , eight of which were subsequently removed . There were no other differences in complication rates . Conclusion : Patients who required syndesmotic stabilization in addition to malleolar fracture fixation had poorer outcomes at 12 months compared with patients who required malleolar fracture fixation alone . This information is important for patient counseling to manage expectations regarding outcomes after injury Background and Aims : The present study was initiated to evaluate the long-term effects of low-intensity ultrasound therapy on bioabsorbable screw-fixed lateral malleolar fractures , which has not been studied earlier . Patients and Methods : The study design was prospect i ve , r and omized , double-blinded , and placebo-controlled . Sixteen dislocated lateral malleolar fractures were fixed with one bioabsorbable self-reinforced poly-L-lactide screw . The patients used an ultrasound device 20 minutes daily for six weeks without knowing it was active ( eight patients ) or inactive ( eight patients ) . The follow-up time was 18 months . The radiological bone morphology was assessed by multidetector computed tomography ( MDCT ) scans , the bone mineral density by dual-energy X-ray absorptiometry scans , and the clinical outcome by Olerud-Mol and er scoring and clinical examination of the ankle . Results : The MDCT scans revealed that all fractures were fully healed , and no differences were observed in radiological bone morphology at the fracture site . The bone mineral density of the fractured lateral malleolus tended to increase slightly during the 18-month follow-up , the increase being symmetrical in both groups . No differences were observed in the clinical outcome or Olerud-Mol and er scores . Conclusions : The six-week low-intensity ultrasound therapy had no effect on radiological bone morphology , bone mineral density or clinical outcome in bioabsorbable screw-fixed lateral malleolar fractures 18 months after the injury Background : The aim of operative treatment for ankle fractures is to allow early movement after internal fixation . The hypothesis of this study was that early mobilization would improve functional recovery in patients after surgery for ankle fractures . Methods : In a prospect i ve r and omized controlled study , 66 consecutive patients with ankle fractures that required open reduction and internal fixation ( ORIF ) were assigned to one of two postoperative regimens : immobilization in a nonweightbearing below-knee cast or early mobilization in a removable cast . Four patients were excluded from the study , leaving 62 for review . Results : Patients who had early mobilization in a removable cast had higher functional scores ( Olerud-Mol and er and AOFAS ) at 9 and 12 weeks postoperatively . They also returned to work earlier ( 67 days ) compared with those treated in nonweightbearing below-knee cast ( 95 days ) , p < 0.05 . There was no statistical difference in Quality of Life ( SF-36 Question naire ) at 6 months between the two groups . We had an approximately 10 % postoperative infection trend ( one superficial and two deep ) in the early mobilization group . Conclusion : Despite the overall short-term benefit of early mobilization , we had three patients in the early mobilization group who had wound complications . Both the surgeon and patient should be aware of the higher risk of wound complications associated with this treatment , and thus the accelerated rehabilitation protocol should be individualized Background : Controversy continues with regard to the optimal postoperative care after open reduction and internal fixation of an ankle fracture . The hypothesis of this study was that postoperative treatment of an ankle fracture with a brace that allows active and passive range-of-motion exercises would improve the functional recovery of patients compared with that after conventional treatment with a cast . Thus , the purpose of this prospect i ve , r and omized study was to compare the long-term subjective , objective , and functional outcome after conventional treatment with a cast and that after use of functional bracing in the first six weeks following internal fixation of an ankle fracture . Methods : One hundred patients with an unstable and /or displaced Weber type-A or B ankle fracture were treated operatively and then were r and omly allocated to two groups : immobilization in a below-the-knee cast ( fifty patients ) or early mobilization in a functional ankle brace ( fifty patients ) for the first six postoperative weeks . The follow-up examinations , which consisted of subjective and objective ( clinical , radiographic , and functional ) evaluations , were performed at two , six , twelve , and fifty-two weeks and at two years postoperatively . Results : There were no perioperative complications in either study group , but eight patients who were managed with a cast and thirty-three patients who were managed with a brace had postoperative complications , which were mainly related to wound-healing . Two patients in the group treated with a cast had deep-vein thrombosis . All fractures healed well in both groups . The difference between the two groups with respect to the complication rate was significant ( p = 0.0005 ) . No significant differences between the study groups were observed in the final subjective or objective ( clinical ) evaluation . At the two-year follow-up examination , the average score ( and st and ard deviation ) according to the ankle-rating scale of Kaikkonen et al. was 85 ± 9 points for the group treated with a cast and 83 ± 10 points for the group treated with a brace , and the average ankle score according to the system of Olerud and Mol and er was 87 ± 8 points and 87 ± 9 points , respectively . Conclusions : The long-term functional outcome after postoperative treatment of an ankle fracture with a cast and that after use of a functional brace are similar . Although early mobilization with use of a functional ankle brace may have some theoretical beneficial effects , the risk of postoperative wound complications associated with this treatment approach is considerably increased compared with that after conventional cast treatment . Thus , the postoperative protocol of treatment with a functional brace requires refinement before it can be generally advocated for use after operative treatment of an ankle fracture . Level of Evidence : Therapeutic study , Level I-1b ( r and omized controlled trial [ no significant difference but narrow confidence intervals ] ) . See Intructions to Authors for a complete description of levels of evidence Background : Although Weber type B ankle fractures are often considered benign with a good prognosis , evidence from observational studies suggests that 17 % to 24 % of such patients may have less satisfactory outcomes . Although the explanation for variability in outcomes remains unclear , previous studies of other surgical procedures have suggested nonsurgery-related causes account for much of the variability in outcomes . Methods : We conducted a prospect i ve observational cohort study to evaluate health-related quality of life in 30 patients with unstable ankle fractures who were otherwise healthy . Only patients from 2 university-affiliated hospitals sustaining unstable type B Weber injury patterns requiring surgery were eligible . Patients provided detailed baseline information regarding alcohol consumption , smoking habits , and educational level . Patients completed the short form 36 question naire and a visual analogue pain scale at regular follow-up intervals . Results : The average patient age was 51.6 years ( SD 15.2 years ) , and 57 % ( 17 out of 30 ) were male . The majority of fractures were the result of a fall ( 67 % , 20 out of 30 ) , and all were closed injuries . Almost half of all patients were smokers ( 47 % , 14 out of 30 ) , whereas 43 % consumed alcohol on a weekly basis ( 13 out of 30 ) . Forty-three percent of patients ( 13 out of 30 ) had obtained an elementary or high school level of education . Patients experienced significant improvements in all domains of the SF-36 question naire ( P < 0.001 ) , except general health , which remained essentially normal over the 24-month period . Study patients achieved scores similar to age-matched U.S. normative data across 6 of the 8 domains ( Role Emotional , Social Function , Mental Health , Bodily Pain , Vitality , and General Health ) . However , patients ’ physical function and role physical scores remained significantly lower than US norms at 24 months ( 21.8 and 20.7 points lower on a 100-point scale , respectively ; P < 0.001 ) . Smoking history ( P = 0.02 ) , presence of a medial malleolar fracture ( P = 0.02 ) , and lower levels of education ( P = 0.01 ) were significant independent predictors of lower physical function up to 3 months postoperation . Lower mental health domain scores were significantly associated with alcohol use ( P = 0.02 ) and increasing age ( P = 0.04 ) . Conclusions : As is the case in many other areas , social factors may be important determinants of outcome in patients with traumatic fractures . Optimal orthopedic care may involve attention to modifiable risk factors , including smoking and alcohol consumption We performed a prospect i ve r and omized study comparing fixation with biodegradable polyglycolic acid ( PGA ) rods ( n 15 ) or screws ( n 17 ) in 32 selected displaced supination-eversion fractures . Immediate postoperative weight bearing in a walking cast was encouraged . An exact reconstruction of the ankle mortise was achieved in 26/32 ankles . Roentgen stereophotogrammetric analysis ( RSA ) revealed rather small movements in the ankle mortise during fracture healing . A better stability was achieved by using screws . After 6 months the clinical results did not differ . One case of sinus formation and one with local effusion occurred ; both healed without impairing the clinical result . To compare the results with a nondegradable osteo synthesis technique , a reference group of supination-eversion fractures previously operated on with cerclage-wires , staples and pins was used . RSA showed better fracture stability with nondegradable fixation . The clinical results , however , did not differ Objectives : To compare clinical and functional outcomes after operative and nonoperative treatment of undisplaced , unstable , isolated fibula fractures . Design : R and omized multicenter clinical trial . Setting : Six level 1 trauma centers . Patients / Participants : Eighty-one patients with undisplaced , unstable , isolated fibula fractures as confirmed by an external rotation stress examination demonstrating an increase in medial clear space to 5 mm or greater were followed for 12 months after treatment . Intervention : Forty-one patients were treated operatively by open reduction and internal fixation of the fibula . Forty patients underwent nonoperative treatment , which included the use of a short leg cast or brace and protected weight bearing for 6 weeks . Main Outcome Measurements : Functional outcomes determined using the Olerud – Mol and er Ankle Score and the Short Form 36 . Radiographic outcomes included measurement of union and displacement at each visit . Results : There were no statistically significant differences in functional outcome scores or pace of recovery between the operative and nonoperative groups at any time interval ( & bgr ; = −0.28 , 3.49 ; P = 0.936 ) . Complications in the nonoperative group included 8 patients with a medial clear space ≥5 mm and 8 patients with delayed union or nonunion . In the operative group , 5 patients had a surgical site infection and 5 patients required hardware removal . Conclusions : Patients managed operatively had equivalent functional outcomes compared with nonoperative treatment ; however , the risk of displacement and problems with union was substantially lower in patients managed with surgery Background : The goal of this review was to compare the functional outcomes of patients less than 60 and greater than or equal to 60 years old following operative stabilization of unstable ankle fractures . The review was conducted as a retrospective analysis of prospect ively collected data at two level one trauma centers and a tertiary referral academic center . Material s and Methods : All patients operatively treated for an unstable ankle fracture were entered into a data base and prospect ively followed . The postoperative protocol was st and ardized for all patients . Baseline characteristics , complications , additional surgery , functional status and the American Orthopaedic Foot and Ankle Society score ( AOFAS ) were assessed . The intervention chosen was open reduction and internal fixation of unstable ankle fractures . AOFAS hindfoot score and Short Musculoskeletal Functional Assessment ( SMFA ) question naire were used as the main outcome measures in the study . A p < 0.05 was considered significant . Results : Three hundred sixty-nine ( 369 ) patients were entered into the data base , 313 ( 84.8 % ) were less than 60 years old . At 3 months , 57 % ( 32/56 ) of patients greater than or equal to 60 years old reported limitation of activities versus 33 % ( 103/313 ) of patients less than 60 years old ( p = 0.005 ) . At 6 and 12 months , these percentages improved to 41 % versus 10 % ( p = 0.001 ) , and 29 % versus 7.4 % ( p = 0.001 ) for older and younger individuals respectively . However , when compared to their baseline scores , both groups achieved a return to pre-injury status . Total AOFAS scores were not significantly different at 3 , 6 , or 12 months ( p = 0.431 ) . Conclusion : Operative fixation of unstable ankle fractures in patients greater than or equal to 60 years old can provide a reasonable functional result at the 1-year followup with a return to preoperative baseline even though they report more limitation of activities than younger patients BACKGROUND Biodegradable devices have been developed to overcome the disadvantages of metallic implants especially the need for their subsequent removal , though they have their own drawbacks like poor mechanical properties and tissue reactions . Aim of this prospect i ve study was to access the outcome of bimalleolar fractures fixed with biodegradable plates and screws . METHODS A prospect i ve study was conducted between July 2006 and November 2008 comprising of sixteen patients with unilateral bimalleolar fractures . Fibula fractures were fixed with biodegradable plates and medial malleoli with screws . Patients were followed at two weeks , six weeks , three months , six months , twelve months and eighteen months . Final evaluation was done using Olerud Mol and er ankle score . RESULTS Six patients had excellent results ; four patients had good results and six patients had fair performance . No patient in this series had a poor outcome . One patient had both pain and swelling at 14 weeks postoperatively which settled down with debridement and antibiotics . None of the patients needed implant removal . CONCLUSION Biodegradable plates and screws when used to fix bimalleolar fracture along with restricted weight bearing , provide satisfactory fracture healing , good functional results and reduce the need of implant removal A prospect i ve r and omized investigation of early versus late weight bearing in 46 patients with fracture of the lateral malleolus was performed . In 43/46 patients an exact operative reconstruction of the ankle mortise could be achieved using pins , staples and cerclage ( Cedell , 1967 ) . Radiographic and stereophotogrammetric analysis of the ankles after 3 months showed no significant differences , nor did the clinical follow-up Stable lateral malleolar fractures can be treated with dynamic braces and early mobilization . In a r and omized clinical trial , 66 patients with supination-eversion stage II fractures were treated with Aircast Air-Stirrup ankle braces or DonJoy R.O.M.-Walker braces . Average bracing time was 5 weeks , and average time until return to work was 6 weeks . At 4 weeks , 70 % to 80 % of patients were able to walk without pain . Subjective satisfaction with comfort and ease of use was significantly higher with Aircast , although it was high in both groups . Pain relief and an inflammatory score were significantly better in the R.O.M.-Walker group after 4 weeks . Three months after injury , no differences were observed in grade of ambulation , pain , swelling , range of motion , or inflammatory score . Both braces can be recommended A prospect i ve r and omized study was performed comparing immediate and late weight bearing in 53 dislocated bimalleolar and trimalleolar fractures . Using cerlage , staples , and pins ( Cedell 1967 ) , an exact reconstruction of the ankle mortise was achieved in 41/53 ankles . At follow-up after 3 and 6 months , the two groups were equal regarding clinical results . Evaluation radiographically and by roentgen stereophotogrammetric analysis ( Selvik 1974 ) indicated that the stability of the ankle mortise was sufficient to allow early postoperative weight bearing Sixty-one active-duty military personnel with operatively treated ankle fractures were r and omized into two postoperative immobilization regimens : Group I -- six weeks short-leg cast , nonweight-bearing ; Group II -- six weeks removable orthosis , nonweightbearing . Group I began physical therapy at six weeks postoperatively , and Group II began physical therapy within the first postoperative week . Objective measurements of swelling , strength , range of motion , and functional tests were examined . Subjective scores of pain , function , cosmesis , and motion were recorded . Patients in Group II ( early mobilization ) had significantly better subjective scores at three and six months postoperatively ; however , time to return to duty was not significantly different . Objective tests of swelling , strength , range of motion , and functional tests were not significantly different at three months postoperatively for either group . Early mobilization in a removable orthosis , while not objective ly altering the postoperative course , provides a safe , preferable method of treatment in the reliable and cooperative patient |
758 | 25,517,473 | AUTHORS ' CONCLUSIONS GCS are effective in diminishing the risk of DVT in hospitalised patients , with strong evidence favouring their use in general and orthopaedic surgery . | BACKGROUND One of the setting s where deep vein thrombosis ( DVT ) in the lower limb and pelvic veins occurs is in hospital with prolonged immobilisation of patients for various surgical and medical illnesses .
Using graduated compression stockings ( GCS ) in these patients has been proposed to decrease the risk of DVT .
This is an up date of a Cochrane review first published in 2000 and up date d in 2010 .
OBJECTIVES To evaluate the effectiveness and safety of graduated compression stockings in preventing DVT in various groups of hospitalised patients . | BACKGROUND Venous thromboembolism is known to be an important social and health care problem because of its high incidence among patients who undergo surgery . Studies on the mechanical prophylaxis of thromboembolism after gynaecological pelvic surgery are few . The aim of our study was to evaluate the effect of mechanical thromboembolism prophylaxis after gynaecological pelvic surgery using a combination of graduated compression stockings ( GCS ) and intermittent pneumatic compression ( IPC ) or GCS alone . METHODS The study was performed on 108 patients who were r and omly assigned to two groups . The first group received GCS before the operation and IPC during the operation ( IPC + GCS group ) . The second group received GCS before the operation ( GCS group ) . To analyze the effect of the preventive measures and the laboratory examination on the incidence of thrombosis and to compare the safety of these measures , the incidence of adverse reactions was assessed . RESULTS The morbidity associated with DVT was 4.8 % ( 5/104 ) in the IPC + GCS group and 12.5 % ( 14/112 ) in the GCS group . There were significant statistical differences between the two groups . There were no adverse effects in either group . CONCLUSIONS The therapeutic combination of GCS and IPC was more effective than GCS alone for thrombosis prevention in high-risk patients undergoing gynaecological pelvic surgery , and there were no adverse effects in either group We studied 80 patients who were older than 50 years of age to determine if grade d elastic compression stockings reduced the frequency of postoperative thrombosis in patients undergoing dextran 70 prophylaxis . All of the patients received a total of 2,000 mL of dextran 70 during three days ; according to a r and om table , each of the patients had one leg encased in a grade d compression stocking for one week . Thrombosis development was screened with the fibrinogen I 125 test . Eight patients manifested thrombosis-one in the thigh and seven in the calf -- localized to the unstockinged leg , a frequency significantly greater than the zero frequency in the stockinged leg . No untoward effects of this combination prophylaxis were noted INTRODUCTION Darexaban ( YM150 ) is an oral direct factor Xa inhibitor in clinical development for prophylaxis of venous thromboembolism ( VTE ) after major orthopaedic surgery . The objective of this study was to assess the efficacy and safety of darexaban 15 mg twice daily ( bid ) in Japanese patients undergoing major abdominal surgery . MATERIAL S AND METHODS In a Phase III , multicentre , r and omized , open-label , mechanical prophylaxis-controlled , parallel-group study , adult patients ( aged ≥ 40 years ) were r and omized to darexaban 15 mg bid or mechanical prophylaxis , for 28 days . The primary efficacy outcome was incidence of total VTE at Day 12 . Adverse events ( AEs ) and bleeding events were recorded throughout the study . RESULTS The total VTE incidence at Day 12 was 2.6 % in the darexaban 15 mg bid group ( 95 % confidence interval [ CI ] : 0.32 , 9.07 ) , compared with 15.0 % ( 95 % CI : 5.71 , 29.84 ) in the mechanical prophylaxis group . During the investigational period , the incidence of all bleeding events was 9.5 % in the darexaban 15 mg bid group and 3.9 % in the mechanical prophylaxis group . In the darexaban 15 mg bid group , one patient experienced major bleeding and five patients experienced clinical ly relevant non-major ( CRNM ) bleeding . No patients in the mechanical prophylaxis group experienced major and /or CRNM bleeding . AEs were reported in 71.4 % of patients in the darexaban 15 mg bid group and 76.5 % of patients in the mechanical prophylaxis group ; the most frequent AEs across both treatment groups were constipation and insomnia . No patients died during the study . CONCLUSIONS Based on these findings , darexaban is expected to be effective for the prevention of VTE in patients undergoing major abdominal surgery . ( CLINICAL TRIAL REGISTRATION NUMBER NCT00942435 ) A study of 95 patients determined the incidence of postoperative venous thrombosis and the effectiveness of simple prophylactic measures . In addition , the accuracy of the radioactive fibrinogen technique for the detection of thrombosis was compared to venography . Deep venous thrombosis was detected in six of 44 ( 14 % ) control patients . However , only two of 51 ( 4 % ) patients on whom prophylactic measures were applied developed thrombosis . The ages of the patients with thrombosis occurring postoperatively were significantly higher than the ages of the other patients in this study . There was an excellent correlation of the results obtained by the radioactive method with those of venography . Laboratory tests indicated a deficient endogenous fibrinolytic activity in those patients who developed thrombosis The effect of incremental increases in external pressure , applied to the leg , on blood volume flow in the femoral vein was studied in dogs . Clinical investigation of external pressure increases was also carried out on nine patients undergoing surgery for varicose veins . An external pressure between 5 and 15 mm . Hg caused a sustained increase in mean femoral vein flow both in a control and in the compressed limb . Above 15 mm . Hg external pressure flow decreased in the compressed limb but was maintained at an increased level in the control limb . If external compression is to be used to prevent and treat deep vein thrombosis its application must be carefully controlled Lower‐limb venous haemodynamics were studied prospect ively in 40 patients ( 24 women , 16 men of median age 52 years ) undergoing laparoscopic cholecystectomy . Patients were r and omized to wear compression stockings during surgery or no stockings . All received subcutaneous heparin prophylaxis . Venous capacitance and outflow were measured non‐invasively before , during and after pneumo‐peritoneum . In the group without compression stockings ( 20 patients ) venous capacitance and outflow decreased during pneumoperitoneum in most patients . In the group wearing stockings ( 20 patients ) the changes were less pronounced or abolished . There was a significant difference between the groups in venous capacitance and outflow ratios at mid‐operation : median ( interquartile range ) 0‐89 ( 0‐56‐1‐16 ) and 0‐89 ( 0‐56‐1‐15 ) respectively in the group without stockings versus 1‐48 ( 1‐09‐2‐19 ) and 1‐71 ( 1‐20‐2‐19 ) respectively in that with stockings ( P < 0.001 ) . Pneumoperitoneum creates a significant resistance to venous return . Compression stockings counteract the changes observed In a prospect i ve , r and omized study on 114 patients undergoing major abdominal surgery , the prophylactic effect of dihydroergotamine ( DHE ) combined with low-dose heparin ( LDH ) against postoperative deep vein thrombosis ( DVT ) was compared with that of peroperative intermittent pneumatic calf compression ( IPCC ) . The additive effect of graduated pressure stockings was also studied , by r and omizing a stocking to the right or left leg in each patient . The 125I-fibrinogen test was used to diagnose DVT . The incidence of postoperative DVT was significantly lower in the DHE-LDH than in the IPCC group ( 4 % v. 19 % ) . In the IPCC group the incidence of postoperative DVT was equal in legs with and without stocking . The study thus indicated that DHE-LDH is more effective than peroperative IPCC in preventing DVT after major abdominal surgery , and that graduated pressure stockings do not enhance the prophylactic effect of peroperative IPCC Purpose Venous thromboembolism ( VTE ) is a frequent and serious problem in intensive care units ( ICU ) . Anticoagulant treatments have demonstrated their efficacy in preventing VTE . However , when the bleeding risk is high , they are contraindicated , and mechanical devices are recommended . To date , mechanical prophylaxis has not been rigorously evaluated in any trials in ICU patients . Methods In this multicenter , open-label , r and omized trial with blinded evaluation of endpoints , we r and omly assigned 407 patients with a high risk of bleeding to receive intermittent pneumatic compression ( IPC ) associated with graduated compression stockings ( GCS ) or GCS alone for 6 days during their ICU stay . The primary endpoint was the occurrence of a VTE between days 1 and 6 , including nonfatal symptomatic documented VTE , or death due to a pulmonary embolism , or asymptomatic deep vein thrombosis detected by ultrasonography systematic ally performed on day 6 . Results The primary outcome was assessed in 363 patients ( 89.2 % ) . By day 6 , the incidence of the primary outcome was 5.6 % ( 10 of 179 patients ) in the IPC + GCS group and 9.2 % ( 17 of 184 patients ) in the GCS group ( relative risk 0.60 ; 95 % confidence interval 0.28–1.28 ; p = 0.19 ) . Tolerance of IPC was poor in only 12 patients ( 6.0 % ) . No intergroup difference in mortality rate was observed . Conclusions With the limitation of a low statistical power , our results do not support the superiority of the combination of IPC + GCS compared to GCS alone to prevent VTE in ICU patients at high risk of bleeding Totally , 150 patients , subjected to total hip arthroplasty , were r and omly allocated into three prophylactic groups with either conventional dextran alone or with additional grade d compression stockings or with additional preoperative administration of dextran . The overall frequency of deep venous thrombosis ( DVT ) , as studied by radioactive fibrinogen uptake test and ascending phlebography of the operated on thigh was in the conventional dextran group 46 percent , the additional stockinged group 30 percent , and in the additional preoperative dextran group 52 percent . In the stockinged group , there was a lower frequency of DVT in the nonoperated on leg as well as , on an average , about 350 mL less peroperative bleeding as compared with the other two groups . No adverse reaction occurred from dextran administration . Increased and prolonged postoperative administration of dextran decrease the number of femoral DVTs Postoperative thromboembolic complications were evaluated in 2578 patients undergoing elective abdominal surgery , all receiving prophylaxis with low molecular weight heparin . A positive fibrinogen uptake test ( FUT ) developed in 217 patients ( 8.4 % ) , while 37 patients ( 1.4 % ) had major thromboembolism ( TE , defined as proximal deep vein thrombosis and /or pulmonary embolism , verified with phlebography , pulmonary scintigraphy or autopsy ) . In only 14 % a positive FUT was associated with a major TE event . In 19 % of the patients with major TE the FUT was negative . In multiple logistic regression the independent predictors for major TE were partially different from those for positive FUT . Thirty day mortality was 3.0 % . There were significant associations between both positive FUT and major TE on one h and and mortality on the other ( relative risks 2.4 and 5.8 , respectively ) . FUT is not a good predictor of major TE . Both positive FUT and major TE indicate a significant risk of postoperative death Seventy-eight patients having elective total hip replacement were r and omised into 3 groups A ) control ; B ) low molecular weight heparin : ( enoxaparin 40 mg once daily ) and C ) enoxaparin ( 40 mg once daily ) plus graduated elastic compression ( TEDR stockings ) for 8 - 12 days . All patients had a preoperative perfusion lung scan and chest X-Ray and a postoperative perfusion/ventilation scan together with bilateral ascending venography on days 8 - 12 . A blood sample was taken preoperatively , on the 1st , 3rd and 5th postoperative day and at the end of the study . The control group received placebo injections . The venograms and V/Q scans were reported blindly by an independent panel of three and one radiologists respectively . An independent panel of assessors stopped entry in the control group when a total of 45 patients were admitted according to Ethics Committee directives . The study continued with groups B and C. The incidence of DVT ( including isolated asymptomatic calf thrombi ) was as follows : Group A ( n = 14 ) 93 % ; Group B ( n = 32 ) 38 % ; Group C ( n = 32 ) 25 % ( chi 2 ; p < 0.001 for group A versus B or C ) . The incidence of proximal DVT was : Group A 57 % ; group B 28 % ; group C 13 % ( chi 2 ; p = 0.057 for group A versus B and p < 0.005 for group A versus C ) . The incidence of silent pulmonary embolism ( PE ) ( new defect on V/Q scan ) was 28 % ( 8 out of 29 ) in patients with and 5 % ( 2 out of 43 ) in patients without DVT ( chi 2 ; p < 0.02 ) . The combination of high TAT and low anti-Xa activity on the 1st postoperative day identified a high risk group of patients who had a 56 % incidence of proximal DVT on the 8th to 12th postoperative day . Further studies are needed to confirm the suggested increased efficacy in prophylaxis by the combination of LMWH and GEC as compared with LMWH alone PURPOSE This study was done to evaluate the mean venous velocity ( MVV ) response with knee and thigh length compression stockings ( CS ) versus intermittent pneumatic compression ( IPC ) devices in immobile patients with brain injuries . METHODS We carried out a r and omized controlled study . We analyzed both legs of a r and omly chosen sample of 43 patients assigned to one of 4 groups ( 86 legs ) . The patients were sequentially hospitalized in the intensive care unit ( ICU ) in " S hospital " from November 2005 to December 2006 . The base line and augmented venous velocity was measured at the level of the common femoral vein . We applied leg compression 42 times over 7 days ( for 2 hours at a time at 2 hour intervals ) . RESULTS There was a statistical difference among the 4 groups . The difference for the " IPC " group was more significant than the " CS " group . CONCLUSION These results indicate that the application of IPC can be considered as an effective method to prevent deep vein thrombosis for immobile patients with brain injury BACKGROUND Patients undergoing neurosurgical procedures are at risk of venous thromboembolism ( VTE ) , but often have contraindications for anticoagulant prophylaxis . OBJECTIVES To assess the efficacy and tolerability of a new , lightweight , portable , battery-powered , intermittent calf compression device , Venowave , for the prevention of VTE in neurosurgical in patients . PATIENTS / METHODS We performed an open r and omized controlled trial comparing Venowave with control for the prevention of VTE in patients undergoing neurosurgery . The primary outcome was the composite of asymptomatic deep vein thrombosis ( DVT ) detected by screening venography or compression ultrasound performed on day 9 ( ± 2 days ) and symptomatic VTE . RESULTS We r and omized 75 patients to receive Venowave devices and 75 to the control group . All patients were prescribed graduated compression stockings and physiotherapy . VTE occurred in three patients r and omized to Venowave and in 14 patients r and omized to control ( 4.0 % vs. 18.7 % , relative risk 0.21 ; 95 % confidence interval 0.05 - 0.75 , P = 0.008 ) . Similar reductions were seen for proximal DVT ( 2.7 % vs. 8.0 % ) and symptomatic VTE ( 0 % vs. 2.7 % ) , and the results were consistent in all subgroups examined . CONCLUSIONS Venowave devices are effective in preventing VTE in high-risk neurosurgical patients Background Half of all lower limb deep vein thrombi ( DVT ) in symptomatic ambulatory patients are located in the distal ( calf ) veins . While proximal disease warrants therapeutic anticoagulation to reduce the associated risks , distal DVT often goes untreated . However , a proportion of untreated distal disease will undoubtedly propagate or embolize . Concern also exists that untreated disease could lead to long-term post thrombotic changes . Currently , it is not possible to predict which distal thrombi will develop such complications . Whether these potential risks outweigh those associated with unrestricted anticoagulation remains unclear . The Anticoagulation of Calf Thrombosis ( ACT ) trial aims to compare therapeutic anticoagulation against conservative management for patients with acute symptomatic distal deep vein thrombosis . Methods ACT is a pragmatic , open-label , r and omized controlled trial . Adult patients diagnosed with acute distal DVT will be allocated to either therapeutic anticoagulation or conservative management . All patients will undergo 3 months of clinical and assessor blinded sonographic follow-up , followed by 2-year final review . The project will commence initially as an external pilot study , recruiting over a 16-month period at a single center to assess feasibility measures and clinical event rates . Primary outcome measures will assess feasibility endpoints . Secondary clinical outcomes will be collected to gather accurate data for the design of a definitive clinical trial and will include : ( 1 ) a composite endpoint combining thrombus propagation to the popliteal vein or above , development of symptomatic pulmonary embolism or sudden death attributable to venous thromboembolic disease ; ( 2 ) the incidence of major and minor bleeding episodes ; ( 3 ) the incidence of post-thrombotic leg syndrome at 2 years using a vali date d screening tool ; and ( 4 ) the incidence of venous thromboembolism ( VTE ) recurrence at 2 years . Discussion The ACT trial will explore the feasibility of comparing therapeutic anticoagulation to conservative management in acute distal DVT , within a modern cohort . We also aim to provide contemporary data on clot propagation , bleeding rates and long-term outcomes within both groups . These results will inform the conduct of a definitive study if feasibility is established . Trial registration Current Controlled Trials IS RCT Summary Background Deep vein thrombosis ( DVT ) and pulmonary embolism are common after stroke . In small trials of patients undergoing surgery , graduated compression stockings ( GCS ) reduce the risk of DVT . National stroke guidelines extrapolating from these trials recommend their use in patients with stroke despite insufficient evidence . We assessed the effectiveness of thigh-length GCS to reduce DVT after stroke . Methods In this outcome -blinded , r and omised controlled trial , 2518 patients who were admitted to hospital within 1 week of an acute stroke and who were immobile were enrolled from 64 centres in the UK , Italy , and Australia . Patients were allocated via a central r and omisation system to routine care plus thigh-length GCS ( n=1256 ) or to routine care plus avoidance of GCS ( n=1262 ) . A technician who was blinded to treatment allocation undertook compression Doppler ultrasound of both legs at about 7–10 days and , when practical , again at 25–30 days after enrolment . The primary outcome was the occurrence of symptomatic or asymptomatic DVT in the popliteal or femoral veins . Analyses were by intention to treat . This study is registered , number IS RCT N28163533 . Findings All patients were included in the analyses . The primary outcome occurred in 126 ( 10·0 % ) patients allocated to thigh-length GCS and in 133 ( 10·5 % ) allocated to avoid GCS , result ing in a non-significant absolute reduction in risk of 0·5 % ( 95 % CI −1·9 % to 2·9 % ) . Skin breaks , ulcers , blisters , and skin necrosis were significantly more common in patients allocated to GCS than in those allocated to avoid their use ( 64 [ 5 % ] vs 16 [ 1 % ] ; odds ratio 4·18 , 95 % CI 2·40–7·27 ) . Interpretation These data do not lend support to the use of thigh-length GCS in patients admitted to hospital with acute stroke . National guidelines for stroke might need to be revised on the basis of these results . Funding Medical Research Council ( UK ) , Chief Scientist Office of Scottish Government , Chest Heart and Stroke Scotl and , Tyco Healthcare ( Covidien ) USA , and UK Stroke Research Network Little is known about the efficacy of graduated compression stockings in preventing venous thromboembolism after hip surgery . We conducted a prospect i ve , r and omised single-blind study to determine whether the addition of compression stockings to fondaparinux conferred any additional benefit . The study included 874 patients , of whom 795 could be evaluated ( 400 in the fondaparinux group and 395 in the fondaparinux plus compression stocking group ) . Fondaparinux was given post-operatively for five to nine days , either alone or combined with wearing stockings , which were worn for a mean 42 days ( 35 to 49 ) . The study outcomes were venous thromboembolism , or sudden death before day 42 . Duplex ultrasonography was scheduled within a week of day 42 . Safety outcomes were bleeding and death from venous thromboembolism . The prevalence of deep-vein thrombosis was similar in the two groups 5.5 % ( 22 of 400 ) in the fondaparinux group and 4.8 ( 19 of 395 ) in the fondaparinux plus stocking group ( odds ratio 0.88 , 95 % confidence interval 0.46 to 1.65 , p = 0.69 ) . Major bleeding occurred in only one patient . The addition of graduated compression stockings to fondaparinux appears to offer no additional benefit over the use of fondaparinux alone The efficacy of graduated compression stockings in the prevention of deep vein thrombosis ( DVT ) after major gynaecological surgery was investigated in a controlled r and omized prospect i ve trial in 196 patients who were > 35 years of age . The stockings were worn by 104 of the 196 patients throughout their stay in hospital , the other 92 patients did not wear the stockings ( control group ) . All the patients were scanned for DVT postoperatively with the 125I‐labelled fibrinogen test . None of the 104 patients who wore the stockings developed a thromboembolism , but four of the 92 control patients who did not wear the stockings had DVT . This difference between the two groups was statistically significant The mechanisms by which graduated compression stockings prevent deep venous thrombosis are not completely understood . In the current study the physiologic effect of low-pressure graduated compression stockings on the venous blood flow in the lower limb and the practical aspects of their use were assessed . Patients having elective orthopaedic surgery at a university orthopaedic department were r and omized into five groups to wear two different types of graduated compression stockings in thigh and knee lengths . Patients in the fifth control group did not wear graduated compression stockings . Venous occlusion strain gauge plethysmography was used to measure venous flow . After 20-minutes bed rest there was a highly significant increase in venous capacitance and venous outflow in patients in all of the four groups wearing stockings . There was no difference in the mean of the percentage change of venous capacitance in patients in the four groups wearing stockings . The knee length Brevet stockings were less efficient in increasing the venous outflow . There was no significant change in the venous capacitance and venous outflow in patients in the control group . Visual assessment of the fit and use of stockings was done , and patients ’ subjective opinion of comfort was sought . The knee length graduated compression stockings wrinkled significantly less , and significantly fewer patients reported discomfort with them . All stockings were reported to be difficult to use . Thigh and knee length stockings have a significant effect on decreasing venous stasis of the lower limb . Knee length graduated compression stockings are similarly efficient in decreasing venous stasis , but they are more comfortable to wear , and they wrinkle less INTRODUCTION Pneumatic compression stocking ( PCS ) devices have been introduced to decrease the incidence of postoperative deep venous thrombosis ( DVT ) . However , their role in the prophylaxis against pulmonary embolism ( PE ) remains unclear . This study was undertaken to compare the prophylactic effectiveness of subcutaneous heparin ( SCH ) alone vs the combined use of PCS and SCH in the prevention of PE following cardiac surgery . METHODS We studied 2,551 consecutive patients who underwent cardiac surgery over a 10-year period . They were r and omly allocated to two groups . Group A included 1,196 patients who were treated with 5,000 U of SCH every 12 h and group B included 1,355 patients treated with a combined prophylactic regimen of PCS and SCH . RESULTS The diagnosis of PE was established in 69 patients by either high-probability ventilation perfusion scan , pulmonary angiogram , or autopsy . The incidence of PE in group A patients was 4 % ( 48/1,196 ) and in group B was 1.5 % ( 21/1,355 ) . The concomitant use of bilateral PCS and SCH reduced the frequency of postoperative PE in 62 % in comparison to the prophylaxis with SCH alone ( p < 0.001 ) . CONCLUSIONS These data suggest that the combined prophylactic method of bilateral PCS and SCH is superior to SCH alone in the prevention of PE after cardiac surgery A prospect i ve , r and omized study was conducted to assess the efficacy of pulsatile pneumatic plantar compression for prophylaxis against deep venous thrombosis after total knee arthroplasty performed with use of regional anesthesia . One hundred and twenty-two patients ( 164 knees ) who were scheduled to have a unilateral or a one-stage bilateral total knee arthroplasty were separately r and omized to be managed with either aspirin alone or the pulsatile pneumatic plantar-compression device and aspirin . The prevalence of deep venous thrombosis was 27 per cent ( twenty-two of eighty-one knees ) in the group treated with pneumatic plantar compression compared with 59 per cent ( forty-nine of eighty-three knees ) in the patients managed with aspirin alone ( the control group ) ( p < 0.001 ) . A significant difference was also noted in the group that had had a unilateral arthroplasty ( a prevalence of 27 per cent [ eleven of forty-one knees ] in the group treated with pneumatic plantar compression , compared with 67 per cent [ twenty-six of thirty-nine knees ] in that treated with aspirin alone ; p < 0.006 ) and in the group that had had a one-stage bilateral procedure ( a prevalence of 28 per cent [ eleven of forty knees ] in the group treated with pneumatic plantar compression , compared with 52 per cent [ twenty-three of forty-four knees ] in that treated with aspirin alone ; p < 0.03 ) . No proximal thrombi were noted in any patient who used the pulsatile pneumatic plantar-compression device , while the prevalence of proximal thrombosis in the popliteal or femoral veins was 14 per cent ( twelve of eighty-three knees ) in the group treated with aspirin alone ( p < 0.0003 ) . In the group treated with a unilateral procedure and aspirin alone the prevalence of proximal thrombosis was 13 per cent ( five of thirty-nine knees ; p < 0.02 ) , while in the group treated with a bilateral procedure and aspirin alone it was 16 per cent ( seven of forty-four knees ; p < 0.01 ) . Only in the patients who had had a unilateral procedure was use of the compression device associated with significantly less edema postoperatively than was use of aspirin alone . The change between the preoperative and postoperative circumferences of the thigh and leg was significantly less ( 9 ± 4.1 millimeters [ mean and st and ard deviation ] less for the thigh [ p < 0.01 ] and 6 ± 3.9 millimeters less for the leg [ p < 0.049 ] ) with the compression device than with aspirin alone . In addition , there was significantly less mean drainage ( 98 ± 61.1 milliliters ) in the group treated with a unilateral procedure and pneumatic compression , compared with that treated with a unilateral procedure and aspirin alone ( p < 0.041 ) . An internal timer of the compression device was used to assess the compliance of the patient with use of the device , and a relationship between deep venous thrombosis and the total duration of treatment with the device was found . The patients in whom deep venous thrombosis did not develop used the device for a mean of 96 ± 23.4 hours ( range , sixty to 164 hours ) postoperatively , or 19.2 ± 5.1 hours a day , while those in whom thrombosis developed used it for a mean of 67 ± 21.1 hours ( range , twenty-six to 101 hours ) , or 13.4 ± 4.3 hours a day ( p < 0.001 ) . No untoward effects were noted in any patient who used the device . This study confirms the safety and efficacy of pulsatile pneumatic plantar compression and aspirin compared with aspirin alone and supports the use of mechanical compression for prophylaxis against deep venous thrombosis and for reduction of edema in patients who have had a total knee arthroplasty . In addition , we found a direct relationship between compliance with the use of this device and its efficacy in reducing deep venous thrombosis The frequency of deep venous thrombosis ( DVT ) was studied in 98 patients undergoing major abdominal surgery . All the patients received low dose heparin prophylaxis 5000 i.u . every 12 h for 5–7 days . In each patient , a graduated compression stocking was also worn and r and omly allocated to one of the legs and the other leg served as a control . DVT was diagnosed by the 125I‐fibrinogen method . Four patients developed bilateral DVT and 8 patients unilateral DVT , all of whom developed it in the control leg . The difference in unilateral DVT between stockinged and control legs was significant ( P < 0·004 ) . It is concluded that a combination of low dose heparin and graduated compression stockings is more effective than low dose heparin alone in reducing the frequency of postoperative DVT . It is suggested that this combination of prophylaxis might be of value in high risk patients Background : Patients have been shown to be at greater risk for deep venous thrombosis , particularly proximal thrombosis , after total hip arthroplasty . Proximal thrombi are more likely to develop into pulmonary emboli than are distal thrombi . The purpose of this r and omized , prospect i ve study was to compare the prevalence of pelvic and proximal lower-extremity deep venous thrombosis after primary total hip arthroplasty between patients treated with an impulse mechanical compression device for prophylaxis and those treated with prophylactic stockings . Methods : One hundred patients were evaluated , with use of magnetic resonance venography , for proximal deep venous thrombosis after total hip arthroplasty . Fifty patients were treated with a mechanical compression device on both lower extremities , and the other fifty patients received only prophylactic stockings . Both groups of patients received hypotensive epidural anesthesia and 325 mg of aspirin twice a day . Results : Overall , proximal deep venous thrombi were found in 15 % of the 100 patients . Of the fifty patients treated with mechanical compression , 8 % ( four ) had a positive venogram . Of the fifty control patients , 22 % ( eleven ) had a positive venogram ( p < 0.05 ) . However , overall the rate of occlusive thrombi was 6 % ( six ) compared with an overall rate of nonocclusive thrombi of 9 % ( nine ) . The rate of occlusive thrombi was 2 % ( one of fifty ) in the study group and 10 % ( five of fifty ) in the control group ( p = 0.04 ) . Conclusions : On the basis of this study , we concluded that patients managed with total hip arthroplasty benefit from a reduction in the rates of femoral and pelvic deep vein thrombosis when they are treated with hypotensive epidural anesthesia , mechanical compression , and aspirin and are subsequently assessed with magnetic resonance venography OBJECTIVE The aim of this study was to compare the efficacy of low molecular weight heparin ( LMWH ) combined with graduated compression stockings ( GCS ) with GCS alone as prophylactic measures for venous thromboembolism ( VTE ) in post-operative patients with gynecologic cancer . METHODS Patients diagnosed with gynecologic cancer undergoing primary major surgery between 2010 and 2011 in our institute were r and omized to receive LMWH+GCS or GCS as VTE prophylaxis post-operatively . RESULTS Altogether 247 patients were enrolled . The incidence of VTE in patients treated with LMWH + GCS was significantly lower than that in patients using GCS alone ( 0.8 % Vs . 8.1 % , P = 0.01 ) . There were no severe bleeding complications in the patients with prophylactic use of LMWH and the occurrence rate of wound dehiscence was comparable between the two groups ( P > 0.05 ) . Multivariable logistic regression analysis revealed that age over 60 years ( P = 0.015 ) , duration of operation over 3 hours ( P = 0.04 ) and without prophylactic use of LMWH ( P = 0.02 ) were independent risk factors for VTE . CONCLUSIONS Dual prophylaxis with LMWH and GCS should be recommended for gynecologic cancer patients undergoing major surgery for its better efficacy than GCS . Prophylactic use of LMWH is safe and convenient . Patients with older age and prolonged operation time are at highest risk of developing VTE post-operatively The efficacy of graduated compression stockings in the prevention of postoperative deep vein thrombosis was studied in a r and omized , prospect i ve , controlled trial of 200 patients , aged 40 years and over , undergoing abdominal surgery ( 100 for benign disease , 100 for malignant conditions ) . Deep vein thrombosis was diagnosed by the 125I‐fibrinogen test . The incidence of deep vein thrombosis was 35·9 per cent in the control group ( 103 patients ) and 15·5 per cent in the stockinged group ( 97 patients ) ( P < 0·025 ) . In the patients with benign disease , deep vein thrombosis developed in 24·5 per cent of the control limbs and 6·1 per cent of stockinged limbs ( P < 0·005 ) ; in patients with malignant disease the similar figures were 27·9 and 11·5 per cent ( P < 0·05 ) . Increasing age did not alter the efficacy of the stockings . It is concluded that graduated compression stockings provide a safe and effective method of prophylaxis against deep vein thrombosis A prospect i ve , r and omized trial of the effect of grade d compression of the calf was done in 62 patients operated on electively for hip disease . After total hip arthroplasty , compression reduced the number of positive fibrinogen uptake tests by two-thirds , significant only in males , who seem to run a higher risk of thrombosis than females Perioperative anticoagulant prophylaxis for postoperative venous thromboembolism ( VTE ) in neurosurgical patients has not gained wide acceptance due to the fear of intracranial bleeding . Physical methods give a worthwhile reduction of postoperative VTE but there still remains a substantial residual incidence . In other clinical indications , low molecular weight heparins have proven to be effective for prophylaxis of VTE when administered postoperatively , with the advantage of no bleeding enhancement during surgery . Therefore , we performed a multicentre , r and omized , double-blind trial in neurosurgical patients to investigate the efficacy and safety of adding a low molecular weight heparin ( LMWH ) , nadroparin , initiated postoperatively , to graduated compression stockings in the prevention of VTE . Deep-vein thrombosis was detected by m and atory venography . Bleeding was determined according to pre-defined objective criteria for major and minor episodes . An adequate bilateral venogram was obtained in 166 of 241 LMWH patients ( 68.9 % ) and 179 of 244 control patients ( 73.4 % ) . A total of 31 of 166 LMWH patients ( 18.7 % ) and 47 of 179 controls patients ( 26.3 ) had VTE up to Day 10 postoperatively ( p = 0.047 ) . The relative risk reduction ( RRR ) was 28.9 % . The rates for proximal deep-vein thrombosis/pulmonary embolism were 6.9 % and 11.5 % for the two groups , respectively ( RRR : 40.2 % ; p = 0.065 ) . Secondary analyses involved all VTE up to day 56 post-surgery which was detected in 33 patients of 241 in the LMWH group ( 13.7 % ) and 51 of 244 control patients ( 20.9 % ; RRR 34.5 % ; p = 0.018 ) . The corresponding percentages for proximal deep-vein thrombosis/pulmonary embolism were 5.8 % and 10.2 % for the two groups , respectively , giving a RRR of 43.3 % ; p = 0.36 . Major bleeding complications , during the treatment period , occurred in six low molecular weight heparin treated patients ( 2.5 % ) and in two control patients ( 0.8 % ) ; p = 0.87 . A higher mortality was observed in the low molecular weight heparin group over the 56-day follow-up period ( 22 versus 10 ; p = 0.026 ) . However , none of these deaths was judged by a blinded adjudication committee to be related to the study drug . In conclusion , this study demonstrates that the low molecular weight heparin , nadroparin , added to graduated compression stockings results in a clinical ly significant decrease in VTE without inducing any significant increase of major bleeding A r and omized controlled study was undertaken to compare heparin with heparin plus graduated compression stockings ( Brevet Tx , Seton Healthcare ) in the prophylaxis of deep vein thrombosis ( DVT ) following abdominal surgery Objectives : Although patients with intracerebral hemorrhage ( ICH ) are at risk for deep venous thrombosis ( DVT ) , the data about preventive options for DVT prophylaxis in this population is insufficient . We investigated the safety of low dose low molecular weight heparin ( LMWH ) for DVT prophylaxis in patients with ICH and the effect of heparin on the enlargement of hemorrhage . Methods : We prospect ively r and omized 75 primary ICH patients to subcutaneous LMWH ( Enoxaparin sodium 40mg/d ) or long compression stockings ( CS ) after the first 48 hours . All patients had cranial computed tomography ( CT ) scan at admittance , 24th and 72nd hours , seventh and 21st days , CT pulmonary angiography and bilateral lower extremity venous Doppler at 7th day . Hematoma volumes were calculated on the initial and follow-up CTs with ABC/2 method . Results : Mean ± SD age of the patients was 68.1 ± 11.98 and 66.08 ± 9.55 in LMWH and CS groups , respectively . Twenty-two of LMVH group and 8 of CS group were female . After r and omization to LMWH or CS , we did not observe any hematoma enlargement at 72nd hours , 7 and 21st days in both groups . In addition , there was not any other systemic bleeding complication in LMWH group . We detected 4 asymptomatic DVT in our patients ( 3 in LMWH and 1 in CS group ) . Although asymptomatic DVT was more common in LMWH group , it was not statistically significant ( P = 1 ) . Conclusions : Low dose heparin treatment after 48 hours of stroke in ICH patients is not associated with an increased hematoma growth and should be used for DVT and PE prophylaxis BACKGROUND The reason some patients with deep venous thrombosis ( DVT ) develop the postthrombotic syndrome is not well understood . OBJECTIVE To determine the frequency , time course , and predictors of the postthrombotic syndrome after acute DVT . DESIGN Prospect i ve , multicenter cohort study . SETTING 8 Canadian hospital centers . PATIENTS 387 out patients and in patients who received an objective diagnosis of acute symptomatic DVT were recruited from 2001 to 2004 . MEASUREMENTS St and ardized assessment s for the postthrombotic syndrome using the Villalta scale at 1 , 4 , 8 , 12 , and 24 months after enrollment . Mean postthrombotic score and severity category at each interval was calculated . Predictors of postthrombotic score profiles over time since diagnosis of DVT were identified by using linear mixed modeling . RESULTS At all study intervals , about 30 % of patients had mild ( score , 5 to 9 ) , 10 % had moderate ( score , 10 to 14 ) , and 3 % had severe ( score > 14 or ulcer ) postthrombotic syndrome . Greater postthrombotic severity category at the 1-month visit strongly predicted higher mean postthrombotic scores throughout 24 months of follow-up ( 1.97 , 5.03 , and 7.00 increase in Villalta score for mild , moderate , and severe 1-month severity categories , respectively , vs. none ; P < 0.001 ) . Additional predictors of higher scores over time were venous thrombosis of the common femoral or iliac vein ( 2.23 increase in score vs. distal [ calf ] venous thrombosis ; P < 0.001 ) , higher body mass index ( 0.14 increase in score per kg/m(2 ) ; P < 0.001 ) , previous ipsilateral venous thrombosis ( 1.78 increase in score ; P = 0.001 ) , older age ( 0.30 increase in score per 10-year age increase ; P = 0.011 ) , and female sex ( 0.79 increase in score ; P = 0.020 ) . LIMITATIONS Decisions to prescribe compression stockings were left to treating physicians rather than by protocol . Because international normalized ratio data were unavailable , the relationship between anticoagulation quality and Villalta scores could not be assessed . CONCLUSION The postthrombotic syndrome occurs frequently after DVT . Patients with extensive DVT and those with more severe postthrombotic manifestations 1 month after DVT have poorer long-term outcomes Two hundred and forty-five patients who underwent acute extensive abdominal operations were r and omized into three regimens to achieve optimal prophylaxis of postoperative thromboembolic complications . All of the patients were screened by the 125I-fibrinogen uptake test for seven days and if the phlebographic findings were positive . Of 81 patients receiving low dose heparin , 12 had thromboembolism . Of 79 receiving a combination of low dose heparin and grade d compression stockings , two had thromboembolism , and of 85 receiving a combination of dextran and grade d compression stockings , 13 had this complication . This difference is significant in favor of the second treatment ( p = 0.013 ) . It is concluded that the combination of low dose heparin and grade d compression stockings is an effective way to prevent thromboembolism after acute abdominal operations Above‐knee graduated compression stockings are effective in preventing postoperative deep vein thrombosis , but are more expensive and less acceptable than below‐knee stockings . One hundred and fourteen patients undergoing major abdominal surgery were r and omly allocated to wear above‐knee or below‐knee graduated compression stockings . Deep vein thromboses were diagnosed by isotope uptake in three of 56 patients ( 5·4 per cent ) in the above‐knee group and one of 58 patients ( 1·7 per cent ) in the below‐knee group . These differences are not statistically significant . Results suggest that below‐knee stockings are as effective as above‐knee in the prevention of postoperative deep vein thrombosis In a double-blind prospect i ve clinical trial 75 consecutive patients undergoing mastectomy were r and omly allocated to one of three groups . Twenty-five patients received perioperative anti-thromboembolic therapy with sodium heparin and 25 with calcium heparin . The remaining 25 patients were given anti-embolism stockings but no heparin . The total postoperative blood loss and period of drainage did not differ between the two groups given heparin , but a total of 10 of these 50 patients suffered haemorrhagic complications in the form of severe bruising or haematoma postoperatively . Of the patients given no heparin , none suffered haemorrhagic complications and the blood loss following the first 24-hour postoperative period was significantly less than in the groups given heparin OBJECTIVE To compare the effects of elastic b and age compression with the specific hemostasis devices in patients undergoing transradial coronary intervention . METHODS A total of 3000 consecutive patients were r and omized to 3 groups and 2910 patients completed the study , 963 patients in elastic b and age group ( ER ) , 976 in T b and group ( TB ) and 971 in balloon group ( TR ) . In-hospital vascular related complication was the primary study endpoint . The secondary endpoints included : risk factors of complications , compression time , fibroplasia conditions and the comfort feeling of patients . RESULTS The overall incidence of vascular related complication in 3 groups was similar ( P = 0.262 ) . Female , low body weight , prolongation of procedure and multi-punctures were identified as the independent risk factors for complications . Moreover , the compression time and the fibroplasia condition in TB and TR group were superior to those in the ER group . Comfortable feeling of the patients was better in TR and TB group than in ER group ( P < 0.001 ) . CONCLUSIONS Both conventional b and age device and specific radial device are feasible and associated with low incidence of vascular complication . However , the specific radial device has significant advantage over b and age strategy in compression time and quality of life OBJECTIVE To evaluate the efficacy of intermittent pneumatic compression ( IPC ) in the prevention of venous thromboembolism ( VTE ) in medical critically ill patients . METHODS A prospect i ve , r and omized , controlled study was conducted . One hundred and sixty-two medical critically ill patients were r and omly assigned to IPC group and control group by r and om number table after admitted to intensive care unit ( ICU ) from June 2008 to June 2010 . Patients under anticoagulation medicine therapy were excluded . Patients in the IPC group were treated with IPC to prevent VTE after ICU admission . No measures were taken to prevent VTE in the control group . The rate of VTE [ deep vein thrombosis ( DVT ) and pulmonary embolism ( PE ) ] , duration of mechanical ventilation(MV ) , the length of stay in ICU , rate of non-sudden cardiac death and ICU mortality rate and related side-effects of IPC were compared during the subsequent 28 days between two groups . RESULTS Compared with control group , IPC group was shown to have a significantly lower rate of DVT [ 3.80%(3/79 ) vs. 19.28%(16/83 ) , P<0.01 ] , lower rate of PE [ 0 ( 0/79 ) vs. 9.64%(8/83 ) , P<0.01 ] and lower rate of non-sudden cardiac death [ 1.26%(1/79 ) vs. 7.23%(6/83 ) , P<0.01 ] . Compared with control group , duration of MV ( days : 8±6 vs. 9±8 ) and length of stay in ICU ( days : 9±7 vs. 10±7 ) were shorter , and the ICU mortality rate of 28 days ( 24.05 % vs. 31.32 % ) was lower in the IPC group , but they were not statistically significant ( all P>0.05 ) . No related side-effects were found in the IPC group . CONCLUSION IPC can prevent VTE , and lower the rate of non-sudden cardiac death , and it is safe in medical critically ill patients different pneumatic compression devices , we found that cigarette smokers had a lower incidence of isotopic thrombosis than nonsmokers , but the reason for this is unknown . Isotopically apparent leg vein thromboses may cause no symptoms or at worst an illness which , though adding to the patient 's burden , is not in itself lethal . Pulmonary emboli , on the other h and , may be immediately lethal or at least cause severe illness . Patients without isotopic evidence of leg vein thrombosis do not get pulmonary emboli . On the other h and , though some prophylactic methods ( notably dextran ) may not greatly reduce the incidence of leg vein thrombi , they do protect against pulmonary embolism . The fibrinogen uptake test has , therefore , its limitations . What is needed now is a change in the way of assessing the efficacy of prophylaxis . Trials which judge the ability of a method to prevent lethal pulmonary emboli can be carried out only in centres with high necropsy rates , with large numbers of patients , and with the cooperation of pathologists with a particular interest in the subject . Morrell and Dunnill studied the lungs in 246 necropsies of medical and surgical patients over the age of 40 years . They found 31 ( 13 % ) major emboli in the left lungs ( which were examined by routine slicing ) but no less Symposium on Deep venous thrombosis and pulmonary emboli are reported to occur in up to 66 % of the patients undergoing a major urological operation . Thromboembolic stockings , external sequential pneumatic compression stockings and anticoagulant agents , such as heparin sodium plus dihydroergotamine mesylate , have been suggested to decrease the risk of deep venous thrombosis and pulmonary emboli . A total of 74 evaluable patients undergoing a major urological operation was r and omized to receive either thromboembolic stockings , external sequential pneumatic compression stockings , or heparin plus dihydroergotamine as prophylaxis against deep venous thrombosis and pulmonary emboli . 111Indium-labeled platelet scans , performed preoperatively and on days 1 , 3 and 6 postoperatively , were used to diagnose deep venous thrombosis and pulmonary emboli . Mean patient age was 63 years and all but 1 operation was performed for neoplastic disease . Deep venous thrombosis was detected in 5 of 25 patients ( 20 % ) with thromboembolic stockings , 3 of 24 ( 12.5 % ) with external sequential pneumatic compression stockings and 2 of 25 ( 8 % ) with heparin plus dihydroergotamine . There was no difference in blood loss or complications among the groups . Although statistical significance among the treatment groups was not reached in this study , the trend to a decrease in deep venous thrombosis and pulmonary emboli with external sequential pneumatic compression stockings and heparin plus dihydroergotamine , and an absence of an increase in morbidity in these groups supports the use of these modalities to decrease the morbidity and mortality of deep venous thrombosis and pulmonary emboli After an episode of deep venous thrombosis ( DVT ) 224 patients were ran domized into four groups : a control group ( A ; 63 subjects ) ; one receiving pro phylaxis with indobufen ( B ; 60 patients ) —an oral antiplatelet agent ; one using graduated elastic compression stockings ( C ; 53 ) ; and one receiving prophylaxis with both indobufen and graduated stockings ( D ; 48 ) . Patients were monitored over a three-year period with color duplex scanning repeated every three months . In 46 % of the controls there was at least one episode of recurrent DVT ( RDVT ) . In patients receiving indobufen ( group B ) and using graduated com pression stockings ( group C ) the incidence of RDVT was significantly lower ( 5 % and 9.43 % , respectively ) . The incidence of RDVT was further significantly re duced by the combination of the two methods ( group D ) ( 2.08 % ) . In conclusion , RDVT is common and often asymptomatic and can be effec tively prevented by prophylaxis with indobufen or graduated compression and more effectively by the combination of the two methods BACKGROUND Knee arthroscopy , the most common orthopedic operation worldwide , carries a definite risk for deep venous thrombosis ; however , postsurgical thromboprophylaxis is not routinely recommended . OBJECTIVE To evaluate whether low-molecular-weight heparin ( LMWH ) better prevents deep venous thrombosis and does not cause more complications than graduated compression stockings in adults having knee arthroscopy . DESIGN Assessor-blind , r and omized , controlled trial . SETTING The Department of Knee Surgery , Abano Terme Clinic , Abano Terme ( knee surgery , r and om assignment , and bleeding event survey ) , and the Unit of Angiology , University Hospital of Padua , Padua ( efficacy outcomes evaluation , follow-up , data management , and analysis ) , Italy . PATIENTS 1761 consecutive patients undergoing knee arthroscopy between March 2002 and January 2006 . INTERVENTION Patients were r and omly assigned to wear full-length graduated compression stocking for 7 days ( 660 patients ) or to receive a once-daily subcutaneous injection of LMWH ( nadroparin , 3800 anti-Xa IU ) for 7 days ( 657 patients ) or 14 days ( 444 patients ) . The data and safety monitoring board prematurely stopped the 14-day heparin group after the second interim analysis . MEASUREMENTS Combined incidence of asymptomatic proximal deep venous thrombosis , symptomatic venous thromboembolism , and all-cause mortality ( primary efficacy end point ) and combined incidence of major and clinical ly relevant bleeding events ( primary safety end point ) . All patients had bilateral whole-leg ultrasonography at the end of the allocated prophylactic regimen or earlier if indicated . All patients with normal findings were followed for 3 months , and none was lost to follow-up . RESULTS The 3-month cumulative incidence of asymptomatic proximal deep venous thrombosis , symptomatic venous thromboembolism , and all-cause mortality was 3.2 % ( 21 of 660 patients ) in the stockings group , 0.9 % ( 6 of 657 patients ) in the 7-day LMWH group ( absolute difference , 2.3 percentage points [ 95 % CI , 0.7 to 4.0 percentage points ] ; P = 0.005 ) , and 0.9 % ( 4 of 444 patients ) in the prematurely stopped 14-day LMWH group . The cumulative incidence of major or clinical ly relevant bleeding events was 0.3 % ( 2 of 660 patients ) in the stockings group , 0.9 % ( 6 of 657 patients ) in the 7-day LMWH group ( absolute difference , -0.6 percentage point [ CI , -1.5 to 0.2 percentage points ] ) , and 0.5 % ( 2 of 444 patients ) in the 14-day LMWH group . LIMITATIONS The study was not double-blind or double-dummy . Almost half of the events making up the composite outcome measure were distal deep venous thromboses . Stockings were used instead of placebo because of local prophylaxis policies . CONCLUSION In patients undergoing knee arthroscopy , prophylactic LMWH for 1 week reduced a composite end point of asymptomatic proximal deep venous thrombosis , symptomatic venous thromboembolism , and all-cause mortality more than did graduated compression stockings In an open controlled study , 248 consecutive patients ( age more than 40 yrs ) admitted for major abdominal surgery were r and omized to one of three prophylactic antithrombotic treatments . Eighty-five patients received subcutaneous heparin , 74 patients had graduated compression stockings to the knee ( TED stockings ) , and 89 patients had both subcutaneous heparin and stockings . Treatment began on the evening before operation and continued to complete mobilization , or for not less than five days postoperatively . On the fourth or fifth postoperative day , the patients underwent a 99mTc-plasmin test of the lower limbs as a test for deep vein thrombosis . There were 29.7 % positive tests in the stocking group , 29.4 % in the group with heparin prophylaxis , and 25.8 % in the combined group . Differences between treatments were not statistically significant BACKGROUND Deep vein thrombosis ( DVT ) is an important complication of stroke , but the evidence to support commonly used prophylactic strategies is conflicting . OBJECTIVES To describe the incidence , extent , associated clinical features and evolution of DVT after stroke . PATIENTS / METHODS The CLOTS trials 1 and 2 together r and omized 5632 immobile stroke patients in 135 hospitals in nine countries . We screened patients for asymptomatic DVT with compression duplex ultrasound ( CDU ) at about 7 - 10 days and again at about 25 - 30 days after enrollment . RESULTS Six hundred and forty-one ( 11.4 % ) of 5632 patients had DVT detected on the first CDU scan at a median of 8 days ( interquartile range [ IQR ] 7 - 10 days ) after enrollment , and an additional 176 ( 3.1 % ) had a DVT on the second CDU scan at a median of 28 days ( IQR 26 - 30 days ) . Of the 817 with DVTs , 289 ( 35 % ) were symptomatic and 39 ( 5 % ) had pulmonary embolism ( PE ) confirmed by imaging . Six hundred and seventy-six ( 83 % ) were unilateral , 141 ( 17 % ) were bilateral , 322 ( 39 % ) were limited to calf veins , 172 ( 21 % ) were popliteal , and 323 ( 40 % ) were femoral . Among the 542 patients with DVT and a weak leg , the DVT affected the weaker leg in 396 ( 73 % ) , the stronger leg in 59 ( 11 % ) , and was bilateral in 87 ( 16 % ) . Among the 318 patients with a DVT detected on the first CDU scan who had a second scan , the DVT regressed in 148 ( 47 % ) , stayed the same in 140 ( 44 % ) , and progressed in only 30 ( 9 % ) . CONCLUSIONS Although most DVTs develop within the first week , some develop later , and some early DVTs progress . Any prophylaxis needs to be started early but ideally continued for at least 4 weeks Two hundred and eighty-six patients were divided into two groups according to the presence or absence of major risk factors . The so-called " at risk " patients were treated with continuous post-operative heparin therapy combined or not with anti-thrombosis stockings . The patients regarded as not at risk were divided into 3 subgroups allocated at r and om to different treatments based on subcutaneous heparin in effective or sub-anticoagulant doses with and without stocking . All patients underwent phlebography before and 7 days after the operation . The incidence of post-operative thrombosis was significantly lower in the 137 patients treated with heparin and stocking ( 10.22 per cent ) than in the 131 patients treated with heparin alone ( 19.85 per cent ) UNLABELLED The study was aim ed at assessing efficacy and safety of using graduated compression b and age with the level of pressure in the area of the middle ankle amounting to 20 - 40 mm Hg as compared to the conventional profile ( 10 - 20 mm Hg in the ankle area ) in the composition of comprehensive prevention of postoperative venous thromboembolic complications ( VTEC ) in patients of a high-risk group . For this purpose we carried out a prospect i ve r and omized clinical study including a total of 100 surgical patients ( general surgery , neurosurgery ) from a group of high risk for the development of VTEC with the presence of 3 and more conditions predisposing to venous thrombosis . All patients were subdivided into two subgroups 50 patients each . Patients in both groups received anticoagulants in st and ard preventive doses from the first day after surgery or in the remote period . The Study group patients were treated by applying on the ankle a b and age of medium distensibility with the target pressure in the ankle area of 20 - 40 mm Hg measured by means of a portable manometer . The control group patients were treated by a similar b and age applied onto the ankle and femur with a pressure of 10 - 20 mm Hg . In all cases a special lining material was placed under the b and age . With the purpose of active screening of postoperative VTECs , prior to the beginning of the study and then each 3 - 5 days we performed ultrasound angioscanning and in case thrombosis was revealed we performed static perfusion scintigraphy of the lungs and /or echocardiography for verification of pulmonary embolism . The patients who died were subjected to post-mortem examination . We also assessed the frequency of correcting the b and age on the femur and crus . RESULTS The incidence rate of postoperative venous thrombosis in the Study Group amounted to 16.0 % ( 95 % CI : 5.8 - 26.2 % ) and in the Control Group 36.0 % ( 95 % CI : 22.7 - 49.3 % , p=0.039 ) , with no significant differences in the incidence of proximal thrombosis or pulmonary embolism revealed . Maximal reduction of the development of venous thrombosis was revealed in patients with lower-limb paralysis amounting to 69.5 % . The frequency of the development of cutaneous lesions under the b and age did not differ significantly between the subgroups , being 8 % and 12 % , respectively . The total number of corrections of the compression in the Control Group was significantly higher , amounting to 0.64±0.23 time a day versus 0.32±0.05 t/d ( p<0.0001 ) . CONCLUSION The use of an elevated compression profile makes it possible to decrease the incidence of postoperative VTECs , especially in patients with palsy , not increasing the rate of cutaneous lesions under the b and ages . Femoral compression provides no additional reduction of the incidence of thrombosis but creates an additional necessity of correcting the b and ages In a prospect i ve , controlled clinical study prevention of postoperative deep venous thrombosis by low-dose heparin ( Heparin Leo 5 000 I.U. subcutaneously twice daily ) was compared with grade d compression stockings ( TED stockings , Kendall Co. ) . One hundred and twelve patients , admitted during a period of one year for elective major surgery , were allocated to one of the two treatment groups . In order to detect deep venous thrombosis the 99mTc-plasmin test was performed before the operative procedure and again 5 days later . Ninety-seven patients completed the study ( 45 patients in the heparin group and 52 patients in the stocking group ) . Venous thromboembolism was detected in 4 patients ( 8.9 % ) in the heparin group and in 3 patients ( 5.8 % ) in the stocking group ( p greater than 0.05 ) . In 6 patients the plasmin test was positive and one patient in the heparin group died following pulmonary embolism . It is concluded that grade d compression stockings can be used as an alternative to low-dose heparin for prophylaxis against deep venous thrombosis in elective general surgery Venous volume ( venous capacity ) of the calf is low in patients with acute myocardial infa rct ion , who also have a high risk of deep vein thrombosis ( DVT ) . The effect of graduated compression stockings on the venous volume and on the incidence of DVT was therefore studied in 80 patients aged 70 years and above with acute myocardial infa rct ion . Graduated compression stockings were r and omly fitted to one leg , the other serving as a control , after which the venous volume was measured by strain gauge plethysmography . The incidence of DVT was measured by the 125I fibrinogen uptake test . Venous volume was significantly higher in legs treated with graduated compression stockings compared to control legs . DVT developed in eight control legs but not in any leg treated with graduated compression stockings ( P = 0.003 ) . DVT was also significantly more frequent in women compared to men and the majority of DVT developed in legs with very low venous volume values Objective To examine the duration and magnitude of increased risk of venous thromboembolism after different types of surgery . Design Prospect i ve cohort study ( Million Women Study ) . Setting Question naire data from the Million Women Study linked with hospital admission and death records . Participants 947 454 middle aged women in the United Kingdom recruited in 1996 - 2001 and followed by record linkage to routinely collected NHS data on hospital admissions and deaths . During follow-up 239 614 admissions were for surgery ; 5419 women were admitted , and a further 270 died , from venous thromboembolism . Main outcome measures Adjusted relative risks and st and ardised incidence rates for hospital admission or death from venous thromboembolism ( pulmonary embolism or deep vein thrombosis ) , by time since and type of surgery . Results Compared with not having surgery , women were 70 times more likely to be admitted with venous thromboembolism in the first six weeks after an inpatient operation ( relative risk 69.1 , 95 % confidence interval 63.1 to 75.6 ) and 10 times more likely after a day case operation ( 9.6 , 8.0 to 11.5 ) . The risks were lower but still substantially increased 7 - 12 weeks after surgery ( 19.6 , 16.6 to 23.1 and 5.5 , 4.3 to 7.0 , respectively ) . This pattern of risk was similar for pulmonary embolism ( n=2487 ) and deep venous thrombosis ( n=3529 ) . The postoperative risks of venous thromboembolism varied considerably by surgery type , with highest relative risks after inpatient surgery for hip or knee replacement and for cancer—1 - 6 weeks after surgery the relative risks were , respectively , 220.6 ( 187.8 to 259.2 ) and 91.6 ( 73.9 to 113.4 ) . Conclusion The risk of deep vein thrombosis and pulmonary embolism after surgery is substantially increased in the first 12 postoperative weeks , and varies considerably by type of surgery . An estimated 1 in 140 middle aged women undergoing inpatient surgery in the UK will be admitted with venous thromboembolism during the 12 weeks after surgery ( 1 in 45 after hip or knee replacement and 1 in 85 after surgery for cancer ) , compared with 1 in 815 after day case surgery and only 1 in 6200 women during a 12 week period without surgery Purpose . To compare the efficacy and safety of different modes of thromboembolic prophylaxis for elective total knee arthroplasty ( TKA ) in Asian patients . Methods . 440 low-risk patients undergoing TKA were r and omised into 4 equal groups : ( 1 ) no prophylaxis ( control ) , ( 2 ) graduated compression stockings ( GCS ) , ( 3 ) intermittent pneumatic compression ( IPC ) , and ( 4 ) low-molecular-weight heparin ( enoxaparin ) . Duplex ultrasonography was used as an assessment tool . Results . The deep vein thrombosis point prevalence was highest in the control group ( 22 % ) , which was significantly higher than in patients receiving IPC ( 8 % , p=0.032 ) or enoxaparin ( 6 % , p=0.001 ) . One patient each in the control and GCS groups developed a non-fatal pulmonary embolism . Patients on enoxaparin received more blood transfusions and 2 of them had major bleeding complications . Conclusion . IPC is the preferred method of thromboprophylaxis for TKA in Asian patients Abstract The 125 I-labelled-fibrinogen test permits the Summary incidence and progression of postoperative deep-vein thrombosis to be accurately assessed . The incidence of deep-vein thrombosis was 35 % in a group of sixty-five patients having conventional prophylactic measures . More intensive measures , design ed to protect the legs from pressure and to promote venous flow during and after operation , were used in sixty-seven patients . The incidence of deep-vein thrombosis in this group ( 25 % ) was not significantly reduced , except in major operations in the elderly In a r and omized trial of neurosurgical patients , groups wearing graduated compression stockings alone ( group 1 ) or graduated compression stockings plus intermittent pneumatic compression ( IPC ) ( group 2 ) were compared with an untreated control group in the prevention of deep vein thrombosis ( DVT ) . In both active treatment groups , the graduated compression stockings were continued for 14 days or until hospital discharge , if earlier . In group 2 , IPC was continued for seven days . All patients underwent DVT surveillance with iodine 125-labeled fibrinogen leg scanning and impedance plethysmography . Venography was carried out if either test became abnormal . Deep vein thrombosis occurred in seven ( 8.8 % ) of 80 patients in group 1 , in seven ( 9.0 % ) of 78 patients in group 2 , and in 16 ( 19.8 % ) of 81 patients in the control group . The observed differences among these rates are statistically significant . The results of this study indicate that graduated compression stockings alone or in combination with IPC are effective methods of preventing DVT in neurosurgical patients Grade d compression stockings are commonly used to prevent deep-vein thrombosis ( DVT ) after stroke , but their efficacy in this setting has not been evaluated . Extrapolation of effectiveness from trials in patients undergoing elective surgery may be inappropriate . We undertook a r and omized , controlled trial , with blinded data review , in a University hospital Acute Stroke Unit . Patients were allocated to grade d compression stockings or to st and ard care alone . DVT incidence was determined at baseline and at day 7+/-2 by colour-flow Doppler ultrasound . Ninety-eight patients with acute , immobilizing stroke were r and omized ; 97 had full outcome data . One patient had clinical ly manifest DVT , and no patient had pulmonary thromboembolism . DVT was detected in 7/65 patients allocated stockings , and 7/32 controls ( odds ratio 0.43 , 95 % CI 0.14 - 1.36 ) ; DVT involving femoral veins was detected in 3/65 and 2/32 . In the first week after stroke , radiologically-detected DVT remains common , but is usually clinical ly silent . Proximal DVT is less common . Grade d compression stockings produced a reduction in DVT incidence comparable to that in other patient groups , but the reduction was not statistically significant , and the magnitude of effect size requires confirmation . There is greater doubt over efficacy in early prevention of proximal DVT The physiological effects of static compression of the leg have recently been reinvestigated . Grade d compression extending from the ankle to the upper thigh produces the maximum increase in velocity of femoral vein blood flow and the maximum decrease in clearance times of contrast media and radioisotopes from the deep veins of the calf . This type of compression may be easily produced by a specially design ed elastic stocking . Grade d compression was used in a controlled clinical trial of 98 patients undergoing major operations to assess its effect on isotopically diagnosed deep vein thrombosis . The incidence of deep vein thrombosis was 49 % in the control group and 23 % in the treated groups . No complications were caused by the stockings . Carefully design ed and correctly applied static compression is a safe and effective method of reducing the incidence of deep vein thrombosis Venous stasis of the legs during laparoscopic cholecystectomy was compared between patients without grade d compression leg b and ages ( Group 1 ; n = 12 ) and patients with such b and ages ( Group 2 ; n = 12 ) by measuring mean blood flow velocity and cross-sectional area of the femoral vein using a color Doppler ultrasonography . In Group 1 , when velocity and area were measured in the supine position , a significant decrease in velocity ( p < .05 ) and a significant increase in area ( p < .05 ) occurred after abdominal insufflation to 10 mm Hg . These changes were greater during abdominal insufflation in the reverse Trendelenburg position than during abdominal insufflation in the supine position . In Group 2 , flow velocity was significantly higher ( p < .05 ) before abdominal insufflation as compared with Group 1 . After abdominal insufflation to 10 mm Hg and a postural change , velocity significantly decreased ( p < .05 ) and area significantly increased ( p < .05 ) in Group 2 , similar to the results in Group 1 . During abdominal insufflation at 5 mm Hg or lower , the use of the grade d compression b and age was found to be useful for preventing femoral vein stasis . During abdominal insufflation at 10 mm Hg or in the reverse Trendelenburg position , the b and age did not prevent femoral vein stasis After total hip ( THR ) or knee replacement ( TKR ) , there is still an appreciable risk of developing deep-vein thrombosis despite prophylaxis with low-molecular-weight heparin ( LMWH ) . In a prospect i ve , r and omised study we examined the efficacy of LMWH in combination with intermittent pneumatic compression in patients undergoing primary unilateral THR or TKR . We administered 40 mg of enoxaparin daily to 131 patients combined with either the use of intermittent pneumatic compression or the wearing of graduated compression stockings . Compression ultrasonography showed no evidence of thrombosis after LMWH and intermittent pneumatic compression . In the group with LMWH and compression stockings the prevalence of thrombosis was 28.6 % ( 40 % after TKR , 14 % after THR ) . This difference was significant ( p < 0.0001 ) . In the early post-operative phase after THR and TKR , combined prophylaxis with LMWH and intermittent pneumatic compression is more effective than LMWH used with graduated compression stockings AIMS AND OBJECTIVES To compare the comfort levels of patients regarding the use of three different graduated compression stockings and to analyse the efficacies of the graduated compression stockings in relation to patient comfort and compliance in prevention of postoperative deep vein thrombosis . BACKGROUND Graduated compression stockings are very important with other prophylaxis methods in postoperative deep vein thrombosis prophylaxis . In meta-analyses and systematic review studies , it was reported that knee-length and thigh-length graduated compression stockings had similar efficacies . However , there is no r and omised study in literature regarding the patient problems and levels of comfort with the use of graduated compression stockings of different sizes and pressures . DESIGN A r and omised clinical trial design . METHODS A total of 219 patients were r and omised into three groups ( n = 73 in each group ) . Group I was given low-pressure , knee-length graduated compression stockings , group II was given low-pressure , thigh-length graduated compression stockings and group III was given moderate-pressure , knee-length graduated compression stockings . The level of patients comfort regarding the graduated compression stockings and occurrence of deep vein thrombosis were examined . RESULTS The vast majority of the patients ( 79·5 % ) in group III and 52·1 % of the patients in group II stated experiencing problems during the use of the graduated compression stockings ( p < 0·001 ) . The graduated compression stockings were reported by the patients as being very comfortable in the group I ( p < 0·001 ) . No findings of thrombosis were observed in any of the groups . CONCLUSION The low-pressure , knee-length graduated compression stockings are as effective as the other graduated compression stockings of different pressures and sizes in the postoperative deep vein thrombosis prophylaxis , and the patients have fewer problems while using these graduated compression stockings with a high satisfaction . RELEVANCE TO CLINICAL PRACTICE The combined use of pharmacological , mechanical and physical methods and patient education is effective in the prevention of postoperative deep vein thrombosis . The use of low-pressure , knee-length graduated compression stockings in clinical practice may be recommended , as the patients have fewer problems while using these graduated compression stockings with a high satisfaction One hundred and seventy‐six patients scheduled for elective major abdominal surgery were r and omized to two prophylactic regimens to prevent postoperative thromboembolism . All patients were screened with the 125I‐labelled fibrinogen uptake test , and thromboembolism was verified by ascending phlebography and /or perfusion/ventilation lung scintigraphy . In the group of patients receiving low‐dose heparin treatment ( 5000 units twice daily subcutaneously ) 12 per cent developed thromboembolic complications . In the other group , where low‐dose heparin treatment was supplemented with grade d compression stockings only 2 per cent developed thromboembolism . It is concluded that the combination of low‐dose heparin and the use of grade d compression stockings is superior to heparin alone in preventing thromboembolism following major abdominal surgery The effect of elastic compression on venous flow in the legs provided by carefully fitted stockings has been measured by a venographic technic . The stocking used provides a gradually decreasing compression from ankle to groin . Clearance of stagnant blood from behind venous valves is clearly improved and the differences observed are statistically highly significant . These data suggest that the routine use of carefully fitted compression stockings will result in a decreased incidence of deep vein thrombosis ( DVT ) and provide a singularly safe , convenient , and noninvasive method of prophylaxis . Evidence presented suggests that at least two investigators have failed to show a decreased incidence of DVT in limbs subjected to elastic compression because the method of compression was inadequate Grade d pressure stockings significantly reduced the incidence of venographically determined deep venous thrombosis ( DVT ) after total hip arthroplasty . Seventysix patients were studied ; the incidence of DVT was 54 per cent in 41 control patients and 20 per cent in 35 patients who wore stockings . Administration of blood during the operation and in the first 24 h after operation , if given in excess of blood loss , was associated with a significantly increased risk of developing DVT . The application of grade d pressure stockings and the avoidance of unnecessary perioperative blood transfusion are worth while in the management of total hip arthroplasty Mechanical prophylaxis with foot pumps provides an interesting alternative to chemical agents in the prevention of thromboembolic disease following major orthopaedic surgical procedures . Recent studies have suggested that the simultaneous use of graduated compression stockings ( GCS ) may hinder the pneumatic compression effect of foot pumps . The hypothesis of this prospect i ve study was that the use of foot pumps without GCS does not affect the efficacy of deep-vein thrombosis ( DVT ) prophylaxis and improves patient compliance . A total of 846 consecutive patients admitted at a single institution undergoing total hip ( THR ) or knee replacement ( TKR ) were included in the study . The A-V Impulse System foot-pump unit ( Orthofix Vascular Novamedix , And over , UK ) was used in all patients . Of these 846 patients , 46 discontinued the use of foot pumps , leaving 400 patients who received foot pumps in combination with GCS and 400 patients with foot pumps alone . Eleven patients of the stocking group ( 2.7 % ) and nine patients of the no-stocking group ( 2.3 % ) developed postoperative symptomatic DVT ( p = 0.07 ) . DVT was more frequent in TKR ( 10/364 ; 2.7 % ) than in THR ( 10/436 ; 2.3 % ) . Non-fatal pulmonary embolism occurred in four of the 20 patients with symptomatic DVT , two patients each of the stocking and no-stocking groups . The foot-pump discontinuation rate of patients treated with stockings was 7 % versus 4 % of the patients treated without stockings ( p < 0.05 ) . In conclusion , management of patients with foot pumps without GCS does not reduce the efficacy of DVT prophylaxis after THR and TKR and improves patient compliance . RésuméLa prophylaxie des complications thrombo-emboliques par « pompage » pédieux est une alternative au traitement médical en chirurgie orthopédique . Une étude récente a montré que l’utilisation simultanée de bas à compression élastique et de compression pneumatique au niveau du pied peut cacher l’effet de cette dernière technique . L’hypothèse émise pour ce travail prospect if est la suivante , l’utilisation de pompes au niveau des pieds sans bas de contention élastique n’entraîne pas de complications thrombo-emboliques complémentaires . 846 patients ayant bénéficié d’une prothèse totale de hanche et du genou ont été inclus dans cette étude . Le système utilisé a été le AV impluse système foot pump units de Orthofix Vascular Novamedix , And over . 46 patients ont bénéficié de la pompe en discontinue , 400 patients ont utilisé la pompe en combinaison avec les bas de contention et 400 patients la pompe uniquement.11 patients du groupe contention élastique ( 2,7 % ) et 9 patients du groupe sans contention ( 2,3 % ) ont présenté en post-opératoire une complication thrombo embolique ( p = 0.07 ) . Les complications de type thrombose veineuse profonde sont plus fréquentes dans la prothèse du genou ( 10 sur 364 ; 2.7 % ) que dans la prothèse de hanche ( 10 sur 436 ; 2,3 % ) . 4 embolies pulmonaires n’ayant entraîné aucun décès sont survenues sur un groupe de 20 patients ayant présenté une thrombose veineuse symptomatique , 2 dans le groupe bas de contention et deux dans le groupe sans bas de contention . Le système de pompe , au niveau du pied en discontinue associé à des bas de contention élastiques a été de 7 % en comparaison de patients traités sans contention 4 % ( p < 0.05 ) . En conclusion , l’utilisation d’un système de pompe au niveau du pied sans bas de contention élastique ne réduit pas l’efficacité de la prophylaxie du traitement des complications thrombo-emboliques de la prothèse totale de hanche dans la prothèse totale du genou et améliore le confort des patients The incidence of deep venous thrombosis ( DVT ) was assessed in a series of 78 patients undergoing major surgical operations to compare the prophylactic effectiveness of intermittent sequential pneumatic compression alone with the simultaneous use of graduated compression stockings and intermittent sequential pneumatic compression . The diagnosis of DVT was determined with the I-125 fibrinogen-uptake test , Doppler ultrasound , maximum venous outflow by strain-gauge plethysmography , and contrast venography . The incidence of DVT in nonstockinged legs was 9 % while that in the stockinged legs was 1 % . The simultaneous use of graduated elastic compression stockings and intermittent pneumatic compression is more effective than pneumatic compression alone in the prevention of postoperative DVT The incidence of deep venous thrombosis ( DVT ) was studied by the 125I‐fibrinogen technique in 70 patients who had had major abdominal operations and who were wearing graduated static compression stockings on one leg , the patient 's other leg being used as a control . In the whole group 7 patients developed bilateral DVT , 19 patients developed unilateral DVT in the control leg and only one patient developed unilateral DVT in the stockinged leg . The difference between stockinged and control legs was highly significant ( P = 0·0003 ) . In the 19 patients with malignant disease the incidence of DVT in the stockinged leg remained significantly less ( P = 0·037 ) . It is concluded that graduated static compression stockings do reduce the incidence of postoperative deep venous thrombosis Objective : To assess intermittent pneumatic compression ( IPC ) in the prevention of venous thromboembolism ( VTE ) . Methods : The authors r and omly allocated patients with a documented intracerebral hemorrhage ( ICH ) to elastic stockings ( ES ) alone or combined with IPC . The primary outcome was a combined criteria assessed at day 10 : a symptomatic and well-documented VTE , or a death arising before day 10 and related to pulmonary embolism ( PE ) , or an asymptomatic deep vein thrombosis ( DVT ) of the lower limbs detected by compression ultrasonography ( CUS ) . Outcome assessment was blinded . Results : One hundred fifty-one patients were r and omized ; 133 ( 88 % ) patients were evaluated at day 10 . No clinical suspicion of VTE arose before day 10 . Fourteen patients died before having a CUS but no death was definitely related to PE . Fourteen asymptomatic DVT were detected by CUS : three ( 4.7 % ) in the ES + IPC group ( all distal ) and 11 ( 15.9 % ) in the ES group ( three proximal and eight distal ) . ES combined with IPC is associated with a reduced risk of asymptomatic DVT compared to ES alone : relative risk , 0.29 ( 95 % CI 0.08 to 1.00 ) . Conclusions : Asymptomatic deep vein thrombosis ( DVT ) was detected at day 10 in 15.9 % of patients wearing elastic stockings alone . Intermittent pneumatic compression significantly decreased the occurrence of asymptomatic DVT for patients with intracerebral hemorrhage |
759 | 31,821,362 | Decreased omentin-1 concentrations may be an important indicator for gestational diabetes mellitus and type 2 diabetes mellitus . | OBJECTIVE Previous studies found inconsistent results on the relationship between diabetes mellitus and concentrations of omentin-1 .
This study performed a systematic review and meta- analysis to summarize previous findings on this relationship . | Background Recent studies have shown that omentin-1 derived from adipokines can affect physiological regulations and some metabolic dis-eases such as type 2 diabetes mellitus ( T2DM ) . Methods The purpose of this study was to examine the impact of 12 weeks of aerobic ( cycle ergometer ) , resistance , and combined exercises on omentin-1 level , glucose and insulin resistance indices in overweight middle age women with T2DM . In this study , 60 overweight middle age diabetic women were selected using simple r and om sampling and they were assigned to three groups of aerobic exercise ( n=12 ) , resistant exercise ( n=12 ) and combined exercise ( n=13 ) , and one control group ( n=15 ) . Exercises were done in a three times per week sessions for a total of 12 weeks . Blood sample s were collected before each exercise session and 24 hours after of the last session . Results Present study showed that fasting blood sugar decreased significantly in all intervention groups , while homeostasis model assessment of insulin resistance ( HOMA-IR ) decreased only in the aerobic and combined exercises groups . Furthermore , there was a significant increase in the omentin-1 level only in the combined exercise group . Conclusion Compared to aerobic and resistance exercises , 12 weeks of combined exercise was more efficient in improving HOMA-IR and increasing serum omentin-1 among women with T2DM This prospect i ve study aim ed to present the reference range of amniotic fluid glucose ( AFglu ) among second trimester pregnant women in southern Thail and , to evaluate the possibility of predicting subsequent gestational diabetes mellitus ( GDM ) using AFglu , and to estimate AFglu cut-off levels for identifying pregnancies at high or low risk for subsequent GDM in singleton pregnancies undergoing genetic amniocentesis due to advanced maternal age . A total of 438 eligible pregnant women were analysed , among whom 58 were subsequently diagnosed as having GDM . The reference range that included the central 95 % of AFglu values at 16 , 17 and 18 weeks of gestation in women not subsequently developing GDM was determined from a linear regression model . Logistic regression was used to identify predictors of subsequent GDM . Odds ratio of subsequent diagnosed GDM participant increased by 7 % for each 1 mg/dl increase in AFglu . Risk of subsequent GDM was also increased in women aged over 36 years and in 17–18 weeks compared to 16 weeks of gestation . Depending on gestational and maternal age , AFglu levels above 51 to 75 mg/dl were at elevated risk of subsequent GDM ( likelihood ratio 2.38 ) . We conclude that AFglu tended to decrease with increasing of gestational age . Gestational age and maternal age accompanied with elevated AFglu are predictive factors for subsequent GDM OBJECTIVE Omentin is a protein expressed and secreted from visceral but not subcutaneous adipose tissue , which increases insulin sensitivity in human adipocytes . However , its pathophysiologic role in humans remains largely unknown . The objective of this study is to assess plasma omentin-1 levels in patients with type 2 diabetes mellitus ( T2DM ) and matched control subjects and to investigate the effects of liraglutide on plasma omentin-1 levels in patients with T2DM . PATIENTS AND METHODS Thirty T2DM patients with poor glycemic control after more than 3 months of treatment with one or two OHA(s ) ( T2DM ) , and 30 matched normal glycaemic controls ( NGT ) participated in the study . The T2DM group was given an injection of liraglutide once-daily for 16 weeks . Plasma omentin-1 levels were measured by enzyme-linked immunosorbent assay and the relationship between plasma omentin-1 levels and metabolic parameters was also analyzed . RESULTS Plasma omentin-1 levels were lower in T2DM than in the control ( 19.3 ± 4.0 μg/L vs. 26.4 ± 6.0 μg/L , P < 0.01 ) . Plasma omentin-1 levels increased significantly in T2DM patients after treatment with liraglutide compared with pre-treatment ( 19.3 ± 4.0 μg/L vs. 21.2 ± 3 . 9 μg/L , P < 0.01 ) . In all diabetic patients , multiple regression analysis showed that FINS and HOMA-IR were independently associated with plasma omentin-1 levels . CONCLUSIONS In T2DM patients , plasma omentin-1 levels decreased , but significantly increased after the treatment with liraglutide and metformin . These data suggest that liraglutide may play a role in increasing omentin-1 levels in T2DM patients AIMS To assess the effects of two commonly used oral hypoglycemic medications metformin and pioglitazone on serum concentrations of omentin and leptin in patients with newly diagnosed type 2 diabetes . METHODS In a clinical trial setting ( NCT01593371 ) , patients were r and omly allocated to either metformin 1000 mg daily ( n=41 ) , or pioglitazone 30 mg daily ( n=50 ) . Serum concentrations of omentin and leptin were measured at baseline and after 12weeks . Patients ' weight , waist circumference , blood pressure , fasting plasma glucose , fasting insulin , HbA1c , highly sensitive C-reactive protein , and serum lipids were also measured at the two visits . RESULTS Baseline concentrations of omentin and leptin were not different between the two arms of the trial . After three months , metformin decreased both omentin and leptin concentrations in women , and leptin concentrations only in men . On the other h and , pioglitazone reduced both adipokines only in women , but not men . Univariate and multivariate ANCOVA models revealed that both interventions are equally effective in reducing omentin concentration ( p=0.497 for women and 0.344 for men in multivariate models controlling for the effects of confounding variables ) . Similarly , neither medication was more effective in reducing leptin concentrations after three months ( p=0.822 for women and 0.441 for men in multivariate models ) . CONCLUSIONS Metformin and pioglitazone at pharmacologic doses are equally effective in alteration of serum omentin and leptin concentrations in patients with diabetes , albeit sex differences in response to medications exist . Implication of these findings on long term management and complication prevention of diabetes needs to be eluci date BACKGROUND Weight loss is often key in the management of obese or overweight patients with type 2 diabetes , yet few treatments for diabetes achieve clinical ly meaningful weight loss . We aim ed to assess the efficacy , tolerability , and safety of treatment with MEDI0382 , a balanced glucagon-like peptide-1 and glucagon receptor dual agonist developed to provide glycaemic control and weight loss , in patients with type 2 diabetes . METHODS This r and omised , placebo-controlled , double-blind , combined multiple-ascending dose ( MAD ) and phase 2a study was done at 11 study sites ( hospitals and contract research organisations ) in Germany . We enrolled patients aged 18 - 65 years with controlled type 2 diabetes ( glycated haemoglobin A1c [ HbA1c ] levels of 6·5 - 8·5 % at screening ) and a body-mass index between 27 kg/m2 and 40 kg/m2 . An interactive web-response system was used to r and omly assign patients to receive MEDI0382 or placebo . Patients were r and omly assigned 2:1 in cohorts A-C and 3:1 in cohorts D and E in the MAD portion of the study , and 1:1 in the phase 2a portion . R and omisation was done by a contracted third-party operator who was not involved in the clinical operations of the study . The pharmacists , participants , and study site personnel involved in treating and assessing participants were masked to treatment allocation . Patients received once-daily subcutaneous injections of the study drug at doses of no more than 300 μg for 22 days or less in the MAD portion of the study , and a dose of no more than 200 μg for 41 days or less in the phase 2a portion . The two primary endpoints of the phase 2a portion were the change from baseline to day 41 in glucose area under the curve at 0 - 4 h ( AUC0 - 4 h ) after a mixed-meal tolerance test ( MMTT ) , assessed in all participants who received at least one dose of study drug and whose measurements were taken at baseline and day 41 , and change from baseline in bodyweight , assessed in the intention-to-treat ( ITT ) population . Safety analyses were done in all participants who received any study drug analysed according to the treatment they received . This study is registered with Clinical Trials.gov , number NCT02548585 . FINDINGS Patients were recruited between Dec 9 , 2015 , and Feb 24 , 2017 . 61 patients were r and omly assigned to the MAD part of the study ( 42 to MEDI0382 and 19 to placebo ) . 51 patients were r and omly assigned to the phase 2a part , of whom 25 were r and omly assigned to MEDI0382 and 26 to placebo . In the phase 2a study , three patients in the MEDI0382 group and one in the placebo group discontinued , all as a result of adverse events . 22 ( 88 % ) patients in the MEDI0382 group and 25 ( 96 % ) in the placebo group received at least one dose and had measurements taken at baseline and day 41 . Glucose AUC0 - 4 h post MMTT decreased significantly with MEDI0382 versus placebo ( least squares [ LS ] mean -32·78 % [ 90 % CI -36·98 to -28·57 ] vs -10·16 % [ -14·10 to -6·21 ] , and the mean difference was -22·62 % [ -28·40 to -16·85 ] ; p<0·0001 ) . In the ITT population , reduction in bodyweight was significantly greater with MEDI0382 than with placebo ( LS mean -3·84 kg [ 90 % CI -4·55 to -3·12 ] vs -1·70 kg [ -2·40 to -1·01 ] and mean difference of 2·14 kg [ -3·13 to -1·31 ] ; p=0·0008 ) . The proportion of patients who had a treatment-emergent adverse event ( TEAE ) was similar between treatment groups ( 22 [ 88 % ] of 25 in the MEDI0382 group vs 23 [ 88 % ] of 26 in the placebo group ) ; gastrointestinal disorders ( 18 [ 72 % ] vs 13 [ 40 % ] ) and decreased appetite ( five [ 20 % ] vs none ) occurred more frequently with MEDI0382 than placebo . No participants in the MEDI0382 group had a grade 3 or worse TEAE ( vs two [ 8 % ] in the placebo group ) . INTERPRETATION MEDI0382 has the potential to deliver clinical ly meaningful reductions in blood glucose and bodyweight in obese or overweight individuals with type 2 diabetes . FUNDING MedImmune BACKGROUND Glucagon-like peptide 1 receptor agonists differ in chemical structure , duration of action , and in their effects on clinical outcomes . The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown . We aim ed to determine the safety and efficacy of albiglutide in preventing cardiovascular death , myocardial infa rct ion , or stroke . METHODS We did a double-blind , r and omised , placebo-controlled trial in 610 sites across 28 countries . We r and omly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease ( at a 1:1 ratio ) to groups that either received a subcutaneous injection of albiglutide ( 30 - 50 mg , based on glycaemic response and tolerability ) or of a matched volume of placebo once a week , in addition to their st and ard care . Investigators used an interactive voice or web response system to obtain treatment assignment , and patients and all study investigators were masked to their treatment allocation . We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death , myocardial infa rct ion , or stroke , which was assessed in the intention-to-treat population . If non-inferiority was confirmed by an upper limit of the 95 % CI for a hazard ratio of less than 1·30 , closed testing for superiority was prespecified . This study is registered with Clinical Trials.gov , number NCT02465515 . FINDINGS Patients were screened between July 1 , 2015 , and Nov 24 , 2016 . 10 793 patients were screened and 9463 participants were enrolled and r and omly assigned to groups : 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo . On Nov 8 , 2017 , it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued , and participants returned for a final visit and discontinuation from study treatment ; the last patient visit was on March 12 , 2018 . These 9463 patients , the intention-to-treat population , were evaluated for a median duration of 1·6 years and were assessed for the primary outcome . The primary composite outcome occurred in 338 ( 7 % ) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 ( 9 % ) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group ( hazard ratio 0·78 , 95 % CI 0·68 - 0·90 ) , which indicated that albiglutide was superior to placebo ( p<0·0001 for non-inferiority ; p=0·0006 for superiority ) . The incidence of acute pancreatitis ( ten patients in the albiglutide group and seven patients in the placebo group ) , pancreatic cancer ( six patients in the albiglutide group and five patients in the placebo group ) , medullary thyroid carcinoma ( zero patients in both groups ) , and other serious adverse events did not differ between the two groups . There were three ( < 1 % ) deaths in the placebo group that were assessed by investigators , who were masked to study drug assignment , to be treatment-related and two ( < 1 % ) deaths in the albiglutide group . INTERPRETATION In patients with type 2 diabetes and cardiovascular disease , albiglutide was superior to placebo with respect to major adverse cardiovascular events . Evidence -based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes . FUNDING GlaxoSmithKline BACKGROUND There is a direct relationship between bodyweight and risk of diabetes . Lorcaserin , a selective serotonin 2C receptor agonist that suppresses appetite , has been shown to facilitate sustained weight loss in obese or overweight patients . We aim ed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission . METHODS In this r and omised , double-blind , placebo-controlled trial done in eight countries , we recruited overweight or obese patients ( body-mass index ≥27 kg/m2 ) with or at high risk for atherosclerotic vascular disease . Eligible patients were aged 40 years or older ; patients at high risk for atherosclerotic vascular disease had to be aged 50 years or older with diabetes and at least one other risk factor . Patients were r and omly assigned to receive either lorcaserin ( 10 mg twice daily ) or matching placebo . Additionally , all patients had access to a st and ardised weight management programme based on lifestyle modification . The prespecified primary metabolic efficacy endpoint of time to incident diabetes was assessed in patients with prediabetes at baseline . The prespecified secondary outcomes for efficacy were incident diabetes in all patients without diabetes , achievement of normoglycaemia in patients with prediabetes , and change in glycated haemoglobin ( HbA1c ) in patients with diabetes . Hypoglycaemia was a prespecified safety outcome . Analysis was by intention to treat , using Cox proportional hazard models for time-to-event analyses . This trial is registered with Clinical Trials.gov , number NCT02019264 . FINDINGS Between Feb 7 , 2014 , and Nov 20 , 2015 , 12 000 patients were r and omly assigned to lorcaserin or placebo ( 6000 patients in each group ) and followed up for a median of 3·3 years ( IQR 3·0 - 3·5 ) . At baseline , 6816 patients ( 56·8 % ) had diabetes , 3991 ( 33·3 % ) prediabetes , and 1193 ( 9·9 % ) normoglycaemia . At 1 year , patients treated with lorcaserin had a net weight loss beyond placebo of 2·6 kg ( 95 % CI 2·3 - 2·9 ) for those with diabetes , 2·8 kg ( 2·5 - 3·2 ) for those with prediabetes , and 3·3 kg ( 2·6 - 4·0 ) for those with normoglycaemia ( p<0·0001 for all analyses ) . Lorcaserin reduced the risk of incident diabetes by 19 % in patients with prediabetes ( 172 [ 8·5 % ] of 2015 vs 204 [ 10·3 % ] of 1976 ; hazard ratio 0·81 , 95 % CI 0·66 - 0·99 ; p=0·038 ) and by 23 % in patients without diabetes ( 174 [ 6·7 % ] of 2615 vs 215 [ 8·4 % ] of 2569 ; 0·77 , 0·63 - 0·94 ; p=0·012 ) . Lorcaserin result ed in a non-significant increase in the rate of achievement of normoglycaemia in patients with prediabetes ( 185 [ 9·2 % ] vs 151 [ 7·6 % ] ; 1·20 , 0·97 - 1·49 ; p=0·093 ) . In patients with diabetes , lorcaserin result ed in a reduction of 0·33 % ( 95 % CI 0·29 - 0·38 ; p<0·0001 ) in HbA1c compared with placebo at 1 year from a mean baseline of 53 mmol/mol ( 7·0 % ) . In patients with diabetes at baseline , severe hypoglycaemia with serious complications was rare , but more common with lorcaserin ( 12 [ 0·4 % ] vs four [ 0·1 % ] events ; p=0·054 ) . INTERPRETATION Lorcaserin decreases risk for incident diabetes , induces remission of hyperglycaemia , and reduces the risk of microvascular complications in obese and overweight patients , supporting the role of lorcaserin as an adjunct to lifestyle modification for chronic management of weight and metabolic health . FUNDING Eisai |
760 | 29,214,325 | The review showed differences in each step of the procedure , in perioperative care , in anesthesia and in surgeon ’ experience .
Conclusion Our results highlight the problems concerning AC with the great range in postoperative outcomes .
There is diversity in the anatomical structures used in the repair , in perioperative care and in the procedure itself | Introduction Anterior colporrhaphy ( AC ) is considered a st and ard procedure and is performed all over the world .
However , not a single step of the procedure has ever been truly st and ardized and the rates of failure show a wide range in the literature from 0 % up to 92 % .
The aim of this systematic review was to evaluate the differences in technique and procedure worldwide . | Background : The aim of this study is to evaluate the outcome of an innovative , minimally invasive sling technique with autologous tissue in women with concomitant incontinence and anterior vaginal wall prolapse ( AVWP ) . Material s and Methods : Fifty-six women with stress urinary incontinence ( SUI ) or mixed urinary incontinence and AVWP were r and omly assigned into two groups : In Group A ( 26 patients ) , anterior colporrhaphy ( Kelly placation ) and sling placement using a strip of anterior vaginal wall were performed , and in Group B ( 30 patients ) , transvaginal mesh correction of AVWP and tension-free vaginal tape ( TVT ) insertion ( retropubic – craniocaudal route ) using polypropylene mesh were carried out . The patients were followed-up for over 18 months and were assessed objective ly using a 48 h frequency-volume chart , a 48 h pad test and a st and ardized stress test . Related surgical complications and outcomes were recorded and compared . Results : Surgical cure rates for Group A and Group B at the first ( 3 days ) and last ( 18 months ) post-operative visits were 62 % and 84 % ; and 54 % , and 72 % , respectively ( P = 0.09 and 0.31 ) . Complications occurred in 9 patients ( 44 % ) of Group B , but only 3 patients ( 12 % ) in Group A. Conclusion : Vaginal sling surgery using an anterior vaginal wall strip can improve SUI and in comparison with propylene mesh is associated with lower complication rates . Although , the surgical success rate of this technique is lower than T-Sling , larger studies with selected patients will help assess the suitable patients for this pelvic reconstructive surgery OBJECTIVE : To compare anatomical and patient-reported outcomes at 12 months postoperatively for women who had anterior compartment pelvic organ prolapse ( POP ) surgery using a repair augmented with porcine small intestine submucosa mesh ( Mesh Group ) compared with those who had a native tissue repair ( No Mesh Group ) . METHODS : This was a r and omized controlled trial with 12 months follow-up . The surgical procedure was identical in both groups except for the placement of intervening mesh . The primary outcome was anatomical “ cure ” ( Ba of −1 or less on Pelvic Organ Prolapse Quantification [ POP-Q ] ) . Secondary outcomes included POP-Q stage , patient-reported outcomes , and patient satisfaction . The study was powered to detect a 40 % difference at 80 % power ( & agr;=0.05 ) . RESULTS : Fifty-seven women were r and omized ( 28 to Mesh Group , 29 to No Mesh Group ) . Forty-five ( 79 % ) underwent concomitant surgery . At the 12-month follow-up , 56 % ( 15/27 ) in the Mesh Group and 61 % ( 17/28 ) in the No Mesh Group were considered cured ( relative risk 0.90 , 95 % confidence interval 0.52–1.54 ) . There were no significant differences between groups in recurrent or persistent prolapse ( 7 % in each group ) nor in patient-reported outcomes at 12 months . Pelvic girdle pain occurred in 4 of 27 in the Mesh Group and 3 of 28 in the No Mesh Group . CONCLUSION : No significant differences were observed in anatomical or patient-reported outcomes outcome parameters at 12 months after correction of symptomatic anterior POP by mesh or no mesh repair . In our study , porcine small intestine submucosa mesh did not confer additional benefit over a native tissue repair . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT0095544 . LEVEL OF EVEDIENCE : Introduction and hypothesisTo compare the efficacy of a collagen-coated polypropylene mesh and anterior colporrhaphy in the treatment of stage 2 or more anterior vaginal wall prolapse . Methods Prospect i ve , r and omized , multicenter study conducted between April 2005 and December 2009 . The principal endpoint was the recurrence rate of stage 2 or more anterior vaginal wall prolapse 12 months after surgery . Secondary endpoints consisted of functional results and mesh-related morbidity . Results One hundred and forty-seven patients were included , r and omized and analyzed : 72 in the anterior colporrhaphy group and 75 in the mesh group . The anatomical success rate was significantly higher in the mesh group ( 89 % ) than in the colporrhaphy group ( 64 % ) ( p = 0.0006 ) . Anatomical and functional recurrence was also less frequent in the mesh group ( 31.3 % vs 52.2 % , p = 0.007 ) . Two patients ( 2.8 % ) were reoperated on in the colporrhaphy group for anterior vaginal wall prolapse recurrence . No significant difference was noted regarding minor complications . An erosion rate of 9.5 % was noted . De novo dyspareunia occurred in 1/14 patients in the colporrhaphy group and in 3/13 patients in the mesh group . An analysis of the quality of life question naires showed an overall improvement in both groups , with no statistical difference between them . Satisfaction rates were high in both groups ( 92 % in the colporrhaphy group and 96 % in the mesh group ) . Conclusion Trans-obturator Ugytex ® mesh used to treat anterior vaginal wall prolapse gives better 1-year anatomical results than traditional anterior colporrhaphy , but with small a increase in morbidity in the mesh group Introduction and hypothesisThis trial aim ed to compare the outcomes of native vaginal tissue repair versus polypropylene mesh repair for the treatment of severe genital prolapse . Methods This multicenter r and omized trial included 184 women , with POP-Q stage 3 or 4 . They were r and omly assigned to undergo surgical treatment using native tissue repair ( n = 90 ) or synthetic mesh repair ( n = 94 ) . Native tissue repair surgery was performed according to site-specific defects , including sacrospinous ligament fixation for apical defects . Mesh repair ( Prolift ™ ) was performed in accordance with manufacturer recommendations . Hysterectomy was performed in all cases of uterine prolapse . Statistical tests were used to compare between-group and within-group differences before the surgery and at 1-year follow-up . We considered cure to have occurred when the POP-Q point evaluation was equal to or less than 0 and POP-Q point C better than or equal to half the total vaginal length ( TVL ) after 1 year . The patients answered the Prolapse Quality -of-Life Question naire ( PQoL ) and the Sexual Quotient Female Version ( QS-F ) question naire . Results Both groups were homogeneous preoperatively . There were no differences between the groups in operative time , complications or pain . At 1-year follow-up , anatomical cure rates were better in the mesh group in the anterior compartment ( p = 0.019 ) . Significant improvement in PQoL scores at 1-year follow up were observed in each group ; between-group comparisons of changes in PQoL scores revealed greater improvement in the mesh group . Conclusion Both techniques were effective . Anatomical efficacy was superior in the mesh group regarding the anterior compartment ; quality of life changes were also greater in the mesh group . Complications were significantly higher in the mesh group Introduction and hypothesisThe aim of the study was to compare the efficacy and safety of transvaginal trocar-guided polypropylene mesh insertion with traditional colporrhaphy for treatment of anterior vaginal wall prolapse . Methods This is a r and omized controlled trial in which women with advanced anterior vaginal wall prolapse , at least stage II with Ba ≥ + 1 cm according to the Pelvic Organ Prolapse Quantification ( POP-Q ) classification , were r and omly assigned to have either anterior colporrhaphy ( n = 39 ) or repair using trocar-guided transvaginal mesh ( n = 40 ) . The primary outcome was objective cure rate of the anterior compartment ( point Ba ) assessed at the 12-month follow-up visit , with stages 0 and I defined as anatomical success . Secondary outcomes included quantification of other vaginal compartments ( POP-Q points ) , comparison of quality of life by the prolapse quality of life ( P-QOL ) question naire , and complication rate between the groups after 1 year . Study power was fixed as 80 % with 5 % cutoff point ( p < 0.05 ) for statistical significance . Results The groups were similar regarding demographic and clinical preoperative parameters . Anatomical success rates for colporrhaphy and repair with mesh placement groups were 56.4 vs 82.5 % ( 95 % confidence interval 0.068–0.54 ) , respectively , and the difference between the groups was statistically significant ( p = 0.018 ) . Similar total complication rates were observed in both groups , with tape exposure observed in 5 % of the patients . There was a significant improvement in all P-QOL domains as a result of both procedures ( p < 0.001 ) , but they were not distinct between groups ( p > 0.05 ) . Conclusions Trocar-guided transvaginal synthetic mesh for advanced anterior POP repair is associated with a higher anatomical success rate for the anterior compartment compared with traditional colporrhaphy . Quality of life equally improved after both techniques . However , the trial failed to detect differences in P-QOL scores and complication rates between the groups OBJECTIVE To compare the use of polypropylene mesh ( PM ) and the traditional anterior vaginal wall colporraphy in women with anterior vaginal wall prolapse ( AVWP ) using objective and subjective tests and evaluation of quality of life ( QoL ) . MATERIAL S AND METHODS One hundred women were r and omly distributed in two preoperatory groups . The first group ( mesh ) ( n = 45 ) received a PM implant and the control group ( n = 55 ) was su bmi tted to traditional colporraphy . Postoperatory follow-up was done after 12 months . The primary objective was the correction of the Ba point ≤ -2 POP-Q ( Pelvic Organ Prolapse Quantification System ) and the secondary objective was the improvement of vaginal symptoms and QoL through ICIQ-VS ( International Consultation on Incontinence Question naire - Vaginal Symptoms ) . Complications related to the use of PM or not were also described . RESULTS There was a significant difference between all POP-Q measures of pre- and postoperatory periods of each group in particular . There was a significant difference of the Ba point of the postoperatory period between the Mesh and Control group . The mean of Ba point in the Mesh group was statistically lower than of the Control group , depicting the better anatomical result of the first group . Both techniques improved vaginal symptoms and QoL. The most frequent complication of the Mesh group was prepubic hematoma in the perioperative period . In 9.3 % of the cases treated with mesh it was observed PM exposition at the anterior vaginal wall after 12 months , being most of them treated clinical ly . CONCLUSION The treatment of AVWP significantly improved the Ba point in the Mesh group in comparison to the Control group . There were no differences of the vaginal symptoms and QoL between the two groups after 12 months . There were few and low grade complications on both groups The aim of this study was to compare the efficiency of polypropylene mesh surgery with the site-specific repair surgeries in the treatment of cystocoeles . We r and omized 90 patients into two groups according to a computer-based program . After a 12-month ( mean ) follow up , we noticed that the polypropylene mesh surgery yielded good anatomical results . Acceptable anatomical cure rates were 91 and 72 % in the mesh surgery group and site-specific surgery group , respectively . There were three cases ( 6.9 % ) of mesh erosion . One case of urinary retention and two cases of de novo dyspareunia were seen in the mesh surgery group . De novo stress urinary incontinence developed in three patients in the site-specific surgery group . We concluded that surgery with light polypropylene mesh ( Sofradim ® , Parietene ) is superior to the site-specific surgery in the treatment of cystocoeles OBJECTIVE : To present 3-month outcomes of a double-blind , multicenter r and omized controlled trial comparing traditional vaginal prolapse surgery without mesh with vaginal surgery with mesh . METHODS : Women with pelvic organ prolapse quantification prolapse stages 2–4 were r and omized to vaginal colpopexy repair with mesh or traditional vaginal colpopexy without mesh . The primary outcome measure was objective treatment success ( pelvic organ prolapse quantification stage 1 or lower ) at 3 months . Secondary outcome measures included quality -of-life variables and complication rates . RESULTS : Sixty-five women were recruited from January 2007 to August 2009 , when the study was halted due to predetermined stopping criteria for vaginal mesh erosion at a median follow-up of 9.7 months ( range , 2.4–26.7 months ) . Thirty-two women underwent mesh colpopexy ( 24 anterior mesh , eight total mesh ) , and 33 women had vaginal colpopexies without mesh ( primarily uterosacral ligament suspension ) and concurrent colporrhaphy . There were no statistically significant baseline differences between the mesh and no-mesh groups with respect to demographics , menopausal status , and race . Analysis of the mesh and no-mesh women found no difference with respect to overall recurrence ( mesh : 19 [ 59.4 % ] compared with no mesh : 24 [ 70.4 % ] , P=.28 ) . There were five ( 15.6 % ) vaginal mesh erosions . Two cystotomies and one blood transfusion occurred in the mesh group only . Subjective cure of bulge symptoms was noted in 93.3 % of mesh patients and 100 % of no-mesh patients . Furthermore , subjective quality -of-life measurements did not differ between the two groups at baseline or 3 months postoperatively . CONCLUSION : At 3 months , there is a high vaginal mesh erosion rate ( 15.6 % ) with no difference in overall objective and subjective cure rates . This study questions the value of additive synthetic polypropylene mesh for vaginal prolapse repairs . CLINICAL TRIAL REGISTRATION : Clinical trials.gov , www . clinical trials.gov , NCT00475540 . LEVEL OF EVIDENCE : One hundred seven consecutive patients with clinical and urodynamic findings of genuine stress incontinence not previously treated were prospect ively allocated in a r and omized manner to one of three surgical procedures : anterior colporrhaphy , revised Pereyra procedure , or Burch retropubic urethropexy . R and omization included the surgical procedure and choice of surgeon ( one of the three authors ) . Clinical and urodynamic evaluations were repeated at 3 months and 1 year after surgery . Differences in cure rates among the three procedures at the 3-month postoperative evaluation were insignificant ( 82 % , 84 % , and 92 % for the anterior colporrhaphy , Pereyra , and Burch respectively ) but became statistically significant at the 1 year postoperative evaluation ( cure rates of 65 % , 72 % , and 91 % for the anterior colporrhaphy , Pereyra , and Burch respectively , p less than 0.05 ) . In our h and s the Burch procedure stabilized the urethrovesical junction and prevented its descent during straining ( evaluated by a postoperative Q-tip test ) more effectively than either the Pereyra or anterior colporrhaphy . No procedure result ed in severe postoperative voiding difficulties . The present prospect i ve r and omized study demonstrates that in our h and s the abdominal retropubic operation for genuine stress incontinence in patients not previously operated on results in a higher cure rate when compared with anterior colporrhaphy or Pereyra procedure Introduction and hypothesisThe effect of a Pelvicol ® graft compared with a conventional anterior vaginal repair was evaluated in this r and omised controlled study . Methods Only patients with a stage II or higher ( Ba ≥ −1 ) defect were included . Results Thirty-one patients were allocated to a conventional anterior repair ; 30 to Pelvicol ® graft . At 12 months follow-up , four patients among controls ( 15 % ) and two in the graft group ( 7 % ) had objective recurrence . Among controls , the difference at 3 months follow-up in Ba was 6.0 cm when compared with the position of Ba prior to surgery . In the graft group , the difference was 7.0 cm ( P < 0.05 ) . This difference was still present at 12 months follow-up ( 6.0 vs. 7.0 cm ; P < 0.05 ) . Conclusions The implantation of a Pelvicol ® graft does not improve the POP-Q stage Surgery and other invasive therapies are complex interventions , the assessment of which is challenged by factors that depend on operator , team , and setting , such as learning curves , quality variations , and perception of equipoise . We propose recommendations for the assessment of surgery based on a five-stage description of the surgical development process . We also encourage the widespread use of prospect i ve data bases and registries . Reports of new techniques should be registered as a professional duty , anonymously if necessary when outcomes are adverse . Case series studies should be replaced by prospect i ve development studies for early technical modifications and by prospect i ve research data bases for later pre-trial evaluation . Protocol s for these studies should be registered publicly . Statistical process control techniques can be useful in both early and late assessment . R and omised trials should be used whenever possible to investigate efficacy , but adequate pre-trial data are essential to allow power calculations , clarify the definition and indications of the intervention , and develop quality measures . Difficulties in doing r and omised clinical trials should be addressed by measures to evaluate learning curves and alleviate equipoise problems . Alternative prospect i ve design s , such as interrupted time series studies , should be used when r and omised trials are not feasible . Established procedures should be monitored with prospect i ve data bases to analyse outcome variations and to identify late and rare events . Achievement of improved design , conduct , and reporting of surgical research will need concerted action by editors , funders of health care and research , regulatory bodies , and professional societies Summary To compare the effectiveness of polyglactin mesh , and polydioxanone or polyglactin sutures in women having pelvic organ prolapse surgery . R and omised controlled trial with a factorial 2(2 design of polyglactin mesh or not , and polydioxanone or polyglactin suture . Outcomes were assessed using question naires at baseline and on the third day and at 6 months after surgery . Women were also examined clinical ly 3 months after surgery . The primary outcome was the subjective improvement in prolapse symptoms and quality of life scores from baseline to 6 months . There was a subjective improvement in the prolapse symptom score from baseline to 6 months after surgery ( mean difference of 9.2 ( 95 % CI for difference 7.2–11.2 , p < 0.001 ) and an improvement in the mean quality of life score over the same period with a reduction of 3.4 ( 95 % CI for difference 2.4–4.3 , p < 0.001 ) . However , there were no significant differences in the mean difference in prolapse symptoms and quality of life ( QoL ) scores according to the r and omised groups . The majority ( 86 % ) of women were satisfied with their surgery . Our study demonstrated that at short-term follow-up , there was no significant difference in the mean differences in prolapse symptoms and QoL scores after surgery using polyglactin mesh or not , polyglactin or polyglactin sutures , but the numbers were too small for a definitive conclusion . Longer-term follow-up and /or a larger trial are required OBJECTIVE : To compare anterior colporrhaphy with and without a tailored mesh . METHODS : Postmenopausal women with anterior vaginal prolapse to the hymen or beyond were r and omly assigned to undergo traditional anterior colporrhaphy alone or reinforced with mesh . The low-weight monofilament polypropylene mesh was self-tailored , having four arms and being placed over the plicated fascia . Before and 2 and 12 months after surgery , participants were evaluated by physical examination , postvoidal residual urine measurement and st and ard questions covering prolapse-related symptoms . The primary outcome was recurrence of anterior vaginal prolapse at 12 months . Secondary outcomes included operative complications , symptom resolution , and postvoidal urine residual volume . RESULTS : Of the 202 women r and omly assigned , 201 were operated on ( 97 without , 104 with mesh ) . Thirty-seven women ( 38.5 % ) in the no-mesh and seven ( 6.7 % ) in the mesh group experienced a recurrence of anterior wall prolapse ( P<.001 ) at 12 months ; as a result , the number needed to treat for benefit was four . The mean ( st and ard deviation ) postvoidal residual urine volume was lower in patients with mesh than in those undergoing the traditional operation : 25 ( 26 ) mL and 41 ( 57 ) mL ( P=.01 ) . Twenty-three women ( 23 % ) with mesh and 9 ( 10 % ) with no mesh reported stress urinary incontinence ( P=.02 ) . In 18 ( 17.3 % ) , exposure of the mesh was noted , mainly asymptomatic . CONCLUSION : Anterior colporrhaphy , reinforced with , tailored mesh significantly reduced the rate of recurrence of anterior vaginal wall prolapse compared with the traditional operation , but was associated more often with stress urinary incontinence . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00420225 LEVEL OF EVIDENCE : OBJECTIVES Our purpose was to determine whether a vaginal or abdominal approach is more effective in correcting uterovaginal prolapse . STUDY DESIGN Eighty-eight women with cervical prolapse to or beyond the hymen or with vaginal vault inversion > 50 % of its length and anterior vaginal wall descent to or beyond the hymen were r and omized to a vaginal versus abdominal surgical approach . Forty-eight women underwent a vaginal approach with bilateral sacrospinous vault suspension and paravaginal repair , and 40 women underwent an abdominal approach with colposacral suspension and paravaginal repair . Ancillary procedures were performed as indicated . Detailed pelvic examination was performed postoperatively by the nonsurgeon coauthor yearly up to 5 years . The women were examined while st and ing during maximum strain . Surgery was classified as optimally effective if the woman remained asymptomatic , the vaginal apex was supported above the levator plate , and no protrusion of any vaginal tissue beyond the hymen occurred . Surgical effectiveness was considered unsatisfactory if the woman was symptomatic , the apex descended > 50 % of its length , or the vaginal wall protruded beyond the hymen . RESULTS Eighty women ( vaginal 42 , abdominal 38 ) were available for evaluation at 1 to 5.5 years ( mean 2.5 years ) . The groups were similar in age , weight , parity , and estrogen status , and 56 % had undergone prior pelvic surgery . There was no significant difference between the groups in morbidity , complications , hemoglobin change , dyspareunia , pain , or hospital stay . The vaginal group had longer catheter use , more urinary tract infections , more incontinence , decreased operative time , and lower hospital charge . Surgical effectiveness was optimal in 29 % of the vaginal group and 58 % of the abdominal group and was unsatisfactory leading to reoperation in 33 % of the vaginal group and 16 % of the abdominal group . The reoperations included procedures for recurrent incontinence in 12 % of the vaginal and 2 % of the abdominal groups . The relative risk of optimal effectiveness by the abdominal route is 2.03 ( 95 % confidence interval 1.22 to 9.83 ) , and the relative risk of unsatisfactory outcome using the vaginal route is 2.11 ( 95 % confidence interval 0.90 to 4.94 ) . CONCLUSIONS Reconstructive pelvic surgery for correction of significant pelvic support defects was more effective with an abdominal approach Objective To compare the effects of vaginal hysterectomy ( combined with anterior and /or posterior colporraphy ) and abdominal sacro‐colpopexy ( with preservation of the uterus ) on urogenital function BACKGROUND The use of st and ardized mesh kits for repair of pelvic-organ prolapse has spread rapidly in recent years , but it is unclear whether this approach results in better outcomes than traditional colporrhaphy . METHODS In this multicenter , parallel-group , r and omized , controlled trial , we compared the use of a trocar-guided , transvaginal polypropylene-mesh repair kit with traditional colporrhaphy in women with prolapse of the anterior vaginal wall ( cystocele ) . The primary outcome was a composite of the objective anatomical design ation of stage 0 ( no prolapse ) or 1 ( position of the anterior vaginal wall more than 1 cm above the hymen ) , according to the Pelvic Organ Prolapse Quantification system , and the subjective absence of symptoms of vaginal bulging 12 months after the surgery . RESULTS Of 389 women who were r and omly assigned to a study treatment , 200 underwent prolapse repair with the transvaginal mesh kit and 189 underwent traditional colporrhaphy . At 1 year , the primary outcome was significantly more common in the women treated with transvaginal mesh repair ( 60.8 % ) than in those who underwent colporrhaphy ( 34.5 % ) ( absolute difference , 26.3 percentage points ; 95 % confidence interval , 15.6 to 37.0 ) . The surgery lasted longer and the rates of intraoperative hemorrhage were higher in the mesh-repair group than in the colporrhaphy group ( P<0.001 for both comparisons ) . Rates of bladder perforation were 3.5 % in the mesh-repair group and 0.5 % in the colporrhaphy group ( P=0.07 ) , and the respective rates of new stress urinary incontinence after surgery were 12.3 % and 6.3 % ( P=0.05 ) . Surgical reintervention to correct mesh exposure during follow-up occurred in 3.2 % of 186 patients in the mesh-repair group . CONCLUSIONS As compared with anterior colporrhaphy , use of a st and ardized , trocar-guided mesh kit for cystocele repair result ed in higher short-term rates of successful treatment but also in higher rates of surgical complications and postoperative adverse events . ( Funded by the Karolinska Institutet and Ethicon ; Clinical Trials.gov number , NCT00566917 . ) OBJECTIVE In a r and omized trial , we compared the success of Burch retropubic urethropexy to the modified anterior colporrhaphy for the treatment of genuine stress urinary incontinence . METHODS Thirty-five patients with stress incontinence were r and omly assigned to undergo Burch retropubic urethropexy or modified anterior colporrhaphy . Subjects had preoperative and 1-year postoperative physical examinations , multichannel urodynamic testing , 20-minute pad test , and subjective grading of incontinence severity with question naires . Data were evaluated using Fisher exact test , Wilcoxon two- sample test , logistic regression analysis , and analysis of variance . RESULTS Objective cure 1 year postoperatively was significantly greater for the women treated by Burch retropubic urethropexy than by modified anterior colporrhaphy ( 16 of 18 [ 89 % ] versus five of 16 [ 31 % ] , relative risk .15 , 95 % confidence interval .04 , .59 ) . Patients ' subjective ratings of incontinence severity 1 year after surgical treatment were significantly lower in women who had Burch retropubic urethropexy . CONCLUSION Burch retropubic urethropexy yields a significantly superior objective cure for genuine stress urinary incontinence than the modified anterior colporrhaphy in a r and omized trial Purpose To compare the clinical effectiveness of anterior colporrhaphy versus mesh repair as surgical management of anterior vaginal prolapse . Methods Of 50 patients with ≥stage II anterior vaginal prolapse on Pelvic Organ Prolapse Quantification ( POPQ ) system who were initially approached , 44 consented and underwent surgery . They were r and omly recruited into two groups . Group I ( 23 patients ) received anterior colporrhaphy , while group II ( 21 patients ) received soft polypropylene mesh ( GYNEMESH*PS , Gynecare , Ethicon , France ) . Clinical assessment took place preoperatively and postoperatively at definite intervals . Functional and anatomical comparisons were based on comparison between preoperative and 24 months postoperative assessment s of symptoms and POPQ stages , respectively . Four patients in total did not complete the follow-up assessment s and were excluded . Results Both groups showed clinical improvement in their symptoms and POPQ staging at the end of the postoperative follow-up period . Improvement , however , was more significant in the repair with mesh group , as patients in this group reported better improvement of their prolapse symptoms , mainly vaginal bulge/pressure sensation ( P < 0.05 ) , and showed better improvement in the anatomical staging , individual POP-Q points Aa and Ba ( P < 0.01 ) , than the anterior colporrhaphy group . Group II also showed more satisfactory outcome with the general POP-Q staging ( P < 0.05 ) than group I , reflecting a better quality of life of the patients in the repair with mesh group . Conclusion Our data shows that repair with mesh is superior to anterior colporrhaphy with more satisfactory outcome to the patients . Due to the small size of our study and uncertainty of the long-term safety and resilience of the mesh , we recommend larger studies to confirm our preliminary results PURPOSE We evaluated the efficacy of the Pelvicol porcine collagen implant for preventing recurrent anterior vaginal wall prolapse in women undergoing primary surgery for pelvic organ prolapse . MATERIAL S AND METHODS This was a prospect i ve , r and omized , multicenter trial in 206 women with stage II or greater anterior vaginal wall prolapse ( point Ba -1 or greater ) according to the pelvic organ prolapse quantification system . The patients were r and omly assigned to undergo anterior vaginal repair or the same procedure with Pelvicol implant reinforcement . SPSS software was used for data analysis . RESULTS A total of 201 women were available for surgical outcome analysis , including 98 and 103 in the implant and no implant groups , respectively . All completed the 1-year followup visit . Most women were satisfied with the postoperative condition with a significant decrease in the visual analog scale score in each group ( p < 0.001 ) . Anatomical anterior recurrence ( point Ba greater than -1 ) was observed in 7 women ( 7 % ) in the implant group and in 20 ( 19 % ) in the other groups ( OR 3.13 , 95 % CI 1.26 - 7.78 , p = 0.019 ) . Additionally , there were 11 women ( 3 and 8 , respectively , or 5 % ) with posterior recurrence and 6 ( 3 per group or 3 % ) with unsatisfactory results at the upper vaginal segment . One patient who received a porcine implant had vaginal extrusion of the mesh 1 month after surgery . CONCLUSIONS Our data show that the Pelvicol implant can be easily and readily used to augment and reinforce anterior colporrhaphy . The prolapse recurrence rate was considerably lower in the implant group compared with outcomes in patients treated with simple anterior repair OBJECTIVE Pelvic organ prolapse is a disorder caused by the imbalance between the forces responsible for supporting the pelvic organs in their normal position and those that tend to expel them from the pelvis . Anterior vaginal wall prolapse , known as cystocele , is the most common form of prolapse and can result from lesions in different topographies of the endopelvic fascia . Currently , a woman has an 11 % risk of being su bmi tted to a surgical procedure to correct pelvic floor disorder , and a 29 % chance of being reoperated due to failure in the first surgery . METHODS A prospect i ve r and omized study was conducted to compare the use of polypropylene mesh with site-specific repair in the surgical treatment of anterior vaginal prolapse . Thirty-two patients aged between 50 and 75 years , who had previous vaginal prolapse at stage III or IV , or prolapse recurrence , were operated . Mean follow-up was 8.5 months . RESULTS The results demonstrate the superiority of the anatomical outcomes with the use of polypropylene mesh over site-specific repair . Regarding surgical morbidity , shorter operative time was observed for the mesh group . CONCLUSION The results observed in this study indicate the superiority of anatomical results obtained with the use of polypropylene mesh over site-specific repair OBJECTIVE The purpose of this study was to compare outcomes after anterior colporrhaphy with the use of 3 different surgical techniques . STUDY DESIGN One hundred fourteen women with anterior vaginal prolapse were r and omly assigned to undergo anterior repair by one of 3 techniques : st and ard , st and ard plus polyglactin 910 mesh , or ultralateral anterior colporrhaphy . Before and after operation , patients underwent physical examination staging of prolapse ; the International Continence Society system was used . Symptoms were assessed by question naire and visual analog scales . We defined " cure " as satisfactory ( stage I ) or optimal ( stage 0 ) outcome at points Aa and Ba . RESULTS Of 114 patients who were originally enrolled , 109 patients underwent operation , and 83 patients ( 76 % ) returned for follow-up . Mean age ( + /- SD ) was 64.7 + /- 11.1 years . At entry , 7 patients ( 7 % ) had stage I anterior vaginal prolapse ; 35 patients ( 37 % ) had stage II anterior vaginal prolapse ; 51 patients ( 54 % ) had stage III anterior vaginal prolapse ; and 2 patients ( 2 % ) had stage IV anterior vaginal prolapse . At a median length of follow-up of 23.3 months , 10 of 33 patients ( 30 % ) who were r and omly assigned to the st and ard anterior colporrhaphy group experienced satisfactory or optimal anatomic results , compared with 11 of 26 patients ( 42 % ) with st and ard plus mesh and with 11 of 24 patients ( 46 % ) with ultralateral anterior colporrhaphy . The severity of symptoms that were related to prolapse improved markedly ( preoperative score , 6.9 + /- 2.7 ; postoperative score , 1.1 + /- 0.8 ) . Twenty-three of 24 patients ( 96 % ) no longer required manual pressure to void after operation . CONCLUSION These 3 techniques of anterior colporrhaphy provided similar anatomic cure rates and symptom resolution for anterior vaginal prolapse repair . The addition of polyglactin 910 mesh did not improve the cure rate compared with st and ard anterior colporrhaphy BACKGROUND Women without stress urinary incontinence undergoing vaginal surgery for pelvic-organ prolapse are at risk for postoperative urinary incontinence . A midurethral sling may be placed at the time of prolapse repair to reduce this risk . METHODS We performed a multicenter trial involving women without symptoms of stress incontinence and with anterior prolapse ( of stage 2 or higher on a Pelvic Organ Prolapse Quantification system examination ) who were planning to undergo vaginal prolapse surgery . Women were r and omly assigned to receive either a midurethral sling or sham incisions during surgery . One primary end point was urinary incontinence or treatment for this condition at 3 months . The second primary end point was the presence of incontinence at 12 months , allowing for subsequent treatment for incontinence . RESULTS Of the 337 women who underwent r and omization , 327 ( 97 % ) completed follow-up at 1 year . At 3 months , the rate of urinary incontinence ( or treatment ) was 23.6 % in the sling group and 49.4 % in the sham group ( P<0.001 ) . At 12 months , urinary incontinence ( allowing for subsequent treatment of incontinence ) was present in 27.3 % and 43.0 % of patients in the sling and sham groups , respectively ( P=0.002 ) . The number needed to treat with a sling to prevent one case of urinary incontinence at 12 months was 6.3 . The rate of bladder perforation was higher in the sling group than in the sham group ( 6.7 % vs. 0 % ) , as were rates of urinary tract infection ( 31.0 % vs. 18.3 % ) , major bleeding complications ( 3.1 % vs. 0 % ) , and incomplete bladder emptying 6 weeks after surgery ( 3.7 % vs. 0 % ) ( P≤0.05 for all comparisons ) . CONCLUSIONS A prophylactic midurethral sling inserted during vaginal prolapse surgery result ed in a lower rate of urinary incontinence at 3 and 12 months but higher rates of adverse events . ( Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women 's Health ; OPUS Clinical Trials.gov number , NCT00460434 . ) OBJECTIVE : To report 2-year outcomes of a r and omized controlled trial comparing st and ard anterior colporrhaphy with reinforced vaginal paravaginal repair using xenograft or synthetic mesh in women with symptomatic anterior vaginal wall prolapse . METHODS : Women with stage II or greater anterior prolapse were r and omly assigned to three groups : anterior colporrhaphy , paravaginal repair with porcine dermis , or polypropylene mesh . Outcomes of prolapse stage , quality of life , degree of bother , and sexual symptoms were assessed by blinded examiners and vali date d measures at 2 years . Anatomic failure was defined as anterior prolapse at stage II or greater . Composite failure was defined as symptoms of “ bulge ” and anterior prolapse at stage II or greater . Power calculations determined 33 participants per arm would detect a 40 % difference in anatomic success between st and ard and grafted repair . & khgr;2 , Mann-Whitney U , and Student 's t tests were used for comparisons . RESULTS : Of the 99 participants enrolled , 78 ( 79 % ) completed a minimum of 2-year follow-up . Those with mesh had a significantly lower anatomic failure rate ( 18 % ) than both the porcine ( 46 % , P=.015 ) and colporrhaphy groups ( 58 % , P=.002 ) . All groups had statistically similar reductions in their prolapse and urinary symptom subscale scores . Composite failure was not statistically different between groups : 13 % colporrhaphy , 12 % porcine , and 4 % mesh . Two reoperations for anterior prolapse occurred in the porcine group . Mesh erosion rates were 14 % for the mesh group . CONCLUSION : Vaginal paravaginal repair with polypropylene mesh has the lowest anatomic failure rate when compared with that with xenograft and anterior colporrhaphy without differences in composite failures . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT0139171 . LEVEL OF EVIDENCE : Objective . To determine the long‐term objective and subjective outcomes of use of a porcine skin graft ( Pelvicol ™ ) compared with conventional colporrhaphy in recurrent pelvic organ prolapse surgery and to analyze risk factors and safety . Design . Open r and omized controlled multicenter study . Setting . Eight Swedish hospitals . Population . 135 consecutive women with recurrent cystocele and /or rectocele admitted for vaginal prolapse surgery ; 132 completed the study , 64 were r and omly allocated to receive conventional colporrhaphy and 68 to Pelvicol . Methods . Conventional anterior and posterior colporrhaphy and colporrhaphy with use of Pelvicol ™ mesh reinforcement . Clinical evaluation by means of pelvic organ prolapse quantification ( POP‐Q ) and symptom question naire preoperatively , three months and three years postoperatively . Main outcome measures . Anatomical and subjective outcome . Recurrence was defined as POP‐Q≥stage 2 . Results . At three‐month follow‐up , early recurrence/surgical failures occurred significantly more often in the Pelvicol ™ group , but at the three‐year follow‐up the recurrence rates were similar . The recurrence rates in the anterior compartment were 57–62 % and 44–23 % in the posterior compartment for the colporrhaphy and Pelvicol ™ groups , respectively . Symptoms were substantially and equally reduced in the two groups after surgery . Sexual activity and function did not seem to be affected adversely in any group . The complication rate was low . Risk factors for anatomical recurrence were age , body mass index and preoperative stage of the prolapse . Conclusions . With the surgical technique used in this study , Pelvicol ™ did not provide advantages over conventional colporrhaphy in recurrent pelvic organ prolapse concerning anatomical and subjective outcomes OBJECTIVE : To compare outcomes of anterior colporrhaphy alone to that reinforced with bovine pericardium graft . METHODS : Women with anterior vaginal wall prolapse were enrolled in a r and omized fashion in this grafted compared with nongrafted repair study . Outcome measures included pelvic organ prolapse quantification data , quality -of-life assessment , healing abnormalities , and complications . RESULTS : Ninety-four patients were enrolled . Seventy-two ( 77 % ) provided 1-year data , and 59 ( 63 % ) supplied 2-year data . Demographics and stage of prolapse were similar between groups at baseline . Postoperative complications consisted basically of low urinary tract infection and were low in both groups ( 10 in bovine pericardium graft and 16 in anterior colporrhaphy alone ) . One year after surgery , successful anterior vaginal wall support was obtained in 85.7 % of the bovine pericardium graft group and 78.4 % of anterior colporrhaphy – alone group ( P=.544 ) . For the cohort that comprised 2-year analyses , the success rate was 76.5 % for the bovine pericardium graft group and 63 % for anterior colporrhaphy – alone group ( P=.509 ) . Postoperative Urogenital Distress Inventory-6 and Pelvic Organ Prolapse – Urinary Incontinence Sexual Function Question naire-12 scores were uniformly improved over baseline in both groups . CONCLUSION : The use of bovine pericardium graft for anterior vaginal prolapse does not have higher complication rates or healing difficulties . At 1- and 2-year follow-up , anterior colporrhaphy with bovine pericardium reinforcement did not show a statistically significant improvement over colporrhaphy alone . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00860912 LEVEL OF EVIDENCE : THE R AND OMIZED controlled trial ( RCT ) , more than any other methodology , can have a powerful and immediate impact on patient care . Ideally , the report of such an evaluation needs to convey to the reader relevant information concerning the design , conduct , analysis , and generalizability of the trial . This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial . Accurate and complete reporting also benefits editors and review ers in their deliberations regarding su bmi tted manuscripts . For RCTs to ultimately benefit patients , the published report should be of the highest possible st and ard Introduction and hypothesisThis study seeks to compare the small intestine submucosa ( SIS ) graft with traditional colporrhaphy ( TC ) for surgical treatment of anterior vaginal prolapse . Methods Subjects were r and omly assigned to SIS ( n = 29 ) or to TC ( n = 27 ) preoperatively and outcomes analyzed at 12 months postoperatively . The primary outcome was the absence of POP-Q stage ≥ II prolapse , and secondary outcome was improvement in quality of life . Data were compared with independent sample s or paired Student ’s t test . Results SIS group had 86.2 % anatomic cure compared to 59.3 % in TC ( p = 0.03 ) . SIS improved point Ba measurement significantly ( −1.93 cm versus −1.37 cm , p = 0.02 ) . Both operations significantly improved quality of life , although there were no differences between the groups . We observed a greater number of complications in the SIS group , with no infections or erosion . Conclusions SIS repair improved point Ba significantly . However , there were no differences observed in quality of life between the techniques OBJECTIVE : To compare efficacy and safety of trocar-guided tension-free vaginal mesh insertion with conventional vaginal prolapse repair in patients with recurrent pelvic organ prolapse . METHODS : Patients with recurrent pelvic organ prolapse stage II or higher were r and omly assigned to either conventional vaginal prolapse surgery or polypropylene mesh insertion . Primary outcome was anatomic failure ( pelvic organ prolapse stage II or higher ) in the treated vaginal compartments . Secondary outcomes were subjective improvement , effects on bother , quality of life , and adverse events . Question naires such as the Incontinence Impact Question naire and Urogenital Distress Inventory were administered at baseline , 6 months , and 12 months . Anatomic outcomes were assessed by an unblinded surgeon . Power calculation with & agr;=0.05 and & bgr;=0.80 indicated that 194 patients were needed . RESULTS : Ninety-seven women underwent conventional repair and 93 mesh repair . The follow-up rate after 12 months was 186 of 190 patients ( 98 % ) . Twelve months postsurgery , anatomic failure in the treated compartment was observed in 38 of 84 patients ( 45.2 % ) in the conventional group and in eight of 83 patients ( 9.6 % ) in the mesh group ( P<.001 ; odds ratio , 7.7 ; 95 % confidence interval , 3.3–18 ) . Patients in either group reported less bulge and overactive bladder symptoms . Subjective improvement was reported by 64 of 80 patients ( 80 % ) in the conventional group compared with 63 of 78 patients ( 81 % ) in the mesh group . Mesh exposure was detected in 14 of 83 patients ( 16.9 % ) . CONCLUSION : At 12 months , the number of anatomic failures observed after tension-free vaginal mesh insertion was less than after conventional vaginal prolapse repair . Symptom decrease and improvement of quality of life were equal in both groups . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00372190 . LEVEL OF EVIDENCE : OBJECTIVE To compare success rates between anterior colporrhaphy and abdominal paravaginal defect repair for treatment of anterior vaginal wall prolapse . METHODS This was a prospect i ve r and omized controlled trial comparing anterior colporrhaphy plus polyglactin 910 mesh ( vaginal ) to paravaginal defect repair ( abdominal ) in women with symptomatic anterior vaginal wall prolapse . Pelvic organ prolapse quantification staging ( POP-Q ) , pelvic floor distress inventory , pelvic floor impact question naire , and pelvic organ prolapse/urinary incontinence sexual question naires were administered pre and post-operatively . Women were followed up to 2 years . The primary outcome was anterior POP-Q stage , with failure defined as ≥stage II . RESULTS We enrolled 70 patients , 35 in each group . Demographic and most peri-operative characteristics were similar between the groups . Mean anterior vaginal wall prolapse repair time ( 39 min ) was shorter for vaginal versus abdominal repair ( 60 min ; P < 0.001 ) , with more concurrent hysterectomies in the vaginal ( 71 % ) versus abdominal group ( 42 % ) , P = 0.01 . At 2 years , objective failure rates for the vaginal and abdominal groups were 32 % and 40 % , respectively , P = 0.56 . Subjective failure rates were lower and similar for both groups . Patient satisfaction rates were 88 % for the vaginal and 73 % for the abdominal group , P = 0.11 . Quality of life question naires showed significant improvement from baseline but no difference between the groups ( P = 0.12 ) . CONCLUSIONS At 2 years follow-up , anterior colporrhaphy with polyglactin 910 mesh and abdominal paravaginal defect repair have similar success rates , with most objective failures being asymptomatic OBJECTIVE Our aim was to evaluate the efficacy of polyglactin 910 mesh in preventing recurrent cystoceles and rectoceles . STUDY DESIGN In a prospect i ve , r and omized , controlled trial , patients undergoing vaginal reconstructive surgery with cystoceles to the hymenal ring and beyond were r and omly selected to undergo anterior and posterior colporrhaphy with or without polyglactin 910 mesh reinforcement . Results were evaluated preoperatively and at 2 , 6 , 12 , and 52 weeks postoperatively . RESULTS A total of 161 women were r and omly selected for this study . One woman was excluded at the time of surgery , and 17 women were lost to follow-up . Eighty women received mesh , and 80 did not . Both groups were found to be equivalent with respect to age , parity , concomitant surgery , and menopausal and hormone replacement status . Preoperatively 49 women had a central cystocele to the hymenal ring and 111 women had cystoceles beyond the introitus ; 91 women had a rectocele to the mid-vaginal plane , 31 to the hymenal ring , and 22 beyond the introitus . After 1 year , 30 ( 43 % ) of 70 subjects without mesh and 18 ( 25 % ) of 73 subjects with mesh had recurrent cystoceles beyond the mid-vaginal plane ( P = .02 ) . Eight women without mesh and 2 women with mesh had recurrent cystoceles to the hymenal ring ( P = .04 ) . No recurrent cystoceles beyond the hymenal ring occurred in either group . Multivariate logistic regression analysis showed concurrent slings to be associated with significantly fewer recurrent cystoceles ( odds ratio , 0.32 ; P = .005 ) , whereas the presence of mesh remained significantly predictive of fewer cystocele recurrences in this analysis . Thirteen recurrent rectoceles were noted 1 year postoperatively , with no differences between groups . CONCLUSION Polyglactin 910 mesh was found to be useful in the prevention of recurrent cystoceles OBJECTIVE To compare the anatomical and functional results of traditional anterior colporrhaphy and polypropylene mesh surgery in cystocele treatment . STUDY DESIGN Prospect i ve study conducted in the Urogynecology Clinic of Etlik Zubeyde Hanim Maternity and Women 's Health Teaching and Research Hospital between June 2006 and February 2007 . Forty patients with stage II and III cystocele according to the Pelvic Organ Prolapse Quantification system were allocated by a computer programme to conventional or mesh surgery . Twenty patients each underwent anterior colporrhaphy ( group I ) or polypropylene mesh ( Sofradim ( ® ) , Parieten ) surgery ( group II ) . Both groups were followed for 12 months . RESULTS At the end of the 12th month , anatomical cure rates were 15/20 ( 75 % ) and 19/20 ( 95 % ) in groups I and II , respectively , and the difference between the two groups was statistically significant ( p<0.05 ) . De novo stress urinary incontinence developed in one patient in group I. Mesh erosion developed postoperatively in three cases ( 15 % ) . CONCLUSION In terms of anatomical cure rates , polypropylene mesh surgery was the more successful treatment option when compared with anterior colporrhaphy at the end of 1 year follow-up Eighty-one women with clinical and urodynamic findings of genuine stress incontinence and genital prolapse were r and omly selected to be surgically treated with either anterior colporrhaphy or Burch colposuspension . Each patient had a complete clinical and urodynamic evaluation before surgery and at 2 months and 3 years after surgery . Differences in cure rates between the two procedures at the 2-month post-operative evaluation were insignificant ; however , at the 3-year post-surgical evaluation , the cure rate of women who had undergone Burch colposuspension was significantly higher than that of women who had undergone anterior colporrhaphy ( cure rates were 88 % and 57 % , respectively ; P < 0.001 ) . The Burch colposuspension was more effective than the anterior colporrhaphy in the stabilization of the bladder base , neck and proximal urethra as confirmed by transvaginal sonography . Post-operative spontaneous voiding was uneventful in both procedures . Results of this study demonstrate that the Burch colposuspension in our h and s was more effective in treating genuine stress incontinence and pelvic relaxation than was anterior colporrhaphy The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials OBJECTIVES : To report 1-year outcomes of a r and omized controlled trial comparing polypropylene mesh – reinforced anterior vaginal prolapse repair with anterior colporrhaphy . METHODS : Seventy-six patients with stage II or greater anterior vaginal prolapse were r and omly assigned to either colporrhaphy or polypropylene mesh repair . The primary outcome was recurrent stage II anterior vaginal prolapse , and secondary outcomes were effects on quality of life and sexual symptom scores , operative time , blood loss , length of hospitalization , and adverse events . RESULTS : Thirty-eight women had anterior colporrhaphy , and 37 had polypropylene mesh repair . One patient allocated to mesh repair withdrew from the study before surgery . Clinical and demographic data did not differ significantly between the two treatment groups . One year after surgery , optimal and satisfactory anterior vaginal support were obtained in 21 of 38 ( 55 % ) of the colporrhaphy group and 33 of 38 ( 87 % ) of the mesh group ( P=.005 ) . Patients in both groups reported less bother after surgery in both prolapse and urinary symptoms . The rates of de novo dyspareunia were 4 of 26 ( 16 % ) and 2 of 23 ( 9 % ) in the colporrhaphy and mesh groups , respectively . Two of 37 ( 5 % ) patients had vaginal mesh extrusion . Nine anterior colporrhaphy patients would have to have recurrent anterior vaginal prolapse to prevent one vaginal mesh extrusion . Neither serious adverse events nor deaths occurred in either group . CONCLUSION : Anterior vaginal prolapse repair with polypropylene mesh reinforcement offers lower anatomic recurrence than anterior colporrhaphy at one year . However , quality of life and sexual symptoms scores improved in both groups . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00535301 LEVEL OF EVIDENCE : In a multicentre r and omised , unblinded patient preference pilot trial to assess the feasibility of a definitive r and omised trial comparing colposuspension with tension‐free vaginal tape ( TVT ) plus anterior repair in women with incontinence and prolapse , we found that 31 of 56 eligible women agreed to participate ( 55 % ) . Recruitment was more successful face to face ( 87 % ) than by letter ( 16 % ) . Only four of our women agreed to be r and omised , 21 ( 68 % ) chose anterior repair + TVT and six ( 19 % ) chose colposuspension . This study demonstrates the importance of pilot work for complex trials to identify issues likely to adversely affect recruitment Research on surgical interventions is associated with several method ological and practical challenges of which few , if any , apply only to surgery . However , surgical evaluation is especially dem and ing because many of these challenges coincide . In this report , the second of three on surgical innovation and evaluation , we discuss obstacles related to the study design of r and omised controlled trials and non-r and omised studies assessing surgical interventions . We also describe the issues related to the nature of surgical procedures -for example , their complexity , surgeon-related factors , and the range of outcomes . Although difficult , surgical evaluation is achievable and necessary . Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential |
761 | 27,683,350 | Of these markers , only the use of FOBT in screening for CRC has been shown to reduce mortality from cancer .
This lack of sensitivity and specificity when combined with the low prevalence of cancers in the general population means that most biomarkers , if used alone , have a low positive predictive value in screening asymptomatic population s. Indeed , it is the low prevalence of cancer in the general population that prohibits most biomarkers from being used alone , in screening for cancer ( 4,5 ) . | BACKGROUND Screening for premalignant lesions or early invasive disease has the potential to reduce mortality from cancer .
Potential screening tests for malignancy include measurement of (bio)markers .
Because of their ease of measurement , several biomarkers have been evaluated or are currently undergoing evaluation as screening tests for early malignancy .
CONCLUSION Although biomarkers have many attractions as screening tests , inadequate sensitivity and specificity , when combined with the low prevalence of cancer in asymptomatic subjects , limit their value for the early detection of malignancy .
Screening has been defined as the systematic application of a test to identify subjects at sufficient risk of a specific disorder to benefit from further investigation or direct preventive action , among persons who have not sought medical attention on account of symptoms of that disorder ( 1 ) .
Currently , only a small number of screening tests have been shown to reduce mortality from cancer .
These include mammography in screening for breast cancer ( especially in women > 50 years of age ) , the Papanicalaou ( PAP ) test in screening for cervical cancer and fecal occult blood testing ( FOBT ) in screening for colorectal cancer ( CRC ) ( for review , see refs .
2,3 ) .
Compared to procedures such as radiology , cytology and endoscopy , the use of biomarkers as cancer screening tests have several advantages ( 4 ) .
This in turn should lead to high compliance rates .
For many biomarkers , automated assays are available , thus allowing the processing of large numbers of sample s in a relatively short period of time .
Tests for biomarkers provide quantitative results with objective endpoints .
In practice however , lack of sensitivity for early invasive disease or premalignant lesions and lack of specificity for malignancy limit the use of existing biomarkers in screening asymptomatic subjects for early malignancy ( 4,5 ) .
These markers include the use of vanillym and elic acid ( VMA ) and homovanillic acid ( HVA ) in screening for neuroblastoma in newborns , AFP in screening for hepatocellular cancer in high-risk subjects , CA 125 in combination with transvaginal ultrasound ( TVU ) in screening for ovarian cancer , PSA in screening for prostate cancer and fecal occult blood testing ( FOBT ) in screening for CRC .
The aim of this article is to critically review the role of these biomarkers in screening normal-risk asymptomatic subjects for early cancer . | Objectives : To investigate the effectiveness of screening for liver cancer in reducing mortality from the disease in a high-risk population in China . Setting : A r and omised controlled trial was carried out among men aged 30 - 69 who were chronic carriers of hepatitis-B virus ( HBsAg positive ) during the period 1989 - 1995 in Qidong county , Jiangsu Province , China . Methods : 5581 HBsAg carriers were identified by population screening and r and omly assigned to a screening group ( group A , 3712 men ) , and controls ( group B , 1869 men ) . Screening was planned to be six monthly alpha-fetoprotein ( AFP ) assays , with follow-up of subjects having an abnormal ( ≥20 μg/l ) test . All subjects were followed up for liver cancer and /or death until 31 December 1995 . Results : The overall sensitivity and specificity of the programme was 55.3 % and 86.5 % , respectively ; in subjects who complied with all scheduled screening tests , the values were 80.0 % and 80.9 % . Three hundred and seventy-four primary liver cancer ( PLC ) cases were diagnosed . The percentage of cases in stage I was significantly higher in group A ( 29.6 % ) than in group B ( 6.0 % ) . The one- , three- , and five-year relative survival rates were 23.7 % , 7.0 % , and 4.0 % in group A , and 9.7 % , 4.0 % , and 4.1 % in group B respectively , with no difference in five-year survival between the groups . The mortality rate in the screened group ( 1138 per 100,000 person-years ) was not significantly different from that in the controls ( 1114 per 100,000 ) . A Poisson regression model showed that the probability of death ( rate ratio ) in the screening group was 0.83 ( 95 % CI 0.68 - 1.03 ) relative to the control group . Conclusions : Screening with AFP result ed in earlier diagnosis of liver cancer , but the gain in lead time did not result in any overall reduction in mortality , because therapy for the patients found by screening was ineffective . Further studies using improved methods of screening , diagnosis and treatment are indicated BACKGROUND The European R and omized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen ( PSA ) testing on death rates from prostate cancer . METHODS We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study . The men were r and omly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening . The predefined core age group for this study included 162,243 men between the ages of 55 and 69 years . The primary outcome was the rate of death from prostate cancer . Mortality follow-up was identical for the two study groups and ended on December 31 , 2006 . RESULTS In the screening group , 82 % of men accepted at least one offer of screening . During a median follow-up of 9 years , the cumulative incidence of prostate cancer was 8.2 % in the screening group and 4.8 % in the control group . The rate ratio for death from prostate cancer in the screening group , as compared with the control group , was 0.80 ( 95 % confidence interval [ CI ] , 0.65 to 0.98 ; adjusted P=0.04 ) . The absolute risk difference was 0.71 death per 1000 men . This means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer . The analysis of men who were actually screened during the first round ( excluding subjects with noncompliance ) provided a rate ratio for death from prostate cancer of 0.73 ( 95 % CI , 0.56 to 0.90 ) . CONCLUSIONS PSA-based screening reduced the rate of death from prostate cancer by 20 % but was associated with a high risk of overdiagnosis . ( Current Controlled Trials number , IS RCT N49127736 . BACKGROUND The effect of screening with prostate-specific-antigen ( PSA ) testing and digital rectal examination on the rate of death from prostate cancer is unknown . This is the first report from the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial on prostate-cancer mortality . METHODS From 1993 through 2001 , we r and omly assigned 76,693 men at 10 U.S. study centers to receive either annual screening ( 38,343 subjects ) or usual care as the control ( 38,350 subjects ) . Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years . The subjects and health care providers received the results and decided on the type of follow-up evaluation . Usual care sometimes included screening , as some organizations have recommended . The numbers of all cancers and deaths and causes of death were ascertained . RESULTS In the screening group , rates of compliance were 85 % for PSA testing and 86 % for digital rectal examination . Rates of screening in the control group increased from 40 % in the first year to 52 % in the sixth year for PSA testing and ranged from 41 to 46 % for digital rectal examination . After 7 years of follow-up , the incidence of prostate cancer per 10,000 person-years was 116 ( 2820 cancers ) in the screening group and 95 ( 2322 cancers ) in the control group ( rate ratio , 1.22 ; 95 % confidence interval [ CI ] , 1.16 to 1.29 ) . The incidence of death per 10,000 person-years was 2.0 ( 50 deaths ) in the screening group and 1.7 ( 44 deaths ) in the control group ( rate ratio , 1.13 ; 95 % CI , 0.75 to 1.70 ) . The data at 10 years were 67 % complete and consistent with these overall findings . CONCLUSIONS After 7 to 10 years of follow-up , the rate of death from prostate cancer was very low and did not differ significantly between the two study groups . ( Clinical Trials.gov number , NCT00002540 . PURPOSE This clinical trial is aim ed at evaluating the impact of prostate cancer screening on cancer-specific mortality . SUBJECTS AND METHODS Forty-six thous and four hundred and eighty-six ( 46,486 ) men aged 45 - 80 years registered in the electoral roll of the Quebec city area were r and omized in 1988 between screening and no screening . Screening included measurement of serum prostatic specific antigen ( PSA ) using 3.0 ng/ml as upper limit of normal and digital rectal examination ( DRE ) at first visit . At follow-up visits , serum PSA only was used . RESULTS Seventy-four ( 74 ) deaths from prostate cancer occurred in the 14,231 unscreened controls while 10 deaths were observed in the screened group of 7,348 men during the first 11 years following r and omization . Median follow-up of screened men was 7.93 years . A Cox proportional hazards model of the age at death from prostate cancer shows a 62 % reduction ( P < 0.002 , Fisher 's exact test ) of cause-specific mortality in the screened men ( P = 0.005 ) . These results are in agreement with the continuous decrease of prostate cancer mortality observed in North America Purpose Screening for hepatocellular carcinoma ( HCC ) has been conducted for over 20 years , but there is no conclusive evidence that screening may reduce HCC mortality . The aim of this study was to assess the effect of screening on HCC mortality in people at increased risk . Methods This study included 18,816 people , aged 35–59 years with hepatitis B virus infection or a history of chronic hepatitis in urban Shanghai , China . Participants were r and omly allocated to a screening ( 9,373 ) or control ( 9,443 ) group . Controls received no screening and continued to use health-care facilities . Screening group participants were invited to have an AFP test and ultrasonography examination every 6 months . Screening was stopped in December 1997 ; by that time screening group participants had been offered five to ten times . All participants were followed up until December 1998 . The primary outcome measure was HCC mortality . Results The screened group completed 58.2 percent of the screening offered . When the screening group was compared to the control group , the number of HCC was 86 versus 67 ; sub clinical HCC being 52 ( 60.5 % ) versus 0 ; small HCC 39 ( 45.3 % ) versus 0 ; resection achieved 40 ( 46.5 % ) versus 5 ( 7.5 % ) ; 1- , 3,- , and 5-year survival rate 65.9 % , 52.6 % , 46.4 % versus 31.2 % , 7.2 % , 0 , respectively . Thirty-two people died from HCC in the screened group versus 54 in the control group , and the HCC mortality rate was significantly lower in the screened group than in controls , being 83.2/100,000 and 131.5/100,000 , respectively , with a mortality rate ratio of 0.63 ( 95%CI 0.41–0.98 ) . Conclusions Our finding indicated that biannual screening reduced HCC mortality by 37 % Stored sample s from women in the Stockholm screening study were reassayed for CA125II ( Centocor , Malvern , PA ) and OVX1 . The postmenopausal women older than age 50 without ovarian cancer were r and omly split into a training set to develop a screening test based on longitudinal marker levels and a second set to vali date the test . The CA125II data from each woman is summarized by the slope and intercept from a linear regression of log(CAl25II ) on time since first sample . The slope versus the intercept for the training set and the ovarian cancer cases formed a bivariate scatter plot . A curve was drawn on the scatter plot that separated most of the women with ovarian cancer from all other women ; it delineated a screening test . The specificity of this test was examined on the validation set with a specificity of 99.8 % . Bayes ' theorem was used to calculate the risk of ovarian cancer ( ROC ) based on the intercept , slope , and assay variability . It is important to account for assay variability because it can produce large slopes over short periods of time . The maximum risk , which identified 83 % ( 5 of 6 ) of the ovarian cancers detected within a year of last assay , was applied as a test to the training set and confirmed a high specificity of 99.7 % . With this specificity and sensitivity , the ROC algorithm using the CA125II assay has an estimated positive predictive value of 16 % , substantially greater than the positive predictive value based on a single assay . Further study is planned to confirm the sensitivity of this approach . Cancer 1995 ; 76:2004‐10 New stool tests may be promising tools for future colorectal cancer ( CRC ) screening . The aim of this review was to summarize current evidence of performance characteristics and practicalness in a population ‐based screening setting of recently developed stool tests . The MEDLINE data base was search ed for relevant articles published until July 2004 . Studies were included if they comprised more than 10 cases and more than 10 controls . Details on study population , performance characteristics and stool collection procedure were taken into account . Overall , 29 studies , mostly retrospective , were included , investigating 17 different stool markers or marker combinations . Underlying study population s were very heterogeneous and mostly very small . Half of the studies reported sensitivity for adenomas in addition to sensitivity for CRC , and fewer than half reported sensitivity by tumor stage or location . Performance characteristics of stool tests varied to a large extent . For most DNA‐based markers , specificity was about 95 % or higher , but sensitivity was mostly low even for invasive CRC . More studies with larger sample sizes were done for protein‐based markers , which typically had lower specificity . In most studies , stool sample s were frozen within a rather short time period after defecation . While promising performance characteristics have been reported for some tests , more pervasive evidence from larger , prospect ively design ed studies , which also consider aspects of practicalness , e.g. , the possibility of mailing the sample s , is needed . © 2005 Wiley‐Liss , PURPOSE To evaluate prevalence screening in the first prospect i ve trial of a new ovarian cancer screening ( OCS ) strategy ( risk of ovarian cancer or ROC algorithm ) on the basis of age and CA125 profile . PATIENTS AND METHODS Postmenopausal women , > or = 50 years were r and omly assigned to a control group or screen group . Screening involved serum CA125 , interpreted using the ROC algorithm . Participants with normal results returned to annual screening ; those with intermediate results had repeat CA125 testing ; and those with elevated values underwent transvaginal ultrasound ( TVS ) . Women with abnormal or persistently equivocal TVS were referred for a gynecologic opinion . RESULTS Thirteen thous and five hundred eighty-two women were recruited . Of 6,682 women r and omly assigned to screening , 6,532 women underwent the first screen . After the initial CA125 , 5,213 women were classified as normal risk , 91 women elevated , and 1,228 women intermediate . On repeat CA125 testing of the latter , a further 53 women were classified as elevated risk . All 144 women with elevated risk had TVS . Sixteen women underwent surgery . Eleven women had benign pathology ; one woman had ovarian recurrence of breast cancer ; one woman had borderline ; and three women had primary invasive epithelial ovarian cancer ( EOC ) . The specificity and positive predictive value ( PPV ) for primary invasive EOC were 99.8 % ( 95 % CI , 99.7 to 99.9 ) and 19 % ( 95 % CI , 4.1 to 45.6 ) , respectively . CONCLUSION An OCS strategy using the ROC algorithm is feasible and can achieve high specificity and PPV in postmenopausal women . It is being used in the United Kingdom Collaborative Trial of Ovarian Cancer Screening and in the United States in both the Cancer Genetics Network and the Gynecology Oncology Group trials of high-risk women PURPOSE Previous studies of CA-125 levels from screening trials for ovarian cancer have indicated that serial CA-125 levels may identify cases better than a fixed CA-125 cutoff . We conducted a study to assess the screening performance of the risk of ovarian cancer calculation based on serial CA-125 levels from prospect ively collected serum sample s compared with a fixed CA-125 cutoff . PATIENTS AND METHODS The calculation was applied to data from a prospect i ve trial of screening for ovarian cancer involving 22,000 postmenopausal women older than 45 years . The analysis was performed using 33,621 CA-125 results from 9,233 women for whom two or more serial sample s were available . All serum sample s from the patients with ovarian cancer were obtained before clinical detection . Sensitivity and specificity levels for pre clinical detection of index cancers were calculated for various cutoffs for the risk and a single CA-125 measurement , and receiver operator curves were constructed . RESULTS The risk calculation significantly improved the area under the curve from 84 % to 93 % compared with a fixed cutoff for CA-125 ( P = .01 ) . For a target specificity of 98 % , the risk achieved a sensitivity of 86 % for pre clinical detection of ovarian cancer , whereas CA-125 achieved a sensitivity of 62 % . The estimates of performance are unbiased , because the risk calculation was derived independent of the data from this trial . CONCLUSION These results provide the first evidence that pre clinical detection of ovarian cancer using serial CA-125 levels interpreted with the risk calculation significantly improves screening performance compared with a fixed cutoff for CA-125 . The results justify the incorporation of the risk calculation in a prospect i ve , r and omized , controlled trial BACKGROUND The 46,193 men aged 45 to 80 years registered in the electoral roll of Quebec City and its Metropolitan area were r and omized in November 1988 between screening and no screening in a study aim ed of assessing the impact of prostate cancer screening on cause-specific death . METHODS At first visit , screening included measurement of serum prostatic specific antigen ( PSA ) using 3.0 ng/ml as upper limit of normal and a digital rectal examination ( DRE ) . Transrectal echography of the prostate ( TRUS ) was performed only if PSA and /or DRE was abnormal and biopsy was then done , only if PSA was above the predicted PSA value . At follow-up visits , PSA alone was used as prescreening . RESULTS 137 deaths due to prostate cancer occurred between 1989 and 1996 , inclusively , in the 38,056 unscreened men while only 5 deaths were observed among the 8,137 screened individuals . The prostate cancer death rates during the eight-year period were 48.7 and 15 per 100,000 man-years in the unscreened and screened groups , respectively , for a 3.25 odds ratio in favor of screening and early treatment ( P < 0.01 ) . CONCLUSIONS If PSA screening is started at the age of 50 years ( or 45 years in the higher risk population ) , annual or biannual PSA alone is highly efficient to identify the men who are at high risk of having prostate cancer . Coupled with treatment of localized disease , this approach demonstrates , for the first time , that early diagnosis and treatment permits a dramatic decrease in deaths from prostate cancer BACKGROUND The value of screening for ovarian cancer is uncertain . We did a pilot r and omised trial to assess multimodal screening with sequential CA 125 antigen and ultrasonography . METHODS Postmenopausal women aged 45 years or older were r and omised to a control group ( n=10,977 ) or screened group ( n=10,958 ) . Women r and omised to screening were offered three annual screens that involved measurement of serum CA 125 , pelvic ultrasonography if CA 125 was 30 U/mL or more , and referral for gynaecological opinion if ovarian volume was 8.8 mL or more on ultrasonography . All women were followed up to see whether they developed invasive epithelial cancers of the ovary or fallopian tube ( index cancers ) . FINDINGS Of 468 women in the screened group with a raised CA 125 , 29 were referred for a gynaecological opinion ; screening detected an index cancer in six and 23 had false-positive screening results . The positive predictive value was 20.7 % . During 7-year follow-up , ten further women with index cancers were identified in the screened group and 20 in the control group . Median survival of women with index cancers in the screened group was 72.9 months and in the control group was 41.8 months ( p=0.0112 ) . The number of deaths from an index cancer did not differ significantly between the control and screened groups ( 18 of 10,977 vs nine of 10,958 , relative risk 2.0 [ 95 % CI 0.78 - 5.13 ] ) . INTERPRETATION These results show that a multimodal approach to ovarian cancer screening in a r and omised trial is feasible and justify a larger r and omised trial to see whether screening affects mortality BACKGROUND Ovarian cancer has a high case-fatality ratio , with most women not diagnosed until the disease is in its advanced stages . The United Kingdom Collaborative Trial of Ovarian Cancer Screening ( UKCTOCS ) is a r and omised controlled trial design ed to assess the effect of screening on mortality . This report summarises the outcome of the prevalence ( initial ) screen in UKCTOCS . METHODS Between 2001 and 2005 , a total of 202 638 post-menopausal women aged 50 - 74 years were r and omly assigned to no treatment ( control ; n=101 359 ) ; annual CA125 screening ( interpreted using a risk of ovarian cancer algorithm ) with transvaginal ultrasound scan as a second-line test ( multimodal screening [ MMS ] ; n=50 640 ) ; or annual screening with transvaginal ultrasound ( USS ; n=50 639 ) alone in a 2:1:1 ratio using a computer-generated r and om number algorithm . All women provided a blood sample at recruitment . Women r and omised to the MMS group had their blood tested for CA125 and those r and omised to the USS group were sent an appointment to attend for a transvaginal scan . Women with abnormal screens had repeat tests . Women with persistent abnormality on repeat screens underwent clinical evaluation and , where appropriate , surgery . This trial is registered as IS RCT N22488978 and with Clinical Trials.gov , number NCT00058032 . FINDINGS In the prevalence screen , 50 078 ( 98.9 % ) women underwent MMS , and 48 230 ( 95.2 % ) underwent USS . The main reasons for withdrawal were death ( two MMS , 28 USS ) , non-ovarian cancer or other disease ( none MMS , 66 USS ) , removal of ovaries ( five MMS , 29 USS ) , relocation ( none MMS , 39 USS ) , failure to attend three appointments for the screen ( 72 MMS , 757 USS ) , and participant changing their mind ( 483 MMS , 1490 USS ) . Overall , 4355 of 50 078 ( 8.7 % ) women in the MMS group and 5779 of 48 230 ( 12.0 % ) women in the USS group required a repeat test , and 167 ( 0.3 % ) women in the MMS group and 1894 ( 3.9 % ) women in the USS group required clinical evaluation . 97 of 50 078 ( 0.2 % ) women from the MMS group and 845 of 48 230 ( 1.8 % ) from the USS group underwent surgery . 42 ( MMS ) and 45 ( USS ) primary ovarian and tubal cancers were detected , including 28 borderline tumours ( eight MMS , 20 USS ) . 28 ( 16 MMS , 12 USS ) of 58 ( 48.3 % ; 95 % CI 35.0 - 61.8 ) of the invasive cancers were stage I/II , with no difference ( p=0.396 ) in stage distribution between the groups . A further 13 ( five MMS , eight USS ) women developed primary ovarian cancer during the year after the screen . The sensitivity , specificity , and positive-predictive values for all primary ovarian and tubal cancers were 89.4 % , 99.8 % , and 43.3 % for MMS , and 84.9 % , 98.2 % , and 5.3 % for USS , respectively . For primary invasive epithelial ovarian and tubal cancers , the sensitivity , specificity , and positive-predictive values were 89.5 % , 99.8 % , and 35.1 % for MMS , and 75.0 % , 98.2 % , and 2.8 % for USS , respectively . There was a significant difference in specificity ( p<0.0001 ) but not sensitivity between the two screening groups for both primary ovarian and tubal cancers as well as primary epithelial invasive ovarian and tubal cancers . INTERPRETATION The sensitivity of the MMS and USS screening strategies is encouraging . Specificity was higher in the MMS than in the USS group , result ing in lower rates of repeat testing and surgery . This in part reflects the high prevalence of benign adnexal abnormalities and the more frequent detection of borderline tumours in the USS group . The prevalence screen has established that the screening strategies are feasible . The results of ongoing screening are awaited so that the effect of screening on mortality can be determined BACKGROUND Although fecal occult-blood testing is the only available noninvasive screening method that reduces the risk of death from colorectal cancer , it has limited sensitivity . We compared an approach that identifies abnormal DNA in stool sample s with the Hemoccult II fecal occult-blood test in average-risk , asymptomatic persons 50 years of age or older . METHODS Eligible subjects su bmi tted one stool specimen for DNA analysis , underwent st and ard Hemoccult II testing , and then underwent colonoscopy . Of 5486 subjects enrolled , 4404 completed all aspects of the study . A subgroup of 2507 subjects was analyzed , including all those with a diagnosis of invasive adenocarcinoma or advanced adenoma plus r and omly chosen subjects with no polyps or minor polyps . The fecal DNA panel consisted of 21 mutations . RESULTS The fecal DNA panel detected 16 of 31 invasive cancers , whereas Hemoccult II identified 4 of 31 ( 51.6 percent vs. 12.9 percent , P=0.003 ) . The DNA panel detected 29 of 71 invasive cancers plus adenomas with high- grade dysplasia , whereas Hemoccult II identified 10 of 71 ( 40.8 percent vs. 14.1 percent , P<0.001 ) . Among 418 subjects with advanced neoplasia ( defined as a tubular adenoma at least 1 cm in diameter , a polyp with a villous histologic appearance , a polyp with high- grade dysplasia , or cancer ) , the DNA panel was positive in 76 ( 18.2 percent ) , whereas Hemoccult II was positive in 45 ( 10.8 percent ) . Specificity in subjects with negative findings on colonoscopy was 94.4 percent for the fecal DNA panel and 95.2 percent for Hemoccult II . CONCLUSIONS Although the majority of neoplastic lesions identified by colonoscopy were not detected by either noninvasive test , the multitarget analysis of fecal DNA detected a greater proportion of important colorectal neoplasia than did Hemoccult II without compromising specificity BACKGROUND One type of fecal occult blood test ( FOBT ) , the unrehydrated guaiac fecal occult blood test ( GT ) , is recommended by the United States Preventive Services Task Force and the Institute of Medicine for use in screening programs , but it has relatively low sensitivity as a single test for detecting advanced colonic neoplasms ( cancer and adenomatous polyps > or = 1 cm in diameter ) . Thus , improving the sensitivity of FOBT should make colon cancer screening programs that use these tests more effective . METHODS We assessed prospect ively the performance characteristics of two newer FOBTs in 5841 subjects at average risk for colorectal cancer in a large group-model managed care organization . The tests evaluated included a sensitive GT , a fecal immunochemical test ( FIT ) , and the combination of both tests . Patients with positive and negative test results were advised to have colonoscopy and sigmoidoscopy , respectively . Sensitivity and specificity for detecting advanced neoplasms in the left colon within 2 years after the FOBT screening were evaluated for the two tests administered separately and in combination . RESULTS A total of 139 patients were diagnosed with advanced colorectal neoplasms ( n = 14 cancers , n = 128 adenomas ) within the 2 years following their initial FOBT screening . Sensitivity for detecting cancer was 81.8 % ( 95 % confidence interval [ CI ] = 47.8 % to 96.8 % ) for the FIT alone and 64.3 % ( 95 % CI = 35.6 % to 86.0 % ) for the sensitive GT and the combination test . Sensitivity for detecting advanced colorectal adenomas was 41.3 % ( 95 % CI = 32.7 % to 50.4 % ) for the sensitive GT , 29.5 % ( 95 % CI = 21.4 % to 38.9 % ) for the FIT , and 22.8 % ( 95 % CI = 16.1 % to 31.3 % ) for the combination test . Specificity for detecting cancer and adenomas was 98.1 % ( 95 % CI = 97.7 % to 98.4 % ) and 98.4 % ( 95 % CI = 98.0 % to 98.7 % ) , respectively , for the combination test ; 96.9 % ( 95 % CI = 96.4 % to 97.4 % ) and 97.3 % ( 95 % CI = 96.8 % to 97.7 % ) , respectively , for the FIT ; and 90.1 % ( 95 % CI = 89.3 % to 90.8 % ) and 90.6 % ( 95 % CI = 89.8 % to 91.4 % ) , respectively , for the sensitive GT . CONCLUSIONS The FIT has high sensitivity and specificity for detecting left-sided colorectal cancer , and it may be a useful replacement for the GT Two large‐scale r and omized screening trials , the Prostate , Lung , Colorectal and Ovary ( PLCO ) cancer trial in the USA and the European R and omized Screening for Prostate Cancer ( ERSPC ) trial in Europe are currently under way , aim ed at assessing whether screening reduces prostate cancer mortality . Up to the end of 1998 , 102,691 men have been r and omized to the intervention arm and 115,322 to the control arm ( which represents 83 % of the target sample size ) from 7 European countries and 10 screening centers in the USA . The principal screening method at all centers is determination of serum prostate‐specific antigen ( PSA ) . The PLCO trial and some European centers use also digital rectal examination ( DRE ) as an ancillary screening test . In the core age group ( 55–69 years ) , 3,362 of 32,486 men screened ( 10 % ) had a serum PSA concentration of 4 ng/ml or greater , which is 1 cut‐off for biopsy ( performed in 84 % ) . An additional 6 % was referred for further assessment based on other criteria , with much less efficiency . Differences in PSA by country are largely attributable to the age structure of the study population . The mean age‐specific PSA levels are lower in the PLCO trial ( 1.64 ng/ml [ in the age group 55–59 years ] , 1.80 [ 60–64 years ] and 2.18 [ 65–69 years ) than in the ERSPC trial ( 1.28–1.71 [ 55–59 ] , 1.75–2.87 [ 60–64 ] and 2.48–3.06 [ 65–69 years ] ) . Detection rates at the first screen in the ERSPC trial range from 11 to 42/1,000 men screened and reflect underlying differences in incidence rates and screening procedures . In centers with consent to r and omization design , adherence in the screening arm is 91 % , but less than half of the men in the target population are enrolled in the trial . In population ‐based centers in which men were r and omized prior to consent , all eligible subjects are enrolled , but only about two‐thirds of the men in the intervention arm undergo screening . Considerable progress has been made in both trials . Enrollment will be completed in 2001 . A substantial number of early prostate cancers have been detected . The differences between countries seem to reflect both underlying prostate cancer incidence and screening policy . The trials have the power to show definitive results in 2005–2008 . © 2002 Wiley‐Liss , OBJECTIVE To test the feasibility of a population -based prostate cancer screening programme in general practice and explore the outcome after a 15-year follow-up period . METHODS From the total population of men aged 50 - 69 years in Norrköping ( n = 9026 ) every sixth man ( n = 1494 ) was r and omly selected to be screened for prostate cancer every third year over a 12-year period . The remaining 7532 men were treated as controls . In 1987 and 1990 only digital rectal examination ( DRE ) was performed , in 1993 and 1996 DRE was combined with a test for Prostate-Specific Antigen ( PSA ) . TNM categories , grade of malignancy , management and cause of death were recorded in the South-East Region Prostate Cancer Register . RESULTS There were 85 ( 5.7 % ) cancers detected in the screened group ( SG ) , 42 of these in the interval between screenings , and 292 ( 3.8 % ) in the unscreened group ( UG ) . In the SG 48 ( 56.5 % ) of the tumours and in the UG 78 ( 26.7 % ) were localised at diagnosis ( p < 0.001 ) . In the SG 21 ( 25 % ) and in the UG 41 ( 14 % ) received curative treatment . There was no significant difference in total or prostate cancer-specific survival between the groups . CONCLUSIONS Although PSA had not been introduced in the clinical practice at the start of the study , we were still able to show that it is possible to perform a long-term population -based r and omised controlled study with st and ardised management and that screening in general practice is an efficient way of detecting prostate cancer whilst it is localised . Complete data on stage , treatment and mortality for both groups was obtained from a vali date d cancer register , which is a fundamental prerequisite when assessing screening programmes Screening for prostate cancer and subsequent treatment is of unknown benefit but carries known treatment related morbidity and mortality risks . The recent enthusiasm for screening in the United States contrasts sharply with the more cautious attitudes of the European and Canadian medical communities . Current data from screening series without r and omization and controls are inadequate to determine screening benefit . The prostate , lung , colorectal and ovarian cancer ( r and omized , controlled ) screening trial of the National Cancer Institute , to include 74,000 men ( and 74,000 women ) 60 to 74 years old , has a design power of 90 % to determine a 20 % reduction of prostate cancer mortality from a baseline and 3 subsequent annual screens using prostate specific antigen and digital rectal examination . R and omization of participants into this trial began on November 16 , 1993 . Ten screening centers nationwide , a coordinating center , a laboratory and a biorepository are participating under contract OBJECTIVE To assess the validity and cost of a screening test for primary liver cancer using combined serum alpha fetoprotein testing and ultrasonography . SETTING An urban community in Shanghai , China . METHODS 9373 subjects aged 35 to 59 with positive hepatitis B surface antigen ( HBsAg ) or chronic hepatitis were studied . Outcome measures were detection rate , false positive rate , and positive predictive value , the cost for each primary liver cancer detected , and the average cost of detecting each additional primary liver cancer by the combined method . The number of small primary liver cancers detected was used for the economic evaluation . RESULTS 20,294 screening examinations were carried out . Primary liver cancer was detected in 51 subjects , 36 of whom had small primary liver cancer . When alpha fetoprotein and ultrasonography were used in parallel the detection rate , false positive rate , and positive predictive value were 92 % , 7.5 % , and 3.0 % , respectively ; the cost for each primary liver cancer detected was 30,206 RMB ( Chinese currency , $ 3639 ) . When ultrasonography was used alone the detection rate , false positive rate , and positive predictive value were 84 % , 2.9 % , and 6.6 % , respectively ; the cost for each primary liver cancer detected was 16,451 RMB ( $ 1982 ) . When the alpha fetoprotein test was used alone the detection rate , false positive rate , and positive predictive value were 69 % , 5.0 % , and 3.3 % , respectively ; the cost for each primary liver cancer detected was 25,139 RMB ( $ 3029 ) . CONCLUSION The combination of both screening methods results in a relatively small increase in detection but a considerably higher false positive rate , increasing the costs . The combined test may be the best choice for primary liver cancer screening in developed areas of China , but otherwise , ultrasonography alone is the method of choice CA125 is currently the most widely used tumor marker for ovarian epithelial cancer . The aim of this article is to provide guidelines for the routine clinical use of CA125 in patients with ovarian cancer . Due to lack of sensitivity for stage I disease and lack of specificity , CA125 is of little value in the detection of early ovarian cancer . At present , therefore , CA125 , either alone or in combination with other modalities , can not be recommended for screening for ovarian cancer in asymptomatic women outside the context of a r and omized controlled trial . Preoperative levels in postmenopausal women , however , may aid the differentiation of benign and malignant pelvic masses . Serial levels during chemotherapy for ovarian cancer are useful for assessing response to treatment . Although serial monitoring following initial chemotherapy can lead to the early detection of recurrent disease , the clinical value of this lead-time is unclear . CA125 is the ovarian cancer marker against which new markers for this malignancy should be judged Context Because the colonic mucosa constantly sheds cells , testing stool for cancer-related genes could be better for colorectal cancer screening than testing for occult bleeding , which is intermittent . Content A total of 3764 healthy adults had screening colonoscopy , fecal occult blood testing with Hemoccult and HemoccultSensa , and both a first- and a second-generation stool DNA test ( SDT-1 and SDT-2 , respectively ) for a battery of cancer genes . The sensitivity of SDT-1 and HemoccultSensa was very similar for screen-relevant neoplasms ( 20 % and 21 % , respectively ) , whereas the sensitivity of SDT-2 was 40 % . Caution The authors could not measure the specificity of SDT-2 . Implication A second-generation stool test for cancer genes is substantially more sensitive than fecal occult blood testing . The Editors Colorectal cancer remains the second most common cause of death among the types of cancer ( 1 ) . Although screening reduces colorectal cancer mortality ( 26 ) , observed reductions have been modest ( 6 , 7 ) and more than one half of adults in the United States have not received screening ( 8) . More accurate , user-friendly , and widely distributable tools have the potential to improve screening effectiveness , acceptability , and access . Several molecular approaches to screening stool for colorectal cancer have been studied and review ed ( 9 , 10 ) , and stool DNA testing has been jointly endorsed by the American Cancer Society , the U.S. Multi-Society Task Force on Colorectal Cancer , and the American College of Radiology ( 11 ) . The advantages of stool DNA testing include noninvasiveness , absence of bowel preparation or dietary restrictions , and ease of access via mail courier . However , the reported accuracy of stool DNA tests for the detection of colorectal neoplasia varies . In clinical studies that used different assays and selected groups ( 1220 ) , sensitivities ranged from 62 % to 100 % for colorectal cancer and 27 % to 82 % for advanced adenomas , with specificities ranging from 82 % to 100 % . In the only reported multicenter study on asymptomatic average-risk patients ( 21 ) , a precommercial multitarget DNA assay ( SDT-1 , a prototype of PreGenPlus , EXACT Sciences , Marlborough , Massachusetts ) detected 52 % of cases of colorectal cancer , compared with 13 % by Hemoccult ( P = 0.003 ) , at specificities of 94.4 % and 95.2 % , respectively . The accuracy of stool DNA testing is influenced by both biological and technical factors . A panel of markers must be used to accommo date the molecular heterogeneity of colorectal neoplasia , and marker selection critically affects discrimination ( 9 ) . Unlike occult bleeding , which is intermittent ( 22 ) , DNA markers seem to be shed continuously by exfoliation ( 23 ) . Thus , the multiple stool sampling practice d with fecal occult blood tests may not be necessary with stool DNA tests . However , recovery of the minute quantities of human DNA and assay of tumor-specific DNA alterations from stool present technical challenges and require exquisite laboratory sensitivity to achieve optimal detection rates . Our primary aim was to compare the precommercial stool DNA test ( SDT-1 ) , which was studied by Imperiale and colleagues ( 21 ) , with widely used fecal occult blood tests for the detection of screen-relevant neoplasia , defined as curable-stage colorectal cancer ( no distant metastases ) , high- grade dysplasia , or adenomas larger than 1 cm . A secondary aim was to explore neoplasm detection by another stool DNA test 2 ( SDT-2 ) , which uses a more broadly informative marker panel . Methods Table 1 lists the genes used in our test panels and defines several key terms . Table 1 . Definitions Design We conducted this multicenter , prospect i ve , triple-blinded trial , targeting average-risk persons , from 2001 to 2007 . A group of national experts on colorectal cancer screening advised on study design , and institutional review boards at each site approved the study . Because we did not know the effect of diet and medications on DNA assays , patients were r and omly assigned at entry to group A ( restriction of red meat and therapeutic doses of nonsteroidal anti-inflammatory drugs for 3 days before and during stool collection s ) or group B ( no such restrictions ) . All patients were asked not to ingest vitamin C for the 3 days before and during stool collection s. For the companion test , we chose Hemoccult ( Beckman Coulter , Fullerton , California ) , the most widely used fecal occult blood test , which was used in the trials that established the benefit of screening for fecal occult blood ( 24 ) . As a second companion test , we chose the next-generation guaiac test HemoccultSensa ( Beckman Coulter ) . We compared fecal blood results from 3 stools per patient with stool DNA on 1 stool . Experienced technicians performed stool DNA and occult blood testing in separate central laboratories without knowledge of clinical findings or the results of other tests . All patients who completed stool collection s also had colonoscopy , which served as the criterion st and ard . We did not have access to data until after they had been analyzed by statisticians and released by a data monitoring board . Participants We recruited asymptomatic persons age 50 to 80 years who were at average risk for colorectal cancer from communities surrounding 22 participating academic and regional health care systems through direct mail and multimedia advertisements . The exclusion criteria were structural colorectal evaluation ( endoscopic or radiographic ) within 10 years ; fecal blood testing within 1 year ; overt rectal bleeding within 1 month ; previous colorectal resection ; aerodigestive cancer within 5 years ; inability to stop therapeutic doses of nonsteroidal anti-inflammatory drugs or anticoagulants ; coagulopathy ; contraindications to colonoscopy ; chemotherapy within 3 months ; high-risk conditions for colorectal cancer , such as familial adenomatous polyposis , the Lynch syndrome , or other cancer syndromes ; previous colorectal cancer or adenoma ; inflammatory bowel disease ; or more than 2 first-degree relatives with colorectal neoplasia . Study assistants at each site registered participants and r and omly assigned them by using a Web-based management system ; distributed fecal blood test cards , stool collection containers , and colonoscopy preparation material s ; and provided instructions . Stool Collection and Processing Patients collected 3 stools by using plastic buckets mounted to the toilet seat . Promptly after each individual collection , patients smeared stool onto both windows of their Hemoccult and HemoccultSensa cards and then express-shipped smeared cards and the whole stool ( sealed in a bucket in an insulated container cooled with ice packs ) to the Mayo Clinic in Rochester , Minnesota . We froze the first stool from each participant whole at 80 C on receipt and sent it in batches on dry ice to EXACT Sciences ( Marlborough , Massachusetts ) for DNA assay ; each of the subsequent 2 stools were archived in aliquots at 80 C. If the first stool weighed less than 30 g or was received more than 48 hours after defecation , it was rejected for DNA analysis and the second or third stool ( if it met inclusion criteria ) was sent for DNA assay . Stool Assays DNA Testing All assays were polymerase chain reactionbased and were run at EXACT Sciences . Stool DNA test 1 was performed as described in Imperiale and colleagues ' study ( 21 ) . The marker panel for SDT-1 included 21 tumor-specific point mutations ( 3 on the K-ras gene , 10 on the APC gene , and 8 on the p53 gene ) ; the microsatellite-instability marker BAT-26 ; and long DNA , a marker for delayed apoptosis , which is characteristic of exfoliated neoplastic colonocytes ( 12 ) . For SDT-2 , sequence-specific DNA markers were detected by acrylamide gel electrophoresis , as described by Whitney and colleagues ( 24 ) ; the panel consisted of 3 tumor-specific markers broadly informative for both colorectal cancer and adenomas ( 25 ) : K-ras mutations , scanning of APC mutator cluster regions , and methylation of the vimentin gene . We used methods described elsewhere to detect mutant K-ras ( 12 ) , APC scanning ( 25 ) , and vimentin gene methylation ( 20 ) assays . We defined any positive component marker result according to the manufacturer 's preestablished criteria as a positive test result . Occult Blood Testing The manufacturer that developed the Hemoccult and HemoccultSensa cards , without rehydration , trained technicians on-site at the Mayo Clinic . As recommended by the manufacturer , the technicians added the catalyst solution to cards stored at ambient temperature within 48 to 72 hours of collection . We defined a spreading ( enlarging ) blue color in 60 seconds in any window of the cards as a positive result and any other result as negative . Colonoscopy After cathartic preparation , experienced endoscopists performed colonoscopy in all patients . If the examination did not reach the cecum or inspected less than 90 % of the mucosa , the patient was disqualified . Endophotographs documented cecal intubation , and the size and location of all lesions were recorded . Costs not covered by third parties were reimbursed by study funding . Pathologic Examination Local pathologists examined all endoscopically or surgically sample d lesions . A gastrointestinal pathologist at the coordinating site reexamined all lesions to confirm diagnosis . Classification discrepancies of screen-relevant neoplasms were adjudicated by a second expert pathologist . We categorized patients with multiple neoplasms according to the most advanced lesion . For assay of markers in screen-relevant neoplasms , DNA was extracted from microdissected tissue . Statistical Analysis We calculated sample size to ensure adequate power to detect differences in sensitivity comparisons . We powered the study to ensure an adequate number of cases of curable-stage colorectal cancer and high- grade dysplasia and assumed their combined prevalence to be at least 1.5 % . A sample size of 2900 would yield an expected 43 curable-stage cancer or high- grade dysplasia cases , |
762 | 17,185,146 | This analysis suggests that fenoldopam reduces the need for renal replacement and mortality in patients with acute kidney injury . | BACKGROUND Acute kidney injury is common in critically ill patients .
Fenoldopam mesylate is a potent dopamine A-1 receptor agonist that increases blood flow to the renal cortex and outer medulla .
Because there is uncertainty about the benefits of fenoldopam in such a setting , we performed a systematic review of r and omized controlled trials of intensive care unit patients or those undergoing major surgery . | BACKGROUND AND OBJECTIVE Postoperative renal impairment is a recognized complication of infrarenal aortic cross-clamping . Our hypothesis was that the renal vasodilating and natriuretic effects of fenoldopam mesylate , a selective dopamine ( DA1 ) agonist , would preserve renal function in patients undergoing elective infrarenal aortic cross-clamping . METHODS A prospect i ve , r and omized , double blind controlled clinical trial was performed . Twenty-eight ASA II-III patients undergoing elective aortic surgery requiring infrarenal aortic cross-clamping were studied . According to r and om allocation , patients received either fenoldopam ( 0.1 microg kg(-1 ) min(-1 ) ) or placebo intravenously prior to surgical skin incision until release of the aortic clamp . Plasma creatinine , creatinine clearance , urinary output , fractional excretion of sodium , and free water clearance were measured : ( a ) prior to admission to hospital ; ( b ) during the period from insertion of the urinary catheter until application of the aortic cross-clamp ; ( c ) during the period of aortic cross-clamping ; ( d ) 0 - 4 h , and ( e ) 4 - 8 h after release of the clamp and on days 1 , 2 , 3 , and 5 postoperatively . RESULTS Fenoldopam ( 0.1 microg kg(-1)min(-1 ) ) administration was not associated with haemodynamic instability . On application of the aortic cross-clamp creatinine clearance decreased significantly in the placebo ( 83 + /- 20 to 42 + /- 29 mL min(-1 ) ( mean + /- SD ) ) ( P < 0.01 ) but not in the fenoldopam group , and this decrease persisted for at least 8 h after release of the cross-clamp ( 83 + /- 20 to 54 + /- 33 mL min(-1 ) ( mean + /- SD ) ) ( P < 0.05 ) . Plasma creatinine concentration increased significantly from baseline on the first postoperative day in the placebo group ( 87 + /- 12 to 103 + /- 28 micromolL(-1 ) ( mean + /- SD ) ) ( P < 0.01 ) but not in the fenoldopam group . CONCLUSIONS These findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect during and after infrarenal aortic cross-clamping Objective : Fenoldopam mesylate is a selective dopamine-1 agonist , with no effect on dopamine-2 and & agr;1 receptors , producing a selective renal vasodilation . This may favor the kidney oxygen supply/dem and ratio and prevent acute renal failure . The aim of the study was to investigate if fenoldopam can provide greater benefit than low-dose dopamine in early renal dysfunction of critically ill patients . Design : Prospect i ve , multiple-center , r and omized , controlled trial . Setting : University and city hospital intensive care units . Patients : One hundred adult critically ill patients with early renal dysfunction ( intensive care unit stay < 1 wk , hemodynamic stability , and urine output ≤0.5 mL/kg over a 6-hr period and /or serum creatinine concentration ≥1.5 mg/dL and ≤ 3.5 mg/dL ) . Interventions : Patients were r and omized to receive 2 & mgr;g/kg/min dopamine ( group D ) or 0.1 & mgr;g/kg/min fenoldopam mesylate ( group F ) . Drugs were administered as continuous infusion over a 4-day period . Measurements and Main Results : Systemic hemodynamic and renal function variables were recorded daily . The two groups were well matched at enrollment for illness severity and hemodynamic and renal dysfunction . No differences in heart rate or systolic , diastolic , or mean arterial pressure were observed between groups . Fenoldopam produced a more significant reduction in creatinine values compared with dopamine after 2 , 3 , and 4 days of infusion ( change from baseline at time 2 , −0.32 vs. −0.03 mg/dL , p = .047 ; at time 3 , −0.45 vs. −0.09 mg/dL , p = .047 ; and at time 4 , −.041 vs. −0.09 mg/dL , p = .02 , in groups F and D , respectively ) . The maximum decrease in creatinine compared with baseline was significantly greater in group F than group D ( −0.53 ± 0.47 vs. −0.34 ± 0.38 mg/dL , p = .027 ) . Moreover , 66 % of patients in group F had a creatinine decrease > 10 % of the baseline value at the end of infusion , compared with only 46 % in dopamine group ( chi-square = 4.06 , p = .04 ) . Total urinary output during drug infusion was not significantly different between groups . After 1 day , urinary output was lower in group F compared with group D ( p < .05 ) . Conclusions : In critically ill patients , a continuous infusion of fenoldopam at 0.1 & mgr;g/kg/min does not cause any clinical ly significant hemodynamic impairment and improves renal function compared with renal dose dopamine . In the setting of acute early renal dysfunction , before severe renal failure has occurred , the attempt to reverse renal hypoperfusion with fenoldopam is more effective than with low-dose dopamine To test the relative effects on serum creatinine ( CRE ) , blood urea nitrogen ( BUN ) , and urine output of small-dose dopamine and fenoldopam in patients undergoing liver transplantation , we r and omized 43 patients to 1 of 2 continuous infusions over 48 h , starting with anesthesia induction : fenoldopam , 0.1 & mgr;g · kg−1 · min−1 or dopamine , 2 & mgr;g · kg−1 · min−1 . We used predetermined hemodynamic and intravascular volume goals ( intrathoracic blood volume index 800–1000 mL/m2 , extravascular lung water index < 7 mL/kg ) to manage patients with an algorithm for use of mannitol and furosemide to maintain urine output > 1 mL · kg−1 · h−1 . At postoperative day 3 , the median CRE increase was 0.2 mg/dL ( interquartile range [ IQR ] −0.2–0.5 ) with fenoldopam and 0.5 mg/dL ( IQR 0.3–0.9 , P = 0.004 ) in the dopamine group . The BUN increase was median 2 mg/dL ( IQR −2–8 ) versus 8.5 mg/dL ( IQR 5–12 , P = 0.01 ) , respectively , with fenoldopam versus dopamine . Urine output was similar ; however , significantly fewer fenoldopam patients required furosemide compared with dopamine patients ( median 1 [ IQR 0–3 ] versus 3 [ IQR 2–4 ] , respectively , P = 0.003 ) . The hemodynamic effects of dopamine and fenoldopam were similar . Compared with dopamine , in the setting of liver transplantation , fenoldopam is associated with better CRE and BUN values Impairment of renal and splanchnic perfusion during and after cardiopulmonary bypass may be responsible for acute renal failure and endotoxin‐mediated systemic inflammation , respectively . We hypothesised that fenoldopam , a selective dopamine receptor agonist , would preserve renal function after cardiopulmonary bypass through its selective renal vasodilatory and natriuretic effects , and increase gastrointestinal mucosal perfusion by selective splanchnic vasodilation . We examined the effects of fenoldopam on haemodynamic parameters , creatinine clearance , fractional excretion of sodium , urine output , free water clearance and gastric mucosal pH in 31 patients undergoing elective coronary revascularisation . Patients were r and omly assigned to receive continuous infusions of fenoldopam 0.1 µg.kg−1.min−1 ( n = 16 ) or placebo ( n = 15 ) . Renal parameters were measured : during a 24‐h period before hospital admission , during cardiopulmonary bypass , from completion of cardiopulmonary bypass until 4 h later , from 4 to 8 h after cardiopulmonary bypass , and from 8 to 14 h after cardiopulmonary bypass . Gastric intramucosal pH was measured using a gastric tonometer before , during and after cardiopulmonary bypass . In the placebo group , but not the fenoldopam group , mean ( SD ) creatinine clearance decreased after separation from cardiopulmonary bypass , from 107 ( 36 ) to 71 ( 22 ) ml.min−1 ( p < 0.01 ) and from 107 ( 36 ) to 79 ( 26 ) ml.min−1 ( p < 0.01 ) for the 0–4 h and 4–8 h intervals after cardiopulmonary bypass , respectively . Changes in intramucosal pH were similar in both groups . The findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect in patients undergoing cardiopulmonary bypass Background : Inadequate splanchnic perfusion in septic shock is associated with increased morbidity and mortality . As result of splanchnic ischemia , mucosal permeability increases . Considering the implication of improved mucosal perfusion in terms of maintenance of mucosal barrier integrity , dopamine-1 receptor stimulation could be helpful in septic shock . The goal of the current study was to determine the effects of fenoldopam on systemic hemodynamic parameters and gastric mucosal perfusion in patients with septic shock . Furthermore , the authors tested the hypothesis that the addition of fenoldopam ( 0.1 & mgr;g · kg−1 · min−1 ) to a combination of norepinephrine and dobutamine ( 5 & mgr;g · kg−1 · min−1 ) may improve gastric mucosal perfusion in septic shock . Methods : Patients with septic shock were r and omized to a double-blind 2-h infusion of fenoldopam ( n = 20 ) or placebo ( n = 20 ) . Each group received dobutamine ( 5 & mgr;g · kg−1 · min−1 ) , and the dosage of norepinephrine was adjusted to achieve a mean arterial pressure between 70 and 80 mmHg . A laser-Doppler probe and tonometer were introduced into the gastric lumen . Results : A significant increase in gastric mucosal perfusion , detected by laser-Doppler flowmetry , was observed in the group treated with fenoldopam ( P < 0.05 ) . In addition , this increase in microcirculatory flow occurred despite the fact that systemic flow remained unchanged . Differences in gastroarterial partial pressure of carbon dioxide values were not statistically significant in the fenoldopam and placebo groups . Conclusions : The study showed that , for the same mean arterial pressure , short-term fenoldopam infusion increased gastric mucosal perfusion in patients with septic shock CONTEXT The development of contrast-induced nephropathy in patients undergoing invasive cardiac procedures is associated with a marked increase in cardiovascular morbidity and mortality . Fenoldopam mesylate , a specific agonist of the dopamine-1 receptor , preserves renal blood flow after iodinated contrast administration and has shown promise in ameliorating contrast nephropathy in previous observational and small r and omized trials . OBJECTIVE To examine the efficacy of fenoldopam mesylate in preventing contrast nephropathy after invasive cardiovascular procedures . DESIGN Prospect i ve , placebo-controlled , double-blind , multicenter r and omized trial with serial serum creatinine levels measured at a central biochemistry laboratory ( at baseline and 1 , 24 , 48 , and 72 to 96 hours after study drug administration ) and 30-day clinical follow-up . PATIENTS AND SETTING Between March 2001 and July 2002 , 315 patients with creatinine clearance less than 60 mL/min ( 1.00 mL/s ) at 28 centers in the United States were r and omized to receive fenoldopam mesylate ( n = 157 ) or placebo ( n = 158 ) . INTERVENTIONS Patients were hydrated and r and omized to receive intravenous fenoldopam ( 0.05 microg/kg/min titrated to 0.10 microg/kg/min ) vs matching placebo , starting 1 hour prior to angiography and continuing for 12 hours . MAIN OUTCOME MEASURE Contrast-induced nephropathy , defined as an increase of 25 % or more in serum creatinine level within 96 hours postprocedure . RESULTS Mean ( SD ) patient age was 70 ( 11 ) years , and 49 % had diabetes mellitus . Mean ( SD ) baseline creatinine clearance was 29.0 ( 10.0 ) mL/min ( 0.48 [ 0.16 ] mL/s ) ( range , 7.5 - 56.8 mL/min [ 0.12 - 0.94 mL/s ] ) , and 157 ( 108 ) mL of contrast was administered during the procedures . The primary end point of contrast-induced nephropathy occurred in 33.6 % of patients assigned to receive fenoldopam vs 30.1 % assigned to receive placebo ( relative risk , 1.11 ; 95 % confidence interval , 0.79 - 1.57 ; P = .61 ) . There were no significant differences in the 30-day rates of death ( 2.0 % vs 3.8 % , P = .50 ) , dialysis ( 2.6 % vs 1.9 % , P = .72 ) , or rehospitalization ( 17.6 % vs 19.9 % , P = .66 ) in fenoldopam vs placebo r and omized patients , respectively . CONCLUSION The selective dopamine-1 agonist fenoldopam mesylate does not prevent further renal function deterioration after contrast administration in patients with chronic renal insufficiency Background : Besides adequate analgesia , sedation and ventilation , postcardiac surgical hypertension has to be treated frequently with vasoactive drugs to avoid possible complications . In this study the hemodynamic effects of the DA1‐receptor agonist fenoldopam ( F ) are compared to those of the Ca‐channel antagonist nifedipine ( N ) Each year , 600 000 patients undergo myocardial revascularization with cardiopulmonary bypass and sustain profound physiologic perturbations that precipitate ischemia and infa rct ion in several organ systems [ 1 - 3 ] . Although medical re sources have been redirected to address perioperative cardiac and neurologic illness , the clinical effect of cardiac surgery on renal function has not been studied rigorously . Nonpulsatile blood flow , increases in levels of circulating catecholamines and inflammatory mediators , macroembolic and microembolic insults to the kidney , and release of free hemoglobin from traumatized erythrocytes result in numerous pathophysiologic renal responses [ 4 - 6 ] . Many studies [ 7 - 9 ] have shown that patients who have undergone cardiac surgery developed maldistributed renal blood flow , increases in renal vascular resistance , and substantive decreases ( 25 % to 75 % ) in renal blood flow and glomerular filtration rate . The effect of these phenomena on clinical outcome is not well known but is thought to be considerable . Studies have reported incidences of oliguric renal failure requiring dialysis as high as 5 % and mortality rates as great as 89 % . Previous studies [ 10 - 19 ] have many limitations because of a wide variability ( threefold or more ) in estimates of adverse renal outcomes : All of the studies were conducted at a single center , most were retrospective , and most were done more than a decade ago . No previous study provided adjusted estimates of risk factors ; in addition , the definition chosen for renal dysfunction was arbitrary , or the study sample consisted only of patients requiring dialysis [ 11 , 13 , 15 - 17 ] . Finally , few studies have investigated re source utilization in patients with renal dysfunction or failure . We therefore studied 2400 patients who underwent myocardial revascularization with cardiopulmonary bypass . Our goals were to determine 1 ) the incidence and characteristics of postoperative renal dysfunction and failure , 2 ) the predictors of renal dysfunction [ determined by the use of multivariate modeling techniques ] , and 3 ) the effect of renal dysfunction on in-hospital re source utilization and patient disposition after discharge . Methods Patients The Multicenter Study for Perioperative Ischemia ( McSPI ) Research Group studied 2417 patients undergoing myocardial revascularization between 1991 and 1993 . Twenty-four diverse U.S. health care facilities-small and large academic institutions , private medical centers , health maintenance organization groups , and Veterans Affairs hospitals-participated in this study . Most patients were representative of consecutive patients seen at a given medical center . We enrolled every nth patient on the basis of a proportion of the site-specific expected annual caseload ( n = 2 through 30 in 24 centers ) . Comprehensive data were collected from preoperative cardiac , surgical , and medical histories ; invasive and noninvasive cardiologic testing ; surgical procedures and techniques ; perioperative hemodynamic events ; postoperative in-hospital events ( illness and death ) ; and hospital re source utilization . In addition , serial preoperative and postoperative 12-lead electrocardiograms were obtained and were central ly analyzed by a consensus panel of cardiologists . Serum creatinine values were recorded before and after surgery . Of the 2417 patients enrolled , 195 were excluded from analysis because of preexisting renal failure ( n = 99 ) or dysfunction ( serum creatinine level > 177 mol/L [ n = 81 ] ) or lack of perioperative serum creatinine measurements ( n = 68 ) . The latter group included patients who died before a postoperative sample could be obtained . Definitions of Renal Failure , Renal Dysfunction , and Comorbid Events Postoperative renal failure was defined by the need for dialysis after surgery . Renal dysfunction was defined as a postoperative serum creatinine level of 177 mol/L or greater and an increase in serum creatinine level of 62 mol/L or greater from preoperative to maximum postoperative values . The criteria for dysfunction were derived from the distribution of serum creatinine values in an uncomplicated patient subset . This subset excluded patients with preoperative renal disease ( serum creatinine level > 124 mol/L ) or medical risk factors ( age > 70 years ; history of congestive heart failure or type 1 diabetes mellitus ) , or a complicated postsurgical course ( in-hospital death ; concomitant valvular surgery ; intraaortic balloon pump insertion ; administration of at least three nonroutine inotropic drugs ; measures of hemodynamic instability ; ventricular fibrillation or dysrhythmia requiring a pacemaker ; complications necessitating a return to cardiopulmonary bypass , the intensive care unit , or the operating room ; or chest tube output exceeding 1 L/d ) . Less than 1 % of patients meeting these criteria had a maximum postoperative creatinine level greater than 177 mol/L and a maximum preoperative-to-postoperative change in creatinine level of 62 mol/L. Comorbid events , assessed through the first postoperative day , consisted of postoperative myocardial infa rct ion , congestive heart failure ( hemodynamic or clinical ) , use of an intraaortic balloon pump or other mechanical circulatory assist device , administration of three or more inotropic drugs , and hemorrhage . A myocardial infa rct ion was defined as either a Q-wave or a non-Q-wave infa rct ion . A Q-wave myocardial infa rct ion was diagnosed central ly by the presence of a new Q wave on each of two postoperative 12-lead electrocardiograms , as defined by Minnesota Code criteria , that were scored by a consensus panel of cardiologists . A non-Q-wave myocardial infa rct ion was determined by an elevated creatine kinase-MB level , a new wall-motion abnormality detected by echocardiography , or a new perfusion defect on a scintigraphy scan . Low output state [ an ordered , categorical variable ] was defined as one of the following : 1 ) severe ventricular dysfunction-intraaortic balloon pump counterpulsation required , 2 ) moderate ventricular dysfunction-hemodynamic congestive heart failure or at least three nonroutine inotropic drugs prescribed after surgery , and 3 ) mild ventricular dysfunction- clinical congestive heart failure . We defined hemodynamic congestive heart failure on the basis of a cardiac index less than 1.5 L/min per m2 body surface area for at least 30 minutes , a central venous pressure greater than 12 mm Hg , or a pulmonary artery occlusion pressure/left ventricular end diastolic pressure greater than 18 mm Hg . Clinical congestive heart failure was defined according to the presence of pulmonary rales , S3 gallop , or chest radiographic findings suggestive of heart failure . We defined hemorrhage as 1 ) chest tube output of at least 1 L/d , 2 ) return to the critical care unit or operating room within the first postoperative day because of bleeding , or 3 ) administration of three or more units of blood products in the operating room or critical care unit within 48 hours of surgery . Statistical Analysis Distributions and univariate measures of preoperative , postoperative , and preoperative-to-postoperative changes in serum creatinine values were examined . Unadjusted relative risks and 95 % CIs were calculated for all perioperative factors . Adjusted relative risk estimates were derived from multivariate logistic regression models because an 8 % incidence of renal dysfunction is relatively rare . Models were analyzed in a piece-wise fashion ( separate models were developed for each preoperative , operative , and postoperative period from the significant unadjusted factors in each period ) . A final model with adjusted estimates of relative risk was derived with factors that remained significant ( P 0.05 ) in the three time period models . Operative and postoperative variables were entered into the model in a forward stepwise fashion after adjustment for preoperative variables . No appreciable differences were noted when all perioperative factors were allowed to enter into the model in forward or backward stepwise selection procedures . The best-fitting models were selected from evaluation of the Hosmer-Lemeshow goodness-of-fit test statistic and the smallest values of the Akaike Information Criterion . The predictive ability of the models of preoperative risk factors alone , as well as the final model , were also evaluated with the area under the receiver-operating characteristic curve ( the concordance or c-index ) . The c-index was also derived from a validation process that involved comparison of the c-index derived from a r and om sample of half of the patients from each site and a computed c-index derived from modeling the remaining sample 's predicted probability of renal dysfunction calculated from the variable estimates from the original 50 % r and om sample . In other words , a predicted probability was derived from variable estimates from those obtained from the 50 % within-center sample ; these estimates were applied to the patients ' combination of risk factors in the remaining sample . The c-index was then calculated from modeling the remaining sample 's predicted probabilities as a single predictor . From the final model of preoperative risk factors , both observed and predicted probabilities were described and the sensitivity and specificity of the preoperative model were reported . The sensitivity and specificity were determined by selecting the highest sensitivity and specificity from a classification table of observed and predicted events ( this occurred with a probability of renal dysfunction 6 % ) . Theoretically , each of the 24 medical centers in the study sample may have characteristics that were not measured and could have influenced patients ' outcomes . To address potential within-center correlation , ancillary analyses were conducted . Logistic regression models using generalized estimating equations with an exchangeable correlation matrix were used to account for within-center correlation . Estimates of SEs are considered corrected for potential within-center BACKGROUND Acute tubular necrosis ( ATN ) occurs commonly in critically ill patients and is associated with increased morbidity and mortality . Fenoldopam is a dopamine receptor alpha1-specific agonist that increases renal blood flow in patients with kidney failure . We hypothesized that administration of low-dose fenoldopam during early ATN would decrease the need for dialysis therapy and /or incidence of death at 21 days . METHODS We conducted a prospect i ve , r and omized , double-blind , placebo-controlled , clinical trial in 155 patients with early ATN . Patients were considered eligible for enrollment if serum creatinine level increased to 50 % greater than admission levels within 24 hours and mean arterial pressure was greater than 70 mm Hg . Patients were r and omly assigned to the administration of placebo or fenoldopam for 72 hours . RESULTS Overall , 22 of 80 patients ( 27.5 % ) in the fenoldopam group reached the primary end point compared with 29 of 75 patients ( 38.7 % ) in the placebo group ( P = 0.235 ) . This 11 % absolute reduction in the primary end point was not statistically significant ( P = 0.23 ) . Similarly , there was no difference in the incidence of dialysis therapy between patients r and omly assigned to fenoldopam ( 13 of 80 patients ; 16.25 % ) versus the placebo group ( 19 of 75 patients ; 25.3 % ; P = 0.163 ) . Moreover , there was no statistically significant difference in 21-day mortality rates between the 2 groups ( fenoldopam , 13.8 % versus placebo , 25.3 % ; P = 0.068 ) . In secondary analyses , fenoldopam tended to reduce the primary end point in patients without diabetes and postoperative cardiothoracic surgery patients with early ATN ( fenoldopam patients without diabetes , 14 of 54 patients [ 25.9 % ] versus placebo patients without diabetes , 23 of 52 patients [ 44.2 % ] ; P = 0.048 ) and postoperative cardiothoracic patients ( 6 of 34 patients [ 17.6 % ] versus 14 of 36 patients [ 38.8 % ] ; P = 0.049 ) . Conversely , fenoldopam did not improve the primary end point in patients with diabetes or those with acute renal failure from other causes . A larger multicenter trial using separate r and omizations for patients with and without diabetes will be needed to determine the efficacy of fenoldopam mesylate in specific sub population s with ATN . CONCLUSION Fenoldopam does not reduce the incidence of death or dialysis therapy in intensive care unit patients with early ATN Summary The effects of chronic oral fenoldopam in the treatment of NYHA grade II – III heart failure secondary to ischaemic heart disease , were studied in a placebo controlled , double blind , r and omised , parallel group fashion in 20 patients . Nine patients taking placebo and six taking fenoldopam completed the study .Adverse events were similar in each group . There were no significant changes in exercise capacity , ejection fraction , body weight or symptom question naires with either treatment . This preliminary study has not revealed any benefit of fenoldopam in heart failure due to ischaemic heart disease PURPOSE Patients with hypertensive crises often experience reduced renal function that may worsen as the elevated blood pressure is treated . Fenoldopam , a novel , peripherally acting dopamine-1 agonist , lowers blood pressure through arteriolar vasodilation , with particularly prominent effects on the renal vascular bed . This study was conducted to examine the effects of fenoldopam on blood pressure and renal function compared to those of sodium nitroprusside in severely hypertensive patients with impaired renal function . PATIENTS AND METHODS Renal function and systemic hemodynamics were studied in 19 severely hypertensive patients ( diastolic blood pressure greater than or equal to 120 mm Hg ) with impaired renal function ( creatinine clearance less than or equal to 70 mL/min ) enrolled in clinical trials of fenoldopam and sodium nitroprusside . For comparison , an additional 22 severely hypertensive patients with nonimpaired renal function were studied under the same conditions . Blood pressure and heart rate were measured at baseline before treatment and periodically during treatment . Renal function was determined before and during drug infusion by collection of timed urine specimens and blood sample s. Creatinine clearance , urine flow rate , and sodium and potassium excretions were measured and compared . RESULTS In patients with impaired renal function , blood pressure ( mean + /- SEM ) was reduced successfully in both groups ( fenoldopam : 214 + /- 8/139 + /- 6 mm Hg to 176 + /- 8/107 + /- 3 mm Hg , p < 0.001 for systolic and diastolic comparisons ; nitroprusside : 226 + /- 4/145 + /- 5 mm Hg to 171 + /- 6/108 + /- 2 mm Hg , p < 0.001 for systolic and diastolic comparisons ) . Results of renal function studies showed significant increases in creatinine clearance ( from 39 + /- 7 mL/min to 75 + /- 16 mL/min , p < 0.05 ) , urine flow ( from 119 + /- 37 mL/h to 275 + /- 84 mL/h , p < 0.01 ) , and sodium excretion ( from 75 + /- 22 microEq/min to 227 + /- 60 microEq/min , p < 0.01 ) in patients with impaired renal function treated with fenoldopam . No significant changes were seen in patients treated with nitroprusside . In patients with nonimpaired renal function , blood pressure was reduced by both agents , but only patients who received fenoldopam experienced significant increases in creatinine clearance , urine flow rate , and sodium excretion . CONCLUSION Fenoldopam , but not nitroprusside , improved renal function in severely hypertensive patients at all levels of baseline renal function while lowering blood pressure . Because of these effects , fenoldopam may be particularly useful in treating severely hypertensive patients with impaired renal function Background Mechanical ventilation with positive end-expiratory pressure ( PEEP ) can impair renal hemodynamics . Fenoldopam , a dopamine receptor agonist , has been shown , in animal experiments , to improve renal perfusion . The purpose of the current study was to examine the effects of this agent on altered renal hemodynamics secondary to positive pressure ventilation Methods Twelve patients requiring mechanical ventilation of their lungs and PEEP for the treatment of hypoxemia after multiple trauma or visceral surgery were studied . Hemodynamic variables , renal vascular resistance , urine flow , creatinine , inulin and PAH clearance , and excretion of sodium and potassium ( NaE and KE ) were measured before and after Introduction of a level of PEEP high enough to decrease urine flow rate by 25 % or more , and after administration of intravenous fenoldopam . Results No hemodynamic effect result ed from 0.1 μg · kg−1 , but 0.2 μg · Kg−1 · min−1 fenoldopam decreased both diastolic and mean arterial blood pressure from 66 ± 37 ( mean ± SEM ) to 57 ± 21 mmHg , and from 83 ± 3 to 74 ± 4 mmHg , respectively . Renal vascular resistance was reduced from 54 ± 12 to 19 ± 5 dynes · s · cm-5 at 0.2 μg · kg−1 · min−1 . Fenoldopam produced a dose-related Increase in renal blood flow and PAH clearance . With 0.2 μg · kg−1 · min−1 fenoldopam , urine flow increased from 81 ± 25 to 116 ± 29 ml/h , NaE from 28 ± 7 to 85 ± 70 μM/min , and KE from 65 ± 12 to 109 ± 16 μM/min . Conclusions The results of the current study indicate that intravenous fenoldopam at a dose of 0.2 μg · kg−1 · min−1 improves renal hemodynamics and increases Na and K excretion in patients requiring mechanical ventilation of their lungs and PEEP . These effects are probably caused by an increased kidney perfusion secondary to renal artery vasodilation Delayed renal allograft function ( DGF ) is a factor for acute rejection and chronic allograft nephropathy . Cold ischemia time ( CIT ) is associated with an increased in DGF . Twenty patients receiving allografts with CIT>12 were enrolled in a double-blinded , r and omized ( 1:1 ) , placebo-controlled study to assess vasodilatation with fenoldopam ( Abbott ; dopamine-1 receptor agonist ) on DGF . Fenoldopam infusion began at arterial anastomosis at 0.025 microg/kg/min and titrated to 0.1 microg/kg/min continued for 48 h postop ( PO ) . Immunosuppression included steriods , MMF , and calcinurin inhibitors begun 36 h PO . Antibody induction ( AI ) using antithymocyte globulin ( rabbit ) ( AT-G(r ) ; Sangstat ) was added halfway through the study to African-Americans and for PRA>40 % . The need for dialysis , cumulative urine output ( UOP ) , and creatinine ( Cr ) at PO day 7 , 14 , and 30 were compared . Eighteen patients completed the study drug infusion . Demographics of groups were not different . There was no difference between fenoldopam and controls for dialysis , UOP at 48 and 72 h , or Cr at 7 , 14 , or 30 days . There was a difference in UOP when AI ( n=7 ) was compared to non-AI ( n=11 ) . At 48 h non-AI UOP 4796+/-3284 ml compared to AI UOP 8960+/-5130 ml ( p=0.050 ) . At 72 h , non-AI patients had UOP of 6824+/-4547 ml compared to AI patients with UOP of 12196+/-5868 ml ( p=0.044 ) . There was a trend to a lower Cr at day 7 for AI 2.7+/-2.1mg/dl compared to 4.9+/-3.0 mg/dl in non-AI ( p=0.11 ) . There was no difference in dialysis or Cr at day 14 and 30 between the AI and non-AI patients . AI with AT-G(r ) significantly increases UOP in allografts with CIT>12 h , whereas vasodilatation did not . Therapy for DGF may include AT-G(r ) AI BACKGROUND Radiocontrast nephropathy ( RCN ) is a common source of acute renal failure in hospitalized patients and is associated with increased morbidity and mortality rates . Fenoldopam mesylate is a dopamine A1 receptor agonist that augments renal plasma flow ( RPF ) in patients with normotensive and hypertensive conditions . To determine whether fenoldopam mesylate attenuates reductions in RPF after contrast infusion , we conducted a double-blind , r and omized , placebo-controlled pilot trial of fenoldopam mesylate in patients who underwent contrast angiography . METHODS Fifty-one patients with chronic renal insufficiency ( creatinine level , 2.0 - 5.0 mg/dL ) who were undergoing contrast angiography were screened , and 45 patients were r and omized to receive normal saline solution ( 1/2 NS ) or 1/2 NS plus fenoldopam mesylate at 0.1 microg/kg/min at lease 1 hour before infusion with contrast dye . Serum creatinine level was measured at baseline and at 24 , 48 , and 72 hours after angiography . The primary endpoint was change in RPF 1 hour after contrast infusion . The secondary endpoint was incidence of RCN , defined as a 0.5 mg/dL or a 25 % rise in serum creatinine level at 48 hours . RESULTS RPF at 1 hour after angiography was 15.8 % above baseline in the fenoldopam mesylate group compared with 33.2 % below baseline in the 1/2 NS group ( P < .05 ) . The incidence rate of RCN at 48 hours was 41.0 % in the 1/2 NS group versus 21 % in the fenoldopam mesylate group ( P = .148 ) . Among patients with diabetes , the incidence rate of RCN tended to be higher in the 1/2 NS group compared with the fenoldopam mesylate group ( 64 % vs 33 % ; P = .14 ) . The peak serum creatinine level at 72 hours after contrast infusion was significantly higher at in the 1/2 NS group ( creatinine level , 3.6 + /- 1.0 mg/dL ) compared with the fenoldopam mesylate group ( creatinine level , 2.8 + /- 0.35 mg/dL ; P < .05 ) . RPF was significantly ( P < .0001 ) reduced in patients with RCN compared with patients in whom RCN did not develop . CONCLUSION The results of this pilot trial suggest that fenoldopam mesylate is a promising prophylactic agent for RCN and that larger multicenter trials should be conducted to prove its efficacy BACKGROUND Patients with acute renal failure ( ARF ) have high morbidity and mortality rates , particularly if they have serious comorbid conditions . Several studies indicate that in rats with ARF caused by ischemia or certain nephrotoxins , insulin-like growth factor-I ( IGF-I ) enhances the recovery of renal function and suppresses protein catabolism . METHODS Our objective was to determine whether injections of recombinant human IGF-I ( rhIGF-I ) would enhance the recovery of renal function and is safe in patients with ARF . The study was design ed as a r and omized , double-blind , placebo-controlled trial in intensive care units in 20 teaching hospitals . Seventy-two patients with ARF were r and omized to receive rhIGF-I ( 35 patients ) or placebo ( 37 patients ) . The most common causes of ARF in the rhIGF-I and placebo groups were , respectively , sepsis ( 37 and 35 % of patients ) and hypotension or hemodynamic shock ( 42 and 27 % of patients ) . At baseline , the mean ( + /- SD ) APACHE II scores in the rhIGF-I and placebo-treated groups were 24 + /- 5 and 25 + /- 8 , respectively . In the rhIGF-I and placebo groups , the mean ( median ) urine volume and urinary iothalamate clearances ( glomerular filtration rate ) were 1116 + /- 1037 ( 887 ) and 1402 + /- 1183 ( 1430 ) ml/24 hr and 6.4 + /- 5.9 ( 4.3 ) and 8.7 + /- 7.2 ( 4.4 ) ml/min and did not differ between the two groups . Patients were injected subcutaneously every 12 hours with rhIGF-I , 100 microgram/kg desirable body weight , or placebo for up to 14 days . Injections were started within six days of the onset of ARF . The primary end-point was a change in glomerular filtration rate from baseline . Other end points included changes from baseline in urine volume , creatinine clearance and serum urea , creatinine , albumin and transferrin , frequency of hemodialysis or ultrafiltration , and mortality rate . RESULTS During the treatment period , which averaged 10.7 + /- 4.1 and 10.6 + /- 4.5 days in the rhIGF-I and placebo groups , there were no differences in the changes from baseline values of the glomerular filtration rate , creatinine clearance , daily urine volume , or serum urea nitrogen , creatinine , albumin or transferrin . In patients who did not receive renal replacement therapy , there was also no significant difference in serum creatinine and urea between the two groups . Twenty patients in the rhIGF-I group and 17 placebo-treated patients underwent dialysis or ultrafiltration . Twelve rhIGF-I-treated patients and 12 placebo-treated patients died during the 28 days after the onset of treatment . CONCLUSIONS rhIGF-I does not accelerate the recovery of renal function in ARF patients with substantial comorbidity Objective : Acute renal failure is common in septic patients . Fenoldopam , a dopamine-1 receptor agonist , increases renal blood flow and may , therefore , reduce the risk of acute renal failure in such patients . Accordingly , we sought to determine the safety and efficacy of fenoldopam for the prevention of acute renal failure in septic patients . Design : Prospect i ve , double-blind , placebo-controlled trial . Setting : Three multidisciplinary intensive care units at a university hospital . Patients : Three hundred septic patients with baseline serum creatinine concentrations < 150 & mgr;mol/L. Interventions : We r and omized patients to a continuous infusion of either fenoldopam ( n = 150 ) at 0.09 & mgr;g·kg−1·min−1 or placebo ( n = 150 ) while in the intensive care unit . The primary outcome measure was the incidence of acute renal failure , defined as a serum creatinine concentration increase to > 150 & mgr;mol/L , during study drug infusion . Measurements and main results : The incidence of acute renal failure was significantly lower in the fenoldopam group compared with the control group ( 29 vs. 51 patients ; p = .006 ) . The odds ratio of developing acute renal failure for patients treated with fenoldopam was estimated to be 0.47 ( p = .005 ) . The difference in the incidence of severe acute renal failure ( creatinine > 300 & mgr;mol/L ) , however , failed to achieve statistical significance ( 10 vs. 21 ; p = .056 ) . The length of intensive care unit stay in surviving patients was significantly lower in the fenoldopam group compared with the control group ( 10.64 ± 9.3 vs. 13.4 ± 14.0 ; p < .001 ) . There were no complications of fenoldopam infusion . A direct effect of treatment on the probability of death , beyond its effect on acute renal failure , was not significant ( odds ratio = 0.68 , p = .1 ) . Conclusions : Compared with placebo , low-dose fenoldopam result ed in a smaller increase in serum creatinine in septic patients . The clinical significance of this finding is uncertain . A large multiple-center trial is now needed to confirm these findings Dopamine1 receptors mediate hemodynamic effects that may be beneficial in patients with congestive heart failure . We infused the selective dopamine1 receptor agonist , fenoldopam mesylate ( SKF 82526 J ) , to evaluate hemodynamic and neurohumoral changes during continuous intravenous infusion in patients with congestive heart failure and compared them with the effects of nitroprusside , a traditional vasodilator that works by a distinctly different mechanism . In 15 patients with a mean radionuclide ejection fraction of 17 % , the agents were infused in a r and om-ordered , double-blinded , crossover , active drug-controlled protocol after optimal dosing was determined during a titration period . Hemodynamic changes were induced in minutes with both drugs during a mean ( + /- st and ard deviation ) infusion dose of 1.45 + /- 1.66 micrograms/kg/min for fenoldopam and 2.99 + /- 1.59 micrograms/kg/min for nitroprusside . At 1 hour , mean blood pressure decreased and cardiac index rose with both drugs , and the effect lasted throughout the 6-hour infusion period . Nitroprusside , but not fenoldopam , reduced right heart filling pressures ( including mean pulmonary capillary wedge , mean right atrial , and mean pulmonary artery pressures ) during the infusion period . Both drugs caused significant reduction in systemic vascular and pulmonary arteriolar resistances . No significant change occurred in plasma norepinephrine levels . Fenoldopam ameliorates some of the adverse hemodynamic changes that occur during heart failure but does not reduce right heart filling pressures as does nitroprusside . Because of fenoldopam 's unique characteristics , it may benefit certain patients with heart failure Cyclosporine causes renal vasoconstriction and reduced renal blood flow that may contribute to chronic nephrotoxicity . This effect has not been consistently reversed by available pharmacologic agents . The efficacy of orally administered fenoldopam , a dopamine-1 ( DA-1 ) agonist with renal vasodilator properties , was evaluated in six patients whose condition was stable 3 to 6 months following renal transplantation . Glomerular filtration rate ( GFR ) and effective renal plasma flow ( ERPF ) were measured by inulin and p-aminohippurate ( PAH ) clearances , respectively , at baseline , after the acute oral administration of 100 mg of fenoldopam , and following 3 weeks of chronic oral fenoldopam therapy ( 100 mg thrice daily ) . Mean ERPF increased from 3.15 + /- 0.17 mL/s/1.73 m2 ( 189 + /- 10 mL/min/1.73 m2 ) at baseline to 3.48 + /- 0.17 mL/s/1.73 m2 ( 209 + /- 10 mL/min/1.73 m2 ) 4 hours after acute administration of fenoldopam ( P = 0.04 ) . Urine flow rate and fractional excretion of sodium also increased after acute administration , but not significantly . Mean systolic ( SBP ) and diastolic blood pressure ( DBP ) decreased maximally by 18 and 6 mm Hg , respectively , and mean pulse rate increased maximally by 8 bpm between 75 and 90 minutes after both acute and chronic administration . GFR was unchanged following both acute and chronic administration . The increase in ERPF was not maintained to the end of the dosing interval during chronic administration , probably due to the short half-life of fenoldopam . However , the renal vasodilatory response was still observed 3 to 4 hours after readministration of the drug following 3 weeks of oral dosing . Thus , fenoldopam significantly reverses the renal vasoconstriction caused by cyclosporine in renal transplant recipients . ( ABSTRACT TRUNCATED AT 250 WORDS A prospect i ve trial to compare the effects of the synthetic dopaminergic ( DA1 ) agonist , fenoldopam ( FEN ) , with sodium nitroprusside ( SNP ) for control of blood pressure following coronary artery bypass graft surgery was carried out in 20 patients . Patients were r and omly allocated to receive either FEN or SNP when the systolic arterial blood pressure ( SAP ) rose above 130 mmHg . The goal of therapy was to achieve a stable control of blood pressure below 130 mmHg at a level at least 25 mmHg below the pretreatment value . Treatment was then continued for 2 hours . Hemodynamic measurements were made before treatment , after stable control of blood pressure had been achieved , and thereafter at 30 , 60 , and 120 minutes . Urine output , sodium , potassium , and creatinine clearance were also measured during the study . Both SNP and FEN caused a rapid and significant fall in SAP ( P < 0.001 ) and a fall in systemic vascular resistance ( P < 0.001 ) . FEN caused an increase in cardiac index ( P < 0.001 ) and in stroke volume ( P < 0.001 ) in contrast to SNP . Urine output and potassium clearance fell with SNP ( P < 0.05 ) in contrast to FEN . Thus , FEN would appear to control SAP as effectively as SNP , but may have more beneficial effects on cardiac output and some aspects of renal function Dopamine receptor stimulation causes vascular and neurohumoral responses that may be beneficial in patients with heart failure . Oral inactivity , emesis and adrenergic-induced arrhythmias have limited the use of currently available compounds . Fenoldopam ( SKF-82526-J ) is a new , orally available , selective , dopamine-receptor agonist with potent renal vasodilating properties ( six times that of dopamine ) without positive inotropic or adrenergic activity . Drug efficacy was clinical ly evaluated in 10 patients with heart failure after single oral doses of placebo and 50 , 100 and 200 mg of medication . Placebo produced no changes . Peak efficacy was noted 30 minutes to 1 hour after the 200 mg dose with mean blood pressure decreasing from 96 + /- 15 ( mean + /- SD ) to 83 + /- 8 mm Hg ( p less than 0.05 ) , pulmonary capillary wedge pressure decreasing from 23 + /- 6 to 20 + /- 8 mm Hg ( p less than 0.05 ) and mean pulmonary artery pressure decreasing from 32 + /- 9 to 29 + /- 8 mm Hg ( p less than 0.05 ) . Systemic vascular resistance decreased from 1,987 + /- 887 to 1,191 + /- 559 dynes.s.cm-5 ( p less than 0.05 ) with a subsequent 55 % increase in cardiac index from 2.2 + /- 1.1 to 3.1 + /- 1.3 liters/min per m2 ( p less than 0.05 ) . Heart rate and right atrial pressure did not change ( p greater than 0.05 ) . No emesis or new tachycardia was noted at any dose . Baseline hemodynamics generally returned within 3 to 4 hours . Fenoldopam , therefore , is a short-acting , orally effective drug that decreases systemic vascular resistance and increases cardiac index in patients with heart failure and represents a new class of oral compounds that may be useful in treating such patients BACKGROUND Atrial natriuretic peptide , a hormone synthesized by the cardiac atria , increases the glomerular filtration rate by dilating afferent arterioles while constricting efferent arterioles . It has been shown to improve glomerular filtration , urinary output , and renal histopathology in laboratory animals with acute renal dysfunction . Anaritide is a 25-amino-acid synthetic form of atrial natriuretic peptide . METHODS We conducted a multicenter , r and omized , double-blind , placebo-controlled clinical trial of anaritide in 504 critically ill patients with acute tubular necrosis . The patients received a 24-hour intravenous infusion of either anaritide ( 0.2 microgram per kilogram of body weight per minute ) or placebo . The primary end point was dialysis-free survival for 21 days after treatment . Other end points included the need for dialysis , changes in the serum creatinine concentration , and mortality . RESULTS The rate of dialysis-free survival was 47 percent in the placebo group and 43 percent in the anaritide group ( P = 0.35 ) . In the prospect ively defined subgroup of 120 patients with oliguria ( urinary output , < 400 ml per day ) , dialysis-free survival was 8 percent in the placebo group ( 5 of 60 patients ) and 27 percent in the anaritide group ( 16 of 60 patients , P = 0.008 ) . Anaritide-treated patients with oliguria who no longer had oliguria after treatment benefited the most . Conversely , among the 378 patients without oliguria , dialysis-free survival was 59 percent in the placebo group ( 116 of 195 patients ) and 48 percent in the anaritide group ( 88 of 183 patients , P = 0.03 ) . CONCLUSIONS The administration of anaritide did not improve the overall rate of dialysis-free survival in critically ill patients with acute tubular necrosis . However , anaritide may improve dialysis-free survival in patients with oliguria and may worsen it in patients without oliguria who have acute tubular necrosis OBJECTIVE Acute renal failure , frequently a consequence of renal vasoconstriction and subsequent renal ischemia , is a common problem for which no proven preventive or therapeutic agents exist . Fenoldopam is a new , selective , dopamine-1 receptor agonist that causes both systemic and renal arteriolar vasodilation . In hypertensive patients , fenoldopam rapidly decreases blood pressure , increases renal blood flow , and maintains or improves the glomerular filtration rate . We sought to determine a dose of fenoldopam that increases renal blood flow without inducing hypotension in normotensive patients and to explore the role of volume status ( sodium replete vs. deplete ) in these effects . DESIGN R and omized , double-blind , placebo-controlled , cross-over study . SETTING Clinical research unit . PATIENTS Fourteen normal male volunteers . INTERVENTIONS Renal plasma flow ( para-aminohippurate clearance ) and glomerular filtration rate ( inulin clearance ) were measured during three fixed , escalating doses of fenoldopam ( 0.03 , 0.1 , and 0.3 Lg/kg/min ) on both a high-sodium and a low-sodium diet . MEASUREMENTS AND MAIN RESULTS Fenoldopam significantly increased renal plasma flow in a dose-dependent manner compared with placebo : 670 + 148 vs. 576 + 85 mUmin at 0.03 iLg/kg/min ; 777 + 172 vs. 579 + 80 mUmin at 0.1 tig/kg/min ; and 784 + 170 vs. 592 + 165 mUmin at 0.3 ilg/kg/min ( p < .05 fenoldopam vs. placebo at all three doses ) . Glomerular filtration rate was maintained . At the lowest dose ( i.e. , 0.03 ILg/kg/min ) , significant renal blood flow increases occurred without changes in systemic blood pressure or heart rate . At 0.1 and 0.3 Lgl/kg/ min , systolic blood pressure did not change , but diastolic blood pressure was slightly lower in the fenoldopam group than in the placebo group : 62.5 + 6.4 vs. 63.6 + 2.6 mm Hg , respectively , at 0.3 tg/kg/min ( p < .05 ) . None of the effects of fenoldopam were altered by volume status . CONCLUSIONS Fenoldopam increased renal blood flow in a dose-dependent manner compared with placebo , and , at the lowest dose , significantly increased renal blood flow occurred without changes in systemic blood pressure or heart rate . These findings will be useful in design ing future studies exploring the role of fenoldopam in preventing or treating renal failure in patients who are not hypertensive Objectives Acute renal failure is a complication in critically ill patients that has been associated with an excess risk of hospital mortality . Whether this reflects the severity of the disease or whether acute renal failure is an independent risk factor is unknown . The aim of this study was to analyze severity of illness and mortality in a group of critically ill patients with acute renal failure requiring renal replacement therapy in a number of Austrian intensive care units . Design Prospect i ve , multicenter cohort study . Patients and Setting A total of 17,126 patients admitted consecutively to 30 medical , surgical , and mixed intensive care units in Austria over a period of 2 yrs . Measurements and Main Results Analyzed data included admission data , Simplified Acute Physiology Score , Logistic Organ Dysfunction system , Simplified Therapeutic Intervention Scoring System , length of intensive care unit stay , intensive care unit mortality , and hospital mortality . Of the admitted patients , 4.9 % ( n = 839 ) underwent renal replacement therapy because of acute renal failure ( renal replacement therapy patients ) . These patients had a significantly higher hospital mortality ( 62.8 % vs. 15.6 % , p < .001 ) , which remained significantly higher even when renal replacement therapy patients were matched with control subjects for age , severity of illness , and treatment center . Since univariate analysis demonstrated further intensity of treatment to be an additional predictor for outcome , a multivariate model including therapeutic interventions was developed . Five interventions were associated with nonsurvival ( mechanical ventilation , single vasoactive medication , multiple vasoactive medication , cardiopulmonary resuscitation , and treatment of complicated metabolic acidosis/alkalosis ) . In contrast , the use of enteral nutrition predicted a favorable outcome . Conclusions The results of our study suggest that acute renal failure in patients undergoing renal replacement therapy presents an excess risk of in-hospital death . This increased risk can not be explained solely by a more pronounced severity of illness . Our results provide strong evidence that acute renal failure presents a specific and independent risk factor for poor prognosis BACKGROUND Acute renal failure requiring replacement therapy occurs in 1 % to 2 % of patients who have undergone cardiac surgery with cardiopulmonary bypass and is associated with a very high mortality rate . The aim of this study was to determine if prophylactic treatment with fenoldopam mesylate of patients at high risk of postoperative acute renal failure reduced the incidence of this event . METHODS This was a multicenter , prospect i ve , cohort study in which 108 patients at high risk of postoperative acute renal failure and undergoing cardiac surgery with cardiopulmonary bypass were treated with fenoldopam mesylate ( 0.08 microg x kg(-1 ) x min(-1 ) ) starting at the induction of anesthesia and throughout at least the next 24 hours . A homogeneous control group of 108 patients was created using a propensity-score analysis . RESULTS Fenoldopam prophylaxis was significantly associated with a reduction in acute renal failure incidence ( from 22 % to 11 % , p = 0.028 ) , a less pronounced creatinine clearance decrease ( p = 0.05 ) , and a lower mortality rate ( 6.5 % versus 15.7 % , p = 0.03 ) by the univariate analysis , but these results were not confirmed by a multivariable analysis . Within the subgroup of patients who suffered a postoperative low output syndrome , fenoldopam prophylaxis was an independent protective factor for postoperative renal failure ( odds ratio , 0.14 ; 95 % confidence interval , 0.03 to 0.7 ; p = 0.017 ) . CONCLUSIONS Given the limitations of a nonr and omized prospect i ve trial , our results support the hypothesis that fenoldopam may reduce the risk of acute renal failure in patients in whom endogenous and exogenous cathecolamines action may induce a renal vascular constrictive condition OBJECTIVE To evaluate the usefulness of low-dose fenoldopam mesylate in patients at risk of developing renal dysfunction after cardiac surgery requiring cardiopulmonary bypass . DESIGN A prospect i ve , single-center , observational study . SETTING University teaching hospital . PARTICIPANTS Seventy patients scheduled for elective cardiac surgery with one or more predefined risk factors for renal dysfunction . INTERVENTIONS After induction of anesthesia , fenoldopam ( 0.03 microg/kg/min ) was administered throughout surgery and into the postoperative period , until the patient was stable and weaned from all other vasoactive agents . Perioperatively , fenoldopam was also used as a second-line antihypertensive agent as required . MEASUREMENTS AND MAIN RESULTS No patient developed renal failure that required dialysis , whereas 7.1 % ( 5/70 ) developed non-dialysis-dependent renal dysfunction . Four out of these 5 patients had 2 or more risk factors ( 9.5 % ) . Higher preoperative creatinine levels , a history of hypertension , myocardial infa rct ion within 5 days of surgery , and a preoperative diagnosis of chronic renal insufficiency were all good predictors of postoperative non-dialysis-dependent renal dysfunction . Discharge serum creatinine levels were lower than preoperative levels ( 1.16 + /- 0.36 mg/dL v 1.26 + /- 0.34 mg/dL , p < 0.05 ) . CONCLUSION These findings suggest that renal function was preserved in patients at increased risk for renal dysfunction after cardiac surgery when low-dose fenoldopam was used in the perioperative period . However , a r and omized , controlled trial is required to establish efficacy Objective : Acute renal failure is associated with significant morbidity and mortality rates . Need for dialysis is an independent risk factor for early mortality after complicated cardiac surgery . Human atrial natriuretic peptide ( h-ANP ) is a potent endogenous natriuretic and diuretic substance . Exogenous administration of h-ANP increases glomerular filtration rate and renal blood flow in clinical acute renal failure . We have studied the effects of h-ANP on renal outcome in ischemic acute renal failure . Design : A prospect i ve , double-blind , r and omized , placebo-controlled study . Setting : Cardiothoracic intensive care units of two tertiary care centers . Patients : Sixty-one patients with normal preoperative renal function suffering from postcardiac surgical heart failure requiring significant inotropic and vasoactive support . Interventions : The patients were r and omized to receive a continuous infusion of either recombinant h-ANP ( 50 ng·kg−1·min−1 ) or placebo when serum creatinine increased by > 50 % from baseline . The treatment with h-ANP/placebo continued until serum creatinine decreased below the trigger value for inclusion or the patients fulfilled predefined criteria for dialysis . Measurements and Main Results : The primary outcome variable was dialysis on or before day 21 after the start of treatment . Secondary renal outcome variables were dialysis-free survival at day 21 and creatinine clearance . Twenty-nine patients were assigned h-ANP and 30 placebo . Six ( 21 % ) patients in the h-ANP group compared with 14 ( 47 % ) in the placebo group needed dialysis before or at day 21 ( hazard ratio , 0.28 ; 95 % confidence interval , 0.10–0.73 ; p = .009 ) . Eight ( 28 % ) patients in the h-ANP group compared with 17 ( 57 % ) in the placebo group suffered from the combined end point dialysis or death before or at day 21 ( hazard ratio , 0.35 ; 95 % confidence interval , 0.14–0.82 ; p = .017 ) . h-ANP improved creatinine clearance in contrast to placebo ( p = .040 ) . Conclusions : Infusion of h-ANP at a rate of 50 ng·kg−1·min−1 enhances renal excretory function , decreases the probability of dialysis , and improves dialysis-free survival in early , ischemic acute renal dysfunction after complicated cardiac surgery OBJECTIVE To evaluate the possible protective effects of fenoldopam on renal function in patients undergoing cardiopulmonary bypass . DESIGN Prospect i ve , r and omized trial . SETTING University teaching hospital . PARTICIPANTS One hundred sixty consecutive patients with serum creatinine > 1.5 mg/dL who underwent uncomplicated moderate hypothermic cardiopulmonary bypass for cardiac surgery . INTERVENTIONS A r and om group of 80 patients was managed conventionally ( group A ) , whereas another r and om group of 80 patients received continuous intravenous administration of low-dose fenoldopam ( 0.1 - 0.3 microg/kg/min ) during cardiopulmonary bypass and in the early postoperative period ( group B ) . MEASUREMENTS AND MAIN RESULTS An improvement of postoperative renal parameters were observed only in group B : preoperative serum creatinine 1.82 + /- 0.2 versus 1.43 + /- 0.73 postoperatively ( p < 0.001 ) , preoperative creatinine clearance 51.34 + /- 22.26 versus 67.14 + /- 18.55 postoperatively ( p < 0.001 ) . CONCLUSIONS In this study , fenoldopam was an effective agent in the prevention of renal dysfunction after cardiopulmonary bypass STUDY OBJECTIVE To examine the safety and efficacy of intravenous fenoldopam as compared to placebo for the treatment of postoperative hypertension . DESIGN R and omized , placebo-controlled , double-blind study . SETTING Community hospital . PATIENTS 16 ASA I-III hypertensive patients scheduled for noncardiac surgical procedures . INTERVENTIONS Treatment with fenoldopam or placebo was initiated immediately after other causes of hypertension had been ruled out . Hypertension was defined as a supine systolic blood pressure ( SBP ) or diastolic blood pressure ( DBP ) greater than 20 % over the patient 's preoperative baseline , which was obtained 6 hours prior to the procedure with the patient lying quietly . The baseline consisted of 3 consecutive blood pressure ( BP ) measurements obtained at 5-minute intervals and not varying by more than 10 % . Fenoldopam or placebo infusion was initiated at 0.1 microgram/kg/min and increased and decreased as necessary until the therapeutic goal BP was reached or treatment failure had occurred . The therapeutic goal BP was a decrease to at least 10 % above the preoperative baseline , and failure of treatment was defined as inability to reach this BP level after 15 minutes at 1.5 micrograms/kg/min . MEASUREMENTS AND MAIN RESULTS BP and heart rate ( HR ) data were collected consistently throughout the study and 1 hour after termination of infusion . Laboratory studies and 12-lead electrocardiographic results were obtained at the start of the study and repeated 24 hours after termination of infusion . Blood sample s were obtained for the measurement of epinephrine , norepinephrine , and dopamine levels and were analyzed using high-performance liquid chromatography with electrochemical detection . Pretreatment BP measurements were significantly elevated from baseline in both groups . Fenoldopam treatment significantly reduced BP to the therapeutic goal in 8 of 8 patients ; placebo reduced BP to this goal in only 4 of 8 patients ( p < 0.05 ) . At the end of the titration period , the therapeutic goal BP was not significantly different from baseline in the fenoldopam group . HR was significantly elevated ( p < 0.05 ) at goal in the fenoldopam group as compared with the placebo group . Fenoldopam administration lowered SBP and DBP to goal in a mean time of 28 minutes versus 42.5 minutes in the placebo group . There were no significant differences in catecholamine levels at any of the measurement periods . CONCLUSION Fenoldopam is an effective drug for reducing BP following hypertensive episodes in the postoperative setting . Fenoldopam use is associated with an increase in HR versus placebo We performed the present studies to determine whether a proximal renal tubular dopamine D1-like receptor defect exists in human essential hypertension . Twenty-four subjects were studied ( 13 normotensive and 11 hypertensive ) in a r and omized , double-blind , vehicle-controlled study using fenoldopam , a selective D1-like receptor agonist . Subjects were studied in sodium metabolic balance at 300 mEq/d , after which the salt sensitivity of their blood pressure was determined . Fenoldopam at peak doses of 0.1 to 0.2 microgram/kg per minute decreased mean arterial pressure in hypertensive subjects but did not change mean pressure in normotensive subjects . Fenoldopam increased renal plasma flow to a greater extent in hypertensive than normotensive subjects . Fenoldopam increased both urinary and fractional sodium excretions in the hypertensive and normotensive groups . In normotensive but not hypertensive subjects , fenoldopam increased the fractional excretion of lithium and distal sodium delivery . In contrast , both distal fractional sodium reabsorption and sodium-potassium exchange fell significantly in hypertensive subjects . We conclude that human essential hypertension is associated with a reduction in the proximal tubular response to D1-like receptor stimulation compared with normotensive subjects . Hypertensive subjects appear to have a compensatory upregulation of renal vascular and distal tubular D1-like receptor function that offsets the proximal tubular defect , result ing in an enhanced natriuretic response to D1-like receptor stimulation We studied the renal effects of intravenous administration of fenoldopam mesylate , a dopamine-1 agonist , vs sodium nitroprusside following acute reduction of blood pressure ( BP ) in 11 patients with severe hypertension ( supine BP , 168/124 to 252/135 mm Hg ) . Following r and omization ( open-label ) , timed urinary and plasma sample s for clearance of urea and creatinine and excretion of sodium , potassium , and calcium were obtained as well as plasma renin activity for a two-hour collection prior to infusion , during a two-hour period of BP control ( supine diastolic BP , 95 to 110 mm Hg ) , and following two hours off the drugs . Mean arterial pressure was lowered similarly with the two drugs ( -22 % on fenoldopam vs -20 % on nitroprusside ; P = NS ) , and neither plasma renin activity nor plasma aldosterone concentration were changed by either drug . However , patients receiving fenoldopam had significant increases in urinary flow and excretion of sodium , potassium , and calcium , whereas patients receiving nitroprusside had no changes in these parameters . Patients receiving fenoldopam had a net fluid balance of -334 mL from the end of baseline to the end of the treatment period , while the nitroprusside group had a positive balance of 382 mL. Thus , these findings show that acute BP reduction with fenoldopam is associated with both a diuresis and natriuresis in severely hypertensive patients while lowering BP with nitroprusside does not predictably alter renal function and causes a moderate expansion in volume Eighteen patients with New York Heart Association class III congestive heart failure were given single 100 mg oral doses of fenoldopam with food or fasting in a r and om‐order single‐blind crossover trial . Before and after each fenoldopam dose , thermodilution cardiac output , right atrial pressure , pulmonary artery pressure , and pulmonary capillary wedge pressure ( PCWP ) were measured with a balloon‐tipped pulmonary artery catheter , and heart rates and blood pressures were recorded with an automated sphyg‐momanometer . Compared with fasting , bioavailability of fenoldopam was decreased significantly when administered with food : mean peak plasma fenoldopam level decreased from 26.5 ( ±4.1 SEM ) ng/ml to 10.9 ( ±1.7 SEM ) ng/ml ( p = 0.0004 ) and mean area under the concentration‐time curve was decreased from 44.7 ( ±5.8 SEM ) ng · hr/ml to 26.8 ( ±4.1 SEM ) ng · hr/ml ( p = 0.0001 ) . Fenoldopam administration to fasting patients result ed in decreases in mean arterial pressure , systemic vascular resistance , and PCWP and significant increases in cardiac index without change in heart rate . The maximum changes in mean cardiac index , systemic vascular resistance , and PCWP were greatest 1 hour after oral administration and did not persist beyond 3 hours after administration . In fasting patients , changes in cardiac index were correlated with plasma fenoldopam levels , whereas changes in PCWP and mean arterial pressure did not correlate significantly with the observed fenoldopam level |
763 | 26,858,214 | Verbal learning and memory and attention are most consistently impaired by acute and chronic exposure to cannabis .
Psychomotor function is most affected during acute intoxication , with some evidence for persistence in chronic users and after cessation of use .
Associations between poorer performance and a range of cannabis use parameters , including a younger age of onset , are frequently reported .
Little further evidence has emerged for the development of tolerance to the acutely impairing effects of cannabis . | Cannabis use has been associated with impaired cognition during acute intoxication as well as in the unintoxicated state in long-term users .
However , the evidence has been mixed and contested , and no systematic review s of the literature on neuropsychological task-based measures of cognition have been conducted in an attempt to synthesize the findings . | OBJECTIVE This study aim ed to evaluate the abuse potential and cognitive effects of nabiximols ( Sativex , GW Pharma Ltd. Salisbury , UK ) , an oromucosal spray primarily containing delta‐9‐tetrahydrocannabinol ( THC ) and cannabidiol ( CBD ) . METHODS This was a single‐dose , r and omized , double‐blind , crossover study comparing nabiximols ( 4 , 8 , and 16 consecutive sprays : 10.8 , 21.6 , and 43.2 mg THC , respectively ) with dronabinol 20 and 40 mg ( synthetic THC : Marinol , Solvay Pharmaceuticals , Brussels , Belgium ) and matching placebos in 23 recreational cannabis users . Subjective and cognitive/psychomotor measures were administered over 24 h post‐dose . RESULTS Dronabinol was significantly different from placebo on abuse potential measures , thereby confirming study validity . Nabiximols 10.8 mg was not significantly different from placebo on primary measures but was different on some secondary measures . Nabiximols 21.6 mg was significantly greater than placebo on some primary / secondary measures , whereas nabiximols 43.2 mg showed significant effects on most measures . Nabiximols 10.8 mg was significantly lower than dronabinol doses on most measures ( p < 0.05 ) . Dronabinol 20 mg effects were numerically higher than nabiximols 21.6 mg but were statistically significant only for some measures . Dronabinol 40 mg and nabiximols 43.2 mg were generally not statistically different . CONCLUSIONS Both dronabinol and nabiximols had significant abuse potential compared with placebo at higher doses . Nabiximols showed similar or slightly less abuse potential compared with dronabinol . Therefore , the abuse potential of nabiximols should be no higher than that of dronabinol BACKGROUND Our previous research suggested the involvement of γ-aminobutyric acid ( GABA ) , in particular the GABAB receptor subtype , in the interoceptive effects of Δ(9)-tetrahydrocannabinol ( Δ(9)-THC ) . The aim of the present study was to determine the potential involvement of the GABAA receptor subtype by assessing the separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ(9)-THC using pharmacologically selective drug-discrimination procedures . METHODS Ten cannabis users learned to discriminate 30 mg oral Δ(9)-THC from placebo and then received diazepam ( 5 and 10 mg ) , Δ(9)-THC ( 5 , 15 and 30 mg ) and placebo , alone and in combination . Self-report , task performance and physiological measures were also collected . RESULTS Δ(9)-THC functioned as a discriminative stimulus , produced subjective effects typically associated with cannabinoids ( e.g. , High , Stoned , Like Drug ) and elevated heart rate . Diazepam alone impaired performance on psychomotor performance tasks and increased ratings on a limited number of self-report question naire items ( e.g. , Any Effect , Se date d ) , but did not substitute for the Δ(9)-THC discriminative stimulus or alter the Δ(9)-THC discrimination dose-response function . Similarly , diazepam had limited impact on the other behavioral effects of Δ(9)-THC . CONCLUSIONS These results suggest that the GABAA receptor subtype has minimal involvement in the interoceptive effects of Δ(9)-THC , and by extension cannabis , in humans Rationale Long-term heavy cannabis use can result in memory impairment . Adolescent users may be especially vulnerable to the adverse neurocognitive effects of cannabis . Objectives and methods In a cross-sectional and prospect i ve neuropsychological study of 181 adolescents aged 16–20 ( mean 18.3 years ) , we compared performance indices from one of the most widely used measures of learning and memory — the Rey Auditory Verbal Learning Test — between cannabis users ( n = 52 ; mean 2.4 years of use , 14 days/month , median abstinence 20.3 h ) , alcohol users ( n = 67 ) and non-user controls ( n = 62 ) matched for age , education and premorbid intellectual ability ( assessed prospect ively ) , and alcohol consumption for cannabis and alcohol users . Results Cannabis users performed significantly worse than alcohol users and non-users on all performance indices . They recalled significantly fewer words overall ( p < 0.001 ) , demonstrating impaired learning ( p < 0.001 ) , retention ( p < 0.001 ) and retrieval ( p < 0.05 ) ( Cohen ’s d 0.43–0.84 ) . The degree of impairment was associated with the duration , quantity , frequency and age of onset of cannabis use , but was unrelated to alcohol exposure or other drug use . No gender effects were detected and the findings remained after controlling for premorbid intellectual ability . An earlier age of onset of regular cannabis use was associated with worse memory performance after controlling for extent of exposure to cannabis . Conclusions Despite relatively brief exposure , adolescent cannabis users relative to their age-matched counterparts demonstrated similar memory deficits to those reported in adult long-term heavy users . The results indicate that cannabis adversely affects the developing brain and reinforce concerns regarding the impact of early exposure Recent reports show that fewer adolescents believe that regular cannabis use is harmful to health . Concomitantly , adolescents are initiating cannabis use at younger ages , and more adolescents are using cannabis on a daily basis . The purpose of the present study was to test the association between persistent cannabis use and neuropsychological decline and determine whether decline is concentrated among adolescent-onset cannabis users . Participants were members of the Dunedin Study , a prospect i ve study of a birth cohort of 1,037 individuals followed from birth ( 1972/1973 ) to age 38 y. Cannabis use was ascertained in interviews at ages 18 , 21 , 26 , 32 , and 38 y. Neuropsychological testing was conducted at age 13 y , before initiation of cannabis use , and again at age 38 y , after a pattern of persistent cannabis use had developed . Persistent cannabis use was associated with neuropsychological decline broadly across domains of functioning , even after controlling for years of education . Informants also reported noticing more cognitive problems for persistent cannabis users . Impairment was concentrated among adolescent-onset cannabis users , with more persistent use associated with greater decline . Further , cessation of cannabis use did not fully restore neuropsychological functioning among adolescent-onset cannabis users . Findings are suggestive of a neurotoxic effect of cannabis on the adolescent brain and highlight the importance of prevention and policy efforts targeting adolescents Worldwide cannabis dependence is increasing , as is the concentration of Δ9-tetrahydrocannabinol ( THC ) in street cannabis . At the same time , the concentration of the second most abundant cannabinoid in street cannabis , cannabidiol ( CBD ) , is decreasing . These two cannabinoids have opposing effects both pharmacologically and behaviorally when administered in the laboratory . No research has yet examined how the ratio of these constituents impacts on the appetitive/reinforcing effects of cannabis in humans . A total of 94 cannabis users were tested 7 days apart , once while non-intoxicated and once while acutely under the influence of their own chosen smoked cannabis on dependence-related measures . Using an unprecedented methodology , a sample of cannabis ( as well as saliva ) was collected from each user and analyzed for levels of cannabinoids . On the basis of CBD : THC ratios in the cannabis , individuals from the top and bottom tertiles were directly compared on indices of the reinforcing effects of drugs , explicit liking , and implicit attentional bias to drug stimuli . When intoxicated , smokers of high CBD : THC strains showed reduced attentional bias to drug and food stimuli compared with smokers of low CBD : THC . Those smoking higher CBD : THC strains also showed lower self-rated liking of cannabis stimuli on both test days . Our findings suggest that CBD has potential as a treatment for cannabis dependence . The acute modulation of the incentive salience of drug cues by CBD may possibly generalize to a treatment for other addictive disorders Introduction Cannabinoids produce a spectrum of effects in humans including euphoria , cognitive impairments , psychotomimetic effects , and perceptual alterations . The extent to which dopaminergic systems contribute to the effects of Δ-9-tetrahydrocannabinol ( Δ-9-THC ) remains unclear . This study evaluated whether pretreatment with a dopamine receptor antagonist altered the effects of Δ-9-THC in humans . Material s and methods In a 2-test-day double-blind study , 28 subjects including healthy subjects ( n = 17 ) and frequent users of cannabis ( n = 11 ) were administered active ( 0.057 mg/kg ) or placebo oral haloperidol in r and om order followed 90 and 215 min later by fixed order intravenous administration of placebo ( vehicle ) and active ( 0.0286 mg/kg ) Δ-9-THC , respectively . Results Consistent with previous reports , intravenous Δ-9-THC produced psychotomimetic effects , perceptual alterations , and subjective effects including “ high . ” Δ-9-THC also impaired verbal recall and attention . Haloperidol pretreatment did not reduce any of the behavioral effects of Δ-9-THC . Haloperidol worsened the immediate free and delayed free and cued recall deficits produced by Δ-9-THC . Haloperidol and Δ-9-THC worsened distractibility and vigilance . Neither drug impaired performance on a motor screening task , the Stockings of Cambridge task , or the delayed match to sample task . Frequent users had lower baseline plasma prolactin levels and blunted Δ-9-THC induced memory impairments . Conclusions The deleterious effects of haloperidol pretreatment on the cognitive effects of Δ-9-THC are consistent with the pre clinical literature in suggesting crosstalk between DAergic and CBergic systems . However , it is unlikely that DA D2 receptor mechanisms play a major role in mediating the psychotomimetic and perceptual altering effects of Δ-9-THC . Further investigation is warranted to underst and the basis of the psychotomimetic effects of Δ-9-THC and to better underst and the crosstalk between DAergic and CBergic systems Rationale Δ9-Tetrahydrocannabinol ( THC ) is the main active constituent of cannabis . In recent years , the average THC content of some cannabis cigarettes has increased up to approximately 60 mg per cigarette ( 20 % THC cigarettes ) . Acute cognitive and psychomotor effects of THC among recreational users after smoking cannabis cigarettes containing such high doses are unknown . Objectives The objective of this study was to study the dose – effect relationship between the THC dose contained in cannabis cigarettes and cognitive and psychomotor effects for THC doses up to 69.4 mg ( 23 % ) . Material s and methods This double-blind , placebo-controlled , r and omised , four-way cross-over study included 24 non-daily male cannabis users ( two to nine cannabis cigarettes per month ) . Participants smoked four cannabis cigarettes containing 0 , 29.3 , 49.1 and 69.4 mg THC on four exposure days . Results The THC dose in smoked cannabis was linearly associated with a slower response time in all tasks ( simple reaction time , visuo-spatial selective attention , sustained attention , divided attention and short-term memory tasks ) and motor control impairment in the motor control task . The number of errors increased significantly with increasing doses in the short-term memory and the sustained attention tasks . Some participants showed no impairment in motor control even at THC serum concentrations higher than 40 ng/mL. High feeling and drowsiness differed significantly between treatments . Conclusions Response time slowed down and motor control worsened , both linearly , with increasing THC doses . Consequently , cannabis with high THC concentrations may be a concern for public health and safety if cannabis smokers are unable to titrate to a high feeling corresponding to a desired plasma THC level While the effects of cannabis use on retrospective memory have been extensively examined , only a limited number of studies have focused on the links between cannabis use and prospect i ve memory . We conducted two studies to examine the links between cannabis use and both time-based and event-based prospect i ve memory as well as potential mechanisms underlying these links . For the first study , 805 students completed an online survey design ed to assess cannabis consumption , problems with cannabis use indicative of a disorder , and frequency of experiencing prospect i ve memory failures . The results showed small to moderate sized correlations between cannabis consumption , problems with cannabis use , and prospect i ve memory . However , a series of mediation analyses revealed that correlations between problems with cannabis use and prospect i ve memory were driven by self-reported problems with retrospective memory . For the second study , 48 non-users ( who had never used cannabis ) , 48 experimenters ( who had used cannabis five or fewer times in their lives ) , and 48 chronic users ( who had used cannabis at least three times a week for one year ) were administered three objective prospect i ve memory tests and three self-report measures of prospect i ve memory . The results revealed no objective deficits in prospect i ve memory associated with chronic cannabis use . In contrast , chronic cannabis users reported experiencing more internally-cued prospect i ve memory failures . Subsequent analyses revealed that this effect was driven by self-reported problems with retrospective memory as well as by use of alcohol and other drugs . Although our sample s were not fully characterized with respect to variables such as neurological disorders and family history of substance use disorders , leaving open the possibility that these variables may play a role in the detected relationships , the present findings indicate that cannabis use has a modest effect on self-reported problems with prospect i ve memory , with a primary problem with retrospective memory appearing to underlie this relationship The relationships between executive processes , associative learning and different aspects of real world memory functioning were explored in a sample of cannabis users and nonusers . Measures of executive component processes , associative learning , everyday memory , prospect i ve memory , and cognitive failures were administered . Relative to nonusers , cannabis users were found to be impaired in several aspects of real world memory functioning . No other group differences were apparent . The absence of cannabis related deficits in those executive component processes and aspects of learning that are believed to support real world memory processes is surprising given that cannabis related deficits were obtained in real world memory . The present results are discussed within the context of neuroimaging evidence which suggests that cannabis users may exhibit different patterns of neural activation when performing executive tasks while not always exhibiting deficits on these tasks Rationale One of the most often reported cognitive deficits of acute cannabis administration is an impaired recall of previously learned information . Objective The aim of the present study was to determine whether cannabis-induced memory impairment in humans is mediated via glutamatergic or cholinergic pathways . Methods Fifteen occasional cannabis users participated in a double-blind , placebo-controlled , six-way cross-over study . On separate test days , subjects received combinations of pretreatment ( placebo , vardenafil 20 mg or rivastigmine 3 mg ) and treatment ( placebo or 1,376 mg cannabis/kg body weight ) . Cognitive tests were administered immediately after inhalation of treatment was finished and included measures of memory ( visual verbal learning task , prospect i ve memory test , Sternberg memory test ) , perceptual-motor control ( critical tracking task ) , attention ( divided attention task ) and motor impulsivity ( stop signal task ) . Results The results of this study demonstrate that subjects under the influence of cannabis were impaired in all memory tasks , in critical tracking , divided attention and the stop signal task . Pretreatment with rivastigmine attenuated the effect of cannabis on delayed recall and showed a trend towards significance on immediate recall . When cannabis was given in combination with vardenafil , there were no significant interaction effects in any of the tasks . Conclusions The present data therefore suggest that acetylcholine plays an important role in cannabis-induced memory impairment , whereas similar results for glutamate have not been demonstrated in this study Community-based studies suggest that cannabis products that are high in Δ9-tetrahydrocannabinol ( THC ) but low in cannabidiol ( CBD ) are particularly hazardous for mental health . Laboratory-based studies are ideal for clarifying this issue because THC and CBD can be administered in pure form , under controlled conditions . In a between-subjects design , we tested the hypothesis that pre-treatment with CBD inhibited THC-elicited psychosis and cognitive impairment . Healthy participants were r and omised to receive oral CBD 600 mg ( n=22 ) or placebo ( n=26 ) , 210 min ahead of intravenous ( IV ) THC ( 1.5 mg ) . Post-THC , there were lower PANSS positive scores in the CBD group , but this did not reach statistical significance . However , clinical ly significant positive psychotic symptoms ( defined a priori as increases ≥3 points ) were less likely in the CBD group compared with the placebo group , odds ratio (OR)=0.22 ( χ2=4.74 , p<0.05 ) . In agreement , post-THC paranoia , as rated with the State Social Paranoia Scale ( SSPS ) , was less in the CBD group compared with the placebo group ( t=2.28 , p<0.05 ) . Episodic memory , indexed by scores on the Hopkins Verbal Learning Task-revised ( HVLT-R ) , was poorer , relative to baseline , in the placebo pre-treated group ( -10.6±18.9 % ) compared with the CBD group ( -0.4%±9.7 % ) ( t=2.39 , p<0.05 ) . These findings support the idea that high-THC/low-CBD cannabis products are associated with increased risks for mental health Background The present study assessed psychomotor function in chronic , daily cannabis smokers during 3 weeks continuously monitored abstinence on a secure research unit . We hypothesized that psychomotor performance would improve during abstinence of chronic , daily cannabis smokers . Methodology /Principal Findings Performance on the critical tracking ( CTT ) and divided attention ( DAT ) tasks was assessed in 19 male chronic , daily cannabis smokers at baseline and after 8 , 14–16 and 21–23 days of continuously monitored abstinence . Psychomotor performance was compared to a control group of non-intoxicated occasional drug users . Critical frequency ( λc ) of the CTT and tracking error and control losses of the DAT were the primary outcome measures . Results showed that chronic cannabis smokers ’ performance on the CTT ( p<0.001 ) and the DAT ( p<0.001 ) was impaired during baseline relative to the comparison group . Psychomotor performance in the chronic cannabis smokers improved over 3 weeks of abstinence , but did not recover to equivalent control group performance . Conclusions / Significance Sustained cannabis abstinence moderately improved critical tracking and divided attention performance in chronic , daily cannabis smokers , but impairment was still observable compared to controls after 3 weeks of abstinence . Between group differences , however , need to be interpreted with caution as chronic smokers and controls were not matched for education , social economic status , life style and race Previous studies have established a relationship between marijuana use and risky behavior in natural setting s. A limited number of laboratory investigations of marijuana effects on human risk taking have been conducted . The present study was design ed to examine the acute effects of smoked marijuana on human risk taking , and to identify behavioral mechanisms that may be involved in drug-induced changes in the probability of risky behavior . Using a laboratory measure of risk taking design ed to address acute drug effects , 10 adults were administered placebo cigarettes and three doses of active marijuana cigarettes ( half placebo and half 1.77 % ; 1.77 % ; and 3.58 % Δ9-THC ) in a within-subject repeated- measures experimental design . The risk-taking task presented subjects with a choice between two response options operationally defined as risky and nonrisky . Data analyses examined cardiovascular and subjective effects , response rates , distribution of choices between the risky and nonrisky option , and first-order transition probabilities of trial-by-trial data . The 3.58 % THC dose increased selection of the risky response option , and uniquely shifted response probabilities following both winning and losing outcomes following selection of the risky option . Acute marijuana administration thereby produced measurable changes in risky decision making under laboratory conditions . Consistent with previous risk-taking studies , shifts in trial-by-trial response probabilities at the highest dose suggested a change in sensitivity to both reinforced and losing risky outcomes . Altered sensitivity to consequences may be a mechanism in drug-induced changes in risk taking . Possible neurobiological sites of action related to THC are discussed Recent advances in the underst and ing of brain cannabinoid receptor function have renewed interest in the association between cannabinoid compounds and psychosis . In a 3-day , double-blind , r and omized , and counterbalanced study , the behavioral , cognitive , and endocrine effects of 0 , 2.5 , and 5 mg intravenous delta-9-tetrahydrocannabinol ( Δ-9-THC ) were characterized in 22 healthy individuals , who had been exposed to cannabis but had never been diagnosed with a cannabis abuse disorder . Prospect i ve safety data at 1 , 3 , and 6 months post study was also collected . Δ-9-THC ( 1 ) produced schizophrenia-like positive and negative symptoms ; ( 2 ) altered perception ; ( 3 ) increased anxiety ; ( 4 ) produced euphoria ; ( 5 ) disrupted immediate and delayed word recall , sparing recognition recall ; ( 6 ) impaired performance on tests of distractibility , verbal fluency , and working memory ( 7 ) did not impair orientation ; ( 8) increased plasma cortisol . These data indicate that Δ-9-THC produces a broad range of transient symptoms , behaviors , and cognitive deficits in healthy individuals that resemble some aspects of endogenous psychoses . These data warrant further study of whether brain cannabinoid receptor function contributes to the pathophysiology of psychotic disorders Rationale Cannabinoids have been shown to alter time perception , but existing literature has several limitations . Few studies have included both time estimation and production tasks , few control for subvocal counting , most had small sample sizes , some did not record subjects ’ cannabis use , many tested only one dose , and used either oral or inhaled administration of Δ9-tetrahydrocannabinol ( THC ) , leading to variable pharmacokinetics , and some used whole-plant cannabis containing cannabinoids other than THC . Our study attempted to address these limitations . Objectives This study aims to characterize the acute effects of THC and frequent cannabis use on seconds-range time perception . THC was hypothesized to produce transient , dose-related time overestimation and underproduction . Frequent cannabis smokers were hypothesized to show blunted responses to these alterations . Methods IV THC was administered at doses from 0.015 to 0.05 mg/kg to 44 subjects who participated in several double-blind , r and omized , counterbalanced , crossover , placebo-controlled studies . Visual time estimation and production tasks in the seconds range were presented to subjects three times on each test day . Results All doses induced time overestimation and underproduction . Chronic cannabis use had no effect on baseline time perception . While infrequent/nonsmokers showed temporal overestimation at medium and high doses and temporal underproduction at all doses , frequent cannabis users showed no differences . THC effects on time perception were not dose related . Conclusions A psychoactive dose of THC increases internal clock speed as indicated by time overestimation and underproduction . This effect is not dose related and is blunted in chronic cannabis smokers who did not otherwise have altered baseline time perception Although a wealth of pre clinical evidence indicates an interplay between the μ-opioid ( MOR ) and cannabinoid 1 receptor ( CB1R ) systems , the precise nature of the cross modulation in humans is unclear . The objective of this study was to evaluate the effects of pretreatment with the MOR antagonist , naltrexone , on the subjective , behavioural and cognitive effects of the CB1R agonist , Δ9-tetrahydrocannabinol ( THC ) , in healthy human subjects . Healthy human subjects , screened carefully for any medical or psychiatric illness , were administered either placebo or active naltrexone ( 25 mg ) orally on each test day , followed 45 min later by placebo and 165 min later by active i.v . THC ( 0.025 mg/kg ) in a r and omized , fixed-order , double-blind manner . Subjective , behavioural and cognitive effects were assessed before and at several points after each drug administration . THC produced expected effects , including euphoria , anxiety , transient perceptual alterations , transient psychotomimetic effects and cognitive impairments . However , naltrexone did not produce any effects alone , nor did it attenuate any of THC 's effects . Thus , in healthy human subjects who use cannabis intermittently , MOR antagonism does not modulate the common acute subjective , behavioural and cognitive effects of THC Human performance studies have usually relied on low-potency marijuana ( 4 % THC ) for determining THC-induced impairment . The present study was design ed to assess the effects of high-potency marijuana ( 13 % THC ) on human performance . In all , 20 recreational users of marijuana participated in a double-blind , placebo controlled , three way cross-over study . The treatments consisted of single doses of 0 , 250 , and 500 μg/kg THC . Performance tests were conducted at regular intervals between 15 min and 6 h postsmoking and included measures of motor control ( Critical tracking task ) , executive function ( Tower of London ) motor impulsivity ( Stop signal task ) , and risk taking ( Iowa gambling task ) . THC significantly impaired performance in the Critical tracking task and decreased the number of correct decisions in the Tower of London task . In addition , THC significantly increased stop reaction time and the proportions of commission and omission errors in the Stop signal task . THC-induced impairments lasted up to 6 h postsmoking as indicated by the absence of a THC × Time after smoking interaction . Effect sizes for performance impairments produced by THC 250 μg/kg were relatively low but generally increased by a factor of two in case of THC 500 μg/kg . These data suggest that high potency marijuana consistently impairs executive function and motor control . Use of higher doses of THC in controlled studies may offer a reliable indication of THC induced impairment as compared to lower doses of THC that have traditionally been used in performance studies Paranoia is receiving increasing attention in its own right , since it is a central experience of psychotic disorders and a marker of the health of a society . Paranoia is associated with use of the most commonly taken illicit drug , cannabis . The objective was to determine whether the principal psychoactive ingredient of cannabis—∆9-tetrahydrocannabinol (THC)—causes paranoia and to use the drug as a probe to identify key cognitive mechanisms underlying paranoia . A r and omized , placebo-controlled , between-groups test of the effects of intravenous THC was conducted . A total of 121 individuals with paranoid ideation were r and omized to receive placebo , THC , or THC preceded by a cognitive awareness condition . Paranoia was assessed extensively via a real social situation , an immersive virtual reality experiment , and st and ard self-report and interviewer measures . Putative causal factors were assessed . Principal components analysis was used to create a composite paranoia score and composite causal variables to be tested in a mediation analysis . THC significantly increased paranoia , negative affect ( anxiety , worry , depression , negative thoughts about the self ) , and a range of anomalous experiences , and reduced working memory capacity . The increase in negative affect and in anomalous experiences fully accounted for the increase in paranoia . Working memory changes did not lead to paranoia . Making participants aware of the effects of THC had little impact . In this largest study of intravenous THC , it was definitively demonstrated that the drug triggers paranoid thoughts in vulnerable individuals . The most likely mechanism of action causing paranoia was the generation of negative affect and anomalous experiences Rationale Marijuana is believed to increase impulsivity and risk taking , but the processes whereby it affects such behaviors are not understood . Indeed , either the pharmacologic effect of delta-9-tetrahydrocannabinol ( THC ) or the expectancy of receiving it may lead to deficits in cognitive processing and increases in risk taking . Objectives and methods We examined the relative effects of expecting to receive active marijuana and the pharmacological drug effects using a balanced placebo design . Young adult regular marijuana users ( N = 136 ) were r and omly assigned into one of four groups in a two × two instructional set ( Told THC vs. Told no THC ) by drug administration ( smoked marijuana with 2.8 % THC vs. placebo ) design . Dependent measures included subjective intoxication , behavioral impulsivity , and decision-making related to risky behaviors . Results Active THC , regardless of expectancy , impaired inhibition on the Stop Signal and Stroop Color-Word tasks . Expectancy of having smoked THC , regardless of active drug , decreased impulsive decision-making on a delay discounting task among participants reporting no deception and increased perception of sexual risk among women , consistent with a compensatory effect . Expectancy of smoking THC in combination with active THC increased negative perceptions from risky alcohol use . Active drug and expectancy independently increased subjective intoxication . Conclusions Results highlight the importance of marijuana expectancy effects as users believing they are smoking marijuana may compensate for expected intoxication effects when engaged in deliberate decision-making by making less impulsive and risky decisions . Effects of marijuana on impulsive disinhibition , by contrast , reflect direct pharmacologic effects for which participants did not compensate INTRODUCTION The medical use of cannabinoids is limited mainly by their undesirable effects . With respect to acute psychotropic effects , the aim of this study is the comparison of an oral cannabis extract and low-dose diazepam in a cross-over experiment in drug-naïve healthy women . METHODS Sixteen healthy females participated in this r and omized , double-blind , active comparator-controlled , single-dose , balanced 2-way cross-over study . Cannabis extract with st and ardised Delta (9)-tetrahydrocannabinol ( THC ) content ( 20 mg ) or active placebo ( 5 mg diazepam ) was administered orally . Subjects were assessed by self- and observer-rated visual analogue scales ( VAS ) , the BRIEF PSYCHIATRIC RATING SCALE ( BPRS ) and three psychomotor tests up to 6 h after administration . RESULTS VAS showed significantly elevated fatigue , drowsiness , dizziness , and " feeling high " after cannabis as compared to baseline and diazepam . BPRS scores were significantly higher after cannabis intake . Only in one psychomotor test a decrease of psychomotor activity after cannabis was evident . One subject in the cannabis condition experienced severe transient psychotic symptoms . DISCUSSION Orally administered cannabis produced significant central depressant side-effects compared to diazepam , mostly subjective effects ( VAS ) but marginal effects in psychomotor performance in 15 healthy females . Regarding the medical use of cannabis , a rigorous benefit-risk analysis and an exact psychiatric assessment before and during treatment are necessary OBJECTIVES Few cognitive tasks are adequately sensitive to show the small decrements in performance in abstinent chronic cannabis users . In this series of three experiments we set out to demonstrate a variety of tasks that are sufficiently sensitive to show differences in visual memory , verbal memory , everyday memory and executive function between controls and cannabis users . METHODS A series of three studies explored cognitive function deficits in cannabis users ( phonemic verbal fluency , visual recognition and immediate and delayed recall , and prospect i ve memory ) in short-term abstinent cannabis users . Participants were selected using snowball sampling , with cannabis users being compared to a st and ard control group and a tobacco-use control group . RESULTS The cannabis users , compared to both control groups , had deficits on verbal fluency , visual recognition , delayed visual recall , and short- and long-interval prospect i ve memory . There were no differences for immediate visual recall . CONCLUSIONS These findings suggest that cannabis use leads to impaired executive function . Further research needs to explore the longer term impact of cannabis use Acute marijuana administration may alter response – reinforcer relationships via a change in reinforcer efficacy , but may also impair coordination and motor function . One approach to evaluating drug effects on both motor function and reinforcer efficacy involves fitting the matching law equation to data obtained under multiple variable interval ( VI ) schedules . The present report describes an experiment that examined the effects of acute marijuana on response properties using this approach . Six human subjects responded under a multiple VI schedule for monetary reinforcers after smoking placebo and two active doses of marijuana . The low marijuana dose produced un systematic changes in responding . As measured by the matching law equation parameters ( k and rB ) , at the high dose five subjects showed a decrease-motor-related properties of response rate and four subjects ' responding indicated a decrease in reinforcer efficacy . These data raise the possibility that , at high doses , marijuana administration alters both motor function and reinforcer efficacy Cannabis is one of the most widely used illicit substances and there is growing interest in the association between cannabis use and psychosis . Delta-9-Tetrahydrocannabinol ( Δ-9-THC ) the principal active ingredient of cannabis has been shown to induce psychotomimetic and amnestic effects in healthy individuals . Whether people who frequently use cannabis are either protected from or are tolerant to these effects of Δ-9-THC has not been established . In a 3-day , double-blind , r and omized , placebo-controlled study , the dose-related effects of 0 , 2.5 , and 5 mg intravenous Δ-9-THC were studied in 30 frequent users of cannabis and compared to 22 healthy controls . Δ-9-THC ( 1 ) produced transient psychotomimetic effects and perceptual alterations ; ( 2 ) impaired memory and attention ; ( 3 ) increased subjective effects of ‘ high ’ ; ( 4 ) produced tachycardia ; and ( 5 ) increased serum cortisol in both groups . However , relative to controls , frequent users showed blunted responses to the psychotomimetic , perceptual altering , cognitive impairing , anxiogenic , and cortisol increasing effects of Δ-9-THC but not to its euphoric effects . Frequent users also had lower prolactin levels . These data suggest that frequent users of cannabis are either inherently blunted in their response to , and /or develop tolerance to the psychotomimetic , perceptual altering , amnestic , endocrine , and other effects of cannabinoids It has long been known that acute marijuana administration impairs working memory ( e.g. , the discrimination of stimuli separated by a delay ) . The determination of which of the individual components of memory are altered by marijuana is an unresolved problem . Previous human studies did not use test protocol s that allowed for the determination of delay-independent ( initial discrimination ) from delay-dependent ( forgetting or retrieval ) components of memory . Using methods developed in the experimental analysis of behavior and signal detection theory , we tested the acute effects of smoked marijuana on forgetting functions in 5 humans . Immediately after smoking placebo , a low dose , or a high dose of marijuana ( varying in delta9-THC content ) , subjects completed delayed match-to- sample testing that included a range of retention intervals within each test session ( 0.5 , 4 , 12 , and 24 s ) . Performances ( discriminability ) at each dose were plotted as forgetting functions , as described and developed by White and colleagues ( White , 1985 ; White & Ruske , 2002 ) . For all 5 subjects , both delta9-THC doses impaired delay-dependent discrimination but not delay-independent discrimination . The outcome is consistent with current nonhuman studies examining the role of the cannabinoid system on delayed matching procedures , and the data help illuminate one behavioral mechanism through which marijuana alters memory performance There are no FDA -approved pharmacotherapies for cannabis dependence . Cannabis is the most widely used illicit drug in the world , and patients seeking treatment for primary cannabis dependence represent 25 % of all substance use admissions . We conducted a phase IIa proof-of-concept pilot study to examine the safety and efficacy of a calcium channel/GABA modulating drug , gabapentin , for the treatment of cannabis dependence . A 12-week , r and omized , double-blind , placebo-controlled clinical trial was conducted in 50 unpaid treatment-seeking male and female out patients , aged 18–65 years , diagnosed with current cannabis dependence . Subjects received either gabapentin ( 1200 mg/day ) or matched placebo . Manual-guided , abstinence-oriented individual counseling was provided weekly to all participants . Cannabis use was measured by weekly urine toxicology and by self-report using the Timeline Followback Interview . Cannabis withdrawal symptoms were assessed using the Marijuana Withdrawal Checklist . Executive function was measured using subtests from the Delis – Kaplan Executive Function System . Relative to placebo , gabapentin significantly reduced cannabis use as measured both by urine toxicology ( p=0.001 ) and by the Timeline Followback Interview ( p=0.004 ) , and significantly decreased withdrawal symptoms as measured by the Marijuana Withdrawal Checklist ( p<0.001 ) . Gabapentin was also associated with significantly greater improvement in overall performance on tests of executive function ( p=0.029 ) . This POC pilot study provides preliminary support for the safety and efficacy of gabapentin for treatment of cannabis dependence that merits further study , and provides an alternative conceptual framework for treatment of addiction aim ed at restoring homeostasis in brain stress systems that are dysregulated in drug dependence and withdrawal The aim of the present study was to examine prospect i ve memory impairments associated with cannabis use in young adults . An independent measures design utilising pre-existing groups of users and non-users was employed in which an opportunity sample of 90 undergraduates study ing at universities in the north east of Engl and participated . The number of prospect i ve memory failures reported on the Prospect i ve Memory Question naire and the number of location — action combinations correctly recalled during a video-based prospect i ve memory task were measured . The number of strategies used to assist memory , level of anxiety and depression , and use of alcohol , nicotine and any other recreational drugs in addition to cannabis were also measured and controlled during the analysis . Analysis revealed no significant differences in the number of self-reported prospect i ve memory failures ; however , cannabis users recalled significantly fewer location — action combinations than non-users in the video-based prospect i ve memory task . The findings from the present study suggest that cannabis use has a detrimental effect on prospect i ve memory ability in young adults but users may not be aware of these deficits Drug users have attentional biases for drug-related stimuli , and the frequency of drug use and craving are associated with attentional bias . However , research to date has not investigated the relationship between the severity of cannabis dependence , and attentional bias for cannabis-related stimuli . In the present study , 28 recreational cannabis users completed a modified Stroop task with cannabis-related and control words , plus question naire measures of cannabis dependence and craving . Participants were split into those who met diagnostic criteria for cannabis dependence based on scores on the Cannabis Severity of Dependence Scale ( C-SDS ) , and those who did not . The cannabis-dependent group had a significant attentional bias for the cannabis-related words , but the non-dependent group did not . Correlations indicated that attentional bias was also associated with the frequency of cannabis use , and with subjective craving Abnormalities in psychomotor performance are a consistent finding in schizophrenic patients as well as in chronic cannabis users . The high levels of central cannabinoid ( CB1 ) receptors in the basal ganglia , the cerebral cortex and the cerebellum indicate their implication in the regulation of motor activity . Based on the close relationship between cannabis use , the endogenous cannabinoid system and motor disturbances found in schizophrenia , we expected that administration of cannabinoids may change pattern of psychomotor activity like in schizophrenic patients . This prospect i ve , double-blind , placebo-controlled cross-over study investigated the acute effects of cannabinoids on psychomotor performance in 24 healthy right-h and ed volunteers ( age 27.9 ± 2.9 years , 12 male ) by comparing Δ9-tetrahydrocannabinol ( Δ9-THC ) and st and ardized cannabis extract containing Δ9-THC and cannabidiol . Psychomotor performance was assessed by using a finger tapping test series . Cannabis extract , but not Δ9-THC , revealed a significant reduction of right-h and tapping frequencies that was also found in schizophrenia . As to the pure Δ9-THC condition , left-h and tapping frequencies were correlated with the plasma concentrations of the Δ9-THC metabolite 11-OH-THC . These effects are thought to be related to cannabinoid actions on CB1 receptors in the basal ganglia , the cerebral cortex and the cerebellum . Our data further demonstrate that acute CB1 receptor activation under the cannabis extract condition may also affect intermanual coordination ( IMC ) as an index of interhemispheric transfer . AIR-Scale scores as a measure of subjective perception of intoxication were dose-dependently related to IMC which was shown by an inverted U-curve . This result may be due to functional changes involving GABAergic and glutamatergic neurotransmission within the corpus callosum Heavy use of marijuana is cl aim ed to damage critical skills related to short-term memory , visual scanning and attention . Motor skills and driving safety may be compromised by the acute effects of marijuana . The aim of this study was to investigate the acute effects of 13 mg and 17 mg Δ 9-tetrahydrocannabinol ( THC ) on skills important for coordinated movement and driving and on subjective and autonomic measures in regular users of marijuana . Fourteen regular users of marijuana were enrolled . Each subject was tested on two separate days . On each test day , subjects smoked two low-nicotine cigarettes , one with and the other without THC . Seventeen mg THC was included in the cigarette on one test day and 13 mg on the other day . The sequence of cigarette types was unknown to the subject . During smoking , heart rate and blood pressure were monitored , and the subjects performed a virtual reality maze task requiring attention and motor coordination , followed by 3 other cognitive tasks ( Wisconsin Card Sorting Test ( WCST ) , a “ gambling ” task and estimation of time and distance from an approaching car ) . After smoking a cigarette with 17 mg THC , regular marijuana users hit the walls more often on the virtual maze task than after smoking cigarettes without THC ; this effect was not seen in patients after they smoked cigarettes with 13 mg THC . Performance in the WCST was affected with 17 mg THC and to a lesser extent with the use of 13 mg THC . Decision making in the gambling task was affected after smoking cigarettes with 17 mg THC , but not with 13 m THC . Smoking cigarettes with 13 and 17 mg THC increased subjective ratings of pleasure and satisfaction , drug “ effect ” and drug “ high ” . These findings imply that smoking of 17 mg THC results in impairment of cognitive — motor skills that could be important for coordinated movemen and driving , whereas the lower dose of 13 mg THC appears to cause less impairment of such skills in regular users of marijuana BACKGROUND Prior studies have separately examined the effects of dronabinol ( oral THC ) on cannabis withdrawal , cognitive performance , and the acute effects of smoked cannabis . A single study examining these clinical ly relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders . METHODS Thirteen daily cannabis smokers completed a within-subject crossover study and received 0 , 30 , 60 and 120 mg dronabinol per day for 5 consecutive days . Vital signs and subjective ratings of cannabis withdrawal , craving and sleep were obtained daily ; outcomes under active dose conditions were compared to those obtained under placebo dosing . On the 5th day of medication maintenance , participants completed a comprehensive cognitive performance battery and then smoked five puffs of cannabis for subjective effects evaluation . Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad libitum cannabis use . RESULTS Dronabinol dose-dependently attenuated cannabis withdrawal and result ed in few adverse side effects or decrements in cognitive performance . Surprisingly , dronabinol did not alter the subjective effects of smoked cannabis , but cannabis-induced increases in heart rate were attenuated by the 60 and 120 mg doses . CONCLUSIONS Dronabinol 's ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use . The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg/day . Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment , using an exp and ed range of doses , is warranted The impact of regular marijuana use on executive cognitive abilities , including decision making , is not well understood . While cross-sectional studies have suggested that substance abusers exhibit impaired decision making , as assessed by the Iowa Gambling Task , the direct role of marijuana use in the Gambling Task performance of marijuana smokers has not been well defined . In this report , we present data on performance on a modified Gambling Task in experienced marijuana users after they had smoked marijuana under controlled laboratory conditions . A total of 36 marijuana users , who reported smoking approximately 24 marijuana cigarettes per week , completed this 3-session outpatient study . During each session , these volunteers completed the Gambling Task once at baseline and 3 times after smoking a single marijuana cigarette ( 0.0 , 1.8 , or 3.9 % Δ9-THC ) . Marijuana cigarettes were administered in a double-blind fashion , and the sequence of Δ9-THC concentration was balanced across volunteers . Marijuana increased the time required to complete the task . However , advantageous card selection and money earned on the task were not disrupted by marijuana . These data are consistent with previous findings that indicated that speed of performance on tests of executive function , but not accuracy , is disrupted in experienced marijuana users during marijuana intoxication Papers pp 1195 , 1199 The strongest evidence that cannabis use may be a risk factor for later psychosis comes from a Swedish cohort study which found that heavy cannabis use at age 18 increased the risk of later schizophrenia sixfold . 1 2 This study could not establish whether adolescent cannabis use was a consequence of pre-existing psychotic symptoms rather than a cause . We present the first prospect i ve longitudinal study of adolescent cannabis use as a risk factor for adult schizophreniform disorder , taking into account childhood psychotic symptoms3 antedating cannabis use . View this table : Association between cannabis use in adolescence and schizophrenia and depressive symptoms and disorders at age 26 ( n=759 ) , controlling for childhood psychotic symptoms and use of other drugs in adolescence The Dunedin multidisciplinary health and development study ( a study of a general population birth cohort of 1037 individuals born in Dunedin , New Zeal and , in 1972 - 3)4 has a 96 % follow up rate at age 26 . It obtained information on psychotic symptoms at age 11 and drug use at ages 15 and 18 from self reports and assessed This was a double-blind , r and omised , placebo-controlled , crossover study of the acute cognitive and subjective effects of nabilone 1—3 mg in healthy male volunteers . The Cognitive Drug Research computerised system ( CDR system ) was used to assess changes in attention , working and episodic memory . In addition , a number of self-ratings were conducted including those of mood , alertness and perceived drug effects . Impairments to attention , working and episodic memory and self-ratings of alertness were evident . Volunteers also experienced a number of subjective drug effects . These data demonstrate that acute doses of nabilone in the range 1—3 mg produce clear cognitive and subjective effects in healthy volunteers , and therefore they may be used as reference data in the future study of peripherally acting cannabinoids believed to be free from such effects Introduction Taranabant is a cannabinoid 1 receptor inverse agonist that was in development for treatment of obesity . Because of central nervous system effects , the study was performed to assess the abuse potential and cognitive effects of taranabant in recreational polydrug users compared with phentermine , dronabinol , and placebo . Methods Stimulant- and cannabis-experienced polydrug users ( N = 30 ) were r and omized in a double-blind crossover study to receive taranabant 2 , 4 , 10 , and 20 mg ; phentermine 45 and 90 mg ; dronabinol 20 mg ; and placebo . Subjective and neurocognitive measures were administered for 24 hours , and peak/peak change from baseline effects were analyzed using a linear mixed-effects model . Results Phentermine 45 and 90 mg showed abuse-related subjective effects versus placebo , including drug liking , overall drug liking , and other positive/stimulant effects , whereas dronabinol 20 mg showed abuse-related positive , cannabis-like , and sedative effects . Taranabant was not significantly different from placebo on most of the subjective measures other than negative/dysphoric effects at the highest dose , and its effects were significantly less pronounced relative to phentermine and dronabinol on most measures . Phentermine improved cognitive/motor performance and dronabinol impaired motor/cognitive performance on some measures , whereas taranabant 4 and 20 mg had minor impairment effects on manual tracking . Conclusions The phentermine and dronabinol results demonstrate the validity and sensitivity of the study . Taranabant did not consistently show stimulant/cannabis-like effects or abuse potential in recreational polydrug users , indicating that cannabinoid 1 receptor inverse agonists/antagonists are unlikely to be recreationally abused In determining the effects of regular marihuana use on neurocognition , abilities within specific relevant cognitive domains prior to regular drug use have not been available . The present study examined effects of current and past regular use of marihuana in subjects for whom pre-drug performance had been ascertained in a prospect i ve , longitudinal fashion . A total of 113 young adults , assessed since infancy , were evaluated using neurocognitive tests for which commensurate measures were obtained prior to the initiation of marihuana smoking . Marihuana users , determined by urinalysis and self-report , were categorized as light ( < 5 joints per week ) and heavy ( > or = 5 joints per week ) current users and former users , the latter having used the drug regularly in the past ( > or = 1 joint per week ) but not for at least 3 months . A third of the subjects were using marihuana on a regular basis at the time of assessment with half being heavy users . Among former , regular users , approximately half had been smoking 5 or more joints per week . Overall IQ , memory , processing speed , vocabulary , attention , and abstract reasoning were assessed . After accounting for potentially confounding factors and pre-drug performance in the appropriate cognitive domain , current regular heavy users did significantly worse than non-users in overall IQ , processing speed , immediate , and delayed memory . In contrast , the former marihuana smokers did not show any cognitive impairments . It was concluded that residual marihuana effects are evident beyond the acute intoxication period in current heavy users after taking into account pre-drug performance but similar deficits are no longer apparent 3 months after cessation of regular use , even among former heavy using young adults Marijuana dependence is a substantial public health problem , with existing treatments showing limited efficacy . In laboratory and clinical studies , the cannabinoid receptor 1 agonist oral Δ9tetrahydrocannabinol ( THC ; dronabinol ) has been shown to decrease marijuana withdrawal but not relapse . Dronabinol has poor bioavailability , potentially contributing to its failure to decrease relapse . The synthetic THC analogue , nabilone , has better bioavailability than dronabinol . We therefore aim ed to characterize nabilone 's behavioral and physiological effects across a range of acute doses in current marijuana smokers and compare these with dronabinol 's effects . Participants ( 4 female ; 10 male ) smoking marijuana 6.6 ( st and ard deviation = 0.7 ) days/week completed this outpatient , within‐subjects , double‐blind , r and omized protocol . Over seven sessions , the time‐dependent subjective , cognitive and cardiovascular effects of nabilone ( 2 , 4 , 6 , 8 mg ) , dronabinol ( 10 , 20 mg ) and placebo were assessed . Nabilone ( 4 , 6 , 8 mg ) and dronabinol ( 10 , 20 mg ) increased ratings of feeling a good effect , a strong effect and /or ‘ high ’ relative to placebo ; nabilone had a slower onset of peak subjective effects than dronabinol . Nabilone ( 6 , 8 mg ) modestly lowered psychomotor speed relative to placebo and dronabinol . There were dose‐dependent increases in heart rate after nabilone , and nabilone ( 2 mg ) and dronabinol ( 10 mg ) decreased systolic blood pressure . Thus , nabilone produced sustained , dose‐related increases in positive mood , few cognitive decrements and lawful cardiovascular alterations . It had a longer time to peak effects than dronabinol , and effects were more dose‐related , suggesting improved bioavailability . Nabilone was well tolerated by marijuana smokers , supporting further testing as a potential medication for marijuana dependence |
764 | 29,744,772 | However , across approaches , short-term benefits were seen .
IBS symptoms improved significantly among patients in cognitive and behavioral therapies , mindfulness-based stress reduction , guided affective imagery , and emotional awareness training compared with controls ; there was a similar trend for gut-directed hypnotherapy . | Background Psychological treatments are efficacious for irritable bowel syndrome ( IBS ) in clinical trials ; however , their effectiveness when conducted in gastroenterology practice setting s is unclear .
Aim To perform a systematic review of the types and effects of psychological treatments for IBS conducted in gastroenterology clinics . | BACKGROUND Despite the rapidly growing body of literature on health-related quality of life ( HRQoL ) . placing the results in a context that is meaningful to clinicians and patients is often overlooked . OBJECTIVE This study sought to quantify the impact of irritable bowel syndrome ( IBS ) on HRQoL by comparing the Medical Outcomes Study 36-item Short-Form Health Survey ( SF-36 ) scores of IBS patients with normative US data and with the scores of patients having other chronic gastrointestinal ( GI ) and non-GI disorders . METHODS Two IBS reference groups were identified from the published literature : a largely untreated community sample of health maintenance organization ( HMO ) members ( N = 92 ) and a sample of patients with IBS recruited through clinics and in the community ( N = 140 ) . SF-36 scores for these groups were compared with published US population norms ( N = 2474 ) and with published scores for 3 other IBS sample s ( N = 464 ) ; a sample with other chronic GI disorders ( dyspepsia [ N = 126 ] , gastroesophageal reflux disease [ GERD ] [ N = 516 ] ) ; and sample s with other chronic episodic disorders ( asthma [ N = 375 ] , migraine [ N = 303 ] , panic disorder [ N = 73 ] , rheumatoid arthritis [ N = 693 ] ) . RESULTS The scores of patients in both IBS reference groups were significantly lower on several SF-36 domains than those of the US normative population ( P < 0.003 ) . Scores on several SF-36 scales were also significantly lower in the IBS reference groups compared with the GERD , asthma , and migraine sample s ( P < 0.003 ) . Depending on the IBS sample used , scores did not differ or were higher compared with those in the sample with dyspepsia . Relative to the sample s with panic disorder and rheumatoid arthritis , the IBS groups had significantly higher scores on most SF-36 domains ( P < 0.003 ) . Scores for the HMO reference group were generally higher than those for the clinic/community reference group . CONCLUSIONS Based on the results of this analysis , IBS is associated with impairment of HRQoL relative to US population norms and to population s with GERD , asthma , or migraine . HRQoL appears to be greater in patients with IBS than in those with panic disorder or rheumatoid arthritis , although the relative symptom severity in these sample s was not known Objective . This r and omized trial evaluated the therapeutic effect of emotional awareness training on the severity and frequency of pain in patients with irritable bowel syndrome ( IBS ) . Patients ’ level of alexithymia was also measured . Method . The study involved 100 patients diagnosed with IBS according to the Rome-III criteria . Patients ’ mean age was 34.98 years ( st and ard deviation 10.22 years ) and 60 % of the patients were female . Seventy eligible patients were assigned r and omly to one of two treatment groups . One group received st and ard symptom-oriented medical treatment only ( MT group ) , while the second group , termed the emotional awareness group ( EMT ) , was educated to increase conscious awareness of eight primary emotions in addition to receiving st and ard symptom-oriented medical treatment . This study was conducted over 20 months . All patients received 5 weeks of symptom-oriented medical treatment ; patients in the EMT group also had two emotion awareness training sessions and recorded their emotions in a daily diary . Sixty patients completed the study . Results . Patients with IBS scored significantly higher on all aspects of alexithymia compared with healthy controls . The severity of pain decreased significantly in both groups , with a larger percentage of the patients in the EMT group who completed the study having a significant decrease in pain ( 54 % in the EMT group vs. 36 % in the MT group ) ; this finding was replicated in an intent-to-treat analysis . The same results were observed for frequency of pain in patients who completed the study ( 59 % in the EMT group vs 43.4 % in the MT group ) , but this finding was not replicated in an intent-to-treat analysis . These patterns were not influenced by level of alexithymia , age , or gender . Conclusion . Adding emotional awareness training to medical treatment result ed in a better therapeutic response in abdominal pain in patients with IBS . ( Journal of Psychiatric Practice 2014;20:3–11 Background Internet-based cognitive behavior therapy ( ICBT ) has shown promising effects in the treatment of irritable bowel syndrome ( IBS ) . However , to date no study has used a design where participants have been sample d solely from a clinical population . We aim ed to investigate the acceptability , effectiveness , and cost-effectiveness of ICBT for IBS using a consecutively recruited sample from a gastroenterological clinic . Methods Sixty-one patients were r and omized to 10 weeks of ICBT ( n = 30 ) or a waiting list control ( n = 31 ) . The ICBT was guided by an online therapist and emphasized acceptance of symptoms through exposure and mindfulness training . Severity of IBS symptoms was measured with the Gastrointestinal symptom rating scale - IBS version ( GSRS-IBS ) . Patients in both groups were assessed at pre- and post-treatment while only the ICBT group was assessed 12 months after treatment completion . Health economic data were also gathered at all assessment points and analyzed using bootstrap sampling . Results Fifty of 61 patients ( 82 % ) completed the post-treatment assessment and 20 of 30 patients ( 67 % ) in the ICBT group were assessed at 12-month follow-up . The ICBT group demonstrated significantly ( p < .001 ) larger improvements on the IBS-related outcome scales than the waiting list group . The between group effect size on GSRS-IBS was Cohen 's d = 0.77 ( 95 % CI : 0.19 - 1.34 ) . Similar effects were noted on measures of quality of life and IBS-related fear and avoidance behaviors . Improvements in the ICBT group were maintained at 12-month follow-up . The ICBT condition was found to be more cost-effective than the waiting list , with an 87 % chance of leading to reduced societal costs combined with clinical effectiveness . The cost-effectiveness was sustained over the 12-month period . Conclusions ICBT proved to be a cost-effective treatment when delivered to a sample recruited from a gastroenterological clinic . However , many of the included patients dropped out of the study and the overall treatment effects were smaller than previous studies with referred and self-referred sample s. ICBT may therefore be acceptable and effective for only a subset of clinical patients . Study dropout seemed to be associated with severe symptoms and large impairment . Objective and empirically vali date d criteria to select which patients to offer ICBT should be developed . Trial Registration Clinical Trials.gov : OBJECTIVES : Gut-directed hypnotherapy has been found to be effective in irritable bowel syndrome ( IBS ) . However , r and omized , controlled studies are rare and few have been performed outside highly specialized research centers . The objective of this study was to study the effect of gut-directed hypnotherapy in IBS in different clinical setting s outside the traditional research units . METHODS : The study population included IBS patients refractory to st and ard management . In study 1 , patients were r and omized to receive gut-directed hypnotherapy ( 12 sessions , 1 h/week ) in psychology private practice s or supportive therapy , whereas patients were r and omized to receive gut-directed hypnotherapy in a small county hospital or to serve as waiting list controls in study 2 . Gastrointestinal symptom severity and quality of life were evaluated at baseline , at 3 months follow-up and after 1 year . RESULTS : We r and omized 138 IBS patients refractory to st and ard management , 90 in study 1 and 48 in study 2 . In both the studies , IBS-related symptoms were improved at 3 months in the gut-directed hypnotherapy groups ( P<0.05 ) , but not in the control groups ( ns ) . In study 1 , a significantly greater improvement of IBS-related symptom severity could be detected in the gut-directed hypnotherapy group than in the control group ( P<0.05 ) , and a trend in the same direction was seen in study 2 ( P=0.17 ) . The results seen at 3 months were sustained up to 1 year . CONCLUSIONS : Gut-directed hypnotherapy is an effective treatment alternative for patients with refractory IBS , but the effectiveness is lower when the therapy is given outside the highly specialized research centers Introduction The study aims to investigate two kinds of treatment in patients suffering from irritable bowel syndrome ( IBS ) and consequently compares its efficacy on improving the symptoms and mental health of patients ; one with just medical treatment and another through a combination of psychotherapy and medical treatment . Material and methods Applying general sampling , 50 IBS patients were selected from among those who used to refer to a Gastroenterology Clinic . After physical and mental evaluations based on ROME-II scale and SCL-90-R question naires , the subjects were r and omly superseded into : the control group with medical treatment and , the case group with a combination of medical and psychological treatments . The acquired data were then analyzed through t-test and Mann-Whitney U-test . Results The findings show that the mental health of patients receiving cognitive behavioral therapy along with the medical treatment was higher than those of the control group at post-test level . It was observed that the therapy reduces the disability caused by IBS . Comparatively , while the cognitive therapy and medical treatments cured 80 % of the patients , those receiving cognitive therapy alone showed an extensive reduction of symptoms . Conclusions Considering the role of cognitive behavioral therapy , it is therefore recommend that such patients be managed by a combined team of gastroenterologists and psychologists This study was conducted to evaluate the comparative effect of yogic and conventional treatment in diarrhea-predominant irritable bowel syndrome ( IBS ) in a r and omized control design . The patients were 22 males , aged 20–50 years , with confirmed diagnosis of diarrhea-predominant IBS . The conventional group ( n=12 , 1 dropout ) was given symptomatic treatment with loperamide 2–6 mg/day for 2 months , and the yogic intervention group ( n=9 ) consisted of a set of 12 asanas ( yogic poses , i.e. , Vajrasana , Shashankasana , Ushtrasana , Marjariasana , Padhastasana , Dhanurasana , Trikonasana in two variations , Pawanmuktasana , and Paschimottanasana ) along with Surya Nadi pranayama ( right-nostril breathing ) two times a day for 2 months . All participants were tested at three regular intervals , at the start of study —0 month , 1 month , and 2 months of receiving the intervention— and were investigated for bowel symptoms , autonomic symptoms , autonomic reactivity ( battery of five st and ard tests ) , surface electrogastrography , anxiety profile by Spielberger 's Self Evaluation Question naire , which evaluated trait and state anxiety . Two months of both conventional and yogic intervention showed a significant decrease of bowel symptoms and state anxiety . This was accompanied by an increase in electrophysiologically recorded gastric activity in the conventional intervention group and enhanced parasympathetic reactivity , as measured by heart rate parameters , in yogic intervention group . The study indicates a beneficial effect of yogic intervention over conventional treatment in diarrhea-predominant IBS One hundred two patients with irritable bowel syndrome were studied in a controlled trial of psychological treatment involving psychotherapy , relaxation , and st and ard medical treatment compared with st and ard medical treatment alone . Patients were only selected if their symptoms had not improved with st and ard medical treatment over the previous 6 months . At 3 months , the treatment group showed significantly greater improvement than the controls on both gastroenterologists ' and patients ' ratings of diarrhea and abdominal pain , but constipation changed little . Good prognostic factors included overt psychiatric symptoms and intermittent pain exacerbated by stress , whereas those with constant abdominal pain were helped little by this treatment . This study has demonstrated that psychological treatment is feasible and effective in two thirds of those patients with irritable bowel syndrome who do not respond to st and ard medical treatment Background Irritable bowel syndrome ( IBS ) is a functional disorder of the lower gastrointestinal ( GI ) tract affected by stress , which may benefit from a biopsychosocial treatment approach such as mindfulness-based stress reduction ( MBSR ) . Purpose A treatment as usual ( TAU ) wait-list controlled trial was conducted in Calgary , Canada to investigate the impact of MBSR on IBS symptoms . It was hypothesized that MBSR patients would experience greater reduction in overall IBS symptom severity and self-reported symptoms of stress relative to control patients . Method Ninety patients diagnosed with IBS using the Rome III criteria were r and omized to either an immediate MBSR program ( n = 43 ) or to wait for the next available program ( n = 47 ) . Patients completed IBS symptom severity , stress , mood , quality of life ( QOL ) , and spirituality scales pre- and post-intervention or waiting period and at 6-month follow-up . Intent-to-treat linear mixed model analyses for repeated measures were conducted , followed by completers analyses . Results While both groups exhibited a decrease in IBS symptom severity scores over time , the improvement in the MBSR group was greater than the controls and was clinical ly meaningful , with symptom severity decreasing from constantly to occasionally present . Pre- to post-intervention dropout rates of 44 and 23 % for the MBSR and control groups , respectively , were observed . At 6-month follow-up , the MBSR group maintained a clinical ly meaningful improvement in overall IBS symptoms compared to the wait-list group , who also improved marginally , result ing in no statistically significant differences between groups at follow-up . Improvements in overall mood , QOL , and spirituality were observed for both groups over time . Conclusions The results of this trial provide preliminary evidence for the feasibility and efficacy of a mindfulness intervention for the reduction of IBS symptom severity and symptoms of stress and the maintenance of these improvements at 6 months post-intervention . Attention and self-monitoring and /or anticipation of MBSR participation may account for smaller improvements observed in TAU patients OBJECTIVE : Although the st and ard treatments for the irritable bowel syndrome ( IBS ) are medical , growing evidence indicates the substantial therapeutic value of psychological therapy . However , it has not been investigated whether the combination of multicomponent behavioral therapy plus medical treatment is more effective than medical treatment alone . The aim of this study was to investigate this question in patients consulting a tertiary gastrointestinal ( GI ) referral center . METHODS : Twenty-four IBS out patients were r and omly assigned to the combination of st and ardized multicomponent behavioral therapy plus st and ard medical treatment ( SMBT ) or st and ard medical treatment alone ( SMT ) . SMBT included IBS information and education , progressive muscle relaxation , training in illness-related cognitive coping strategies , problem-solving , and assertiveness training in 10 sessions over 10 wk . SMT included st and ardized symptom-oriented medical treatment and regular visits to a gastroenterologist every second week . Posttreatment outcome measures consisted of quantification of GI , vegetative , and psychological symptoms by means of daily symptom diaries and the assessment of changes in rectovisceral perception thresholds , as well as of question naire measures on psychological distress , overall well-being , illness-related coping abilities , and quality of life . Follow-ups were conducted at 3- and 6-month intervals . RESULTS : Pre- and posttreatment evaluations showed significantly ( p < 0.01 ) greater IBS symptom reduction as measured by daily symptom diaries for the SMBT group than for the SMT group . Rectovisceral perception remained unchanged by either treatment . Overall well-being significantly improved in the SMBT group but remained unchanged in the SMT group . Subjects in the SMBT group , unlike those in the SMT group , felt significantly more in control of their health , and quality of life was significantly improved in the SMBT group but remained unchanged in the SMT group . CONCLUSIONS : The data provide evidence that the combination of medical treatment plus multicomponent behavioral treatment is superior to medical treatment alone in the therapy of IBS BACKGROUND & AIMS Psychotherapy and antidepressants are effective in patients with severe irritable bowel syndrome ( IBS ) , but the cost-effectiveness of either treatment in routine practice has not been established . METHODS Patients with severe IBS were r and omly allocated to receive 8 sessions of individual psychotherapy , 20 mg daily of the specific serotonin reuptake inhibitor ( SSRI ) antidepressant , paroxetine , or routine care by a gastroenterologist and general practitioner . Primary outcome measures of abdominal pain , health-related quality of life , and health care costs were determined after 3 months of treatment and 1 year later . RESULTS A total of 257 subjects ( 81 % response rate ) from 7 hospitals were recruited ; 59 of 85 patients ( 69 % ) r and omized to psychotherapy and 43 of 86 ( 50 % ) of the paroxetine group completed the full course of treatment . Both psychotherapy and paroxetine were superior to treatment as usual in improving the physical aspects of health-related quality of life ( SF-36 physical component score improvement , 5.2 [ SEM , 1.26 ] , 5.8 [ SEM , 1.0 ] , and -0.3 [ SEM , 1.17 ] ; P < 0.001 ) , but there was no difference in the psychological component . During the follow-up year , psychotherapy but not paroxetine was associated with a significant reduction in health care costs compared with treatment as usual ( psychotherapy , $ 976 [ SD , $ 984 ] ; paroxetine , $ 1252 [ SD , $ 1616 ] ; and treatment as usual , $ 1663 [ SD , $ 3177 ] ) . CONCLUSIONS For patients with severe IBS , both psychotherapy and paroxetine improve health-related quality of life at no additional cost Autogenic training ( AT ) is a useful and comprehensive relaxation technique . However , no studies have investigated the effects of AT on irritable bowel syndrome ( IBS ) . In this study we tested the hypothesis that AT improves symptoms of IBS . Twenty-one patients with IBS were r and omly assigned to AT ( n = 11 , 5 male , 6 female ) or control therapy ( n = 10 , 5 male , 5 female ) . AT patients were trained intensively , while the control therapy consisted of discussion s about patients ’ meal habits and life styles . All patients answered a question related to adequate relief ( AR ) of IBS symptoms and four question naires : Self-induced IBS Question naire ( SIBSQ ) , Self-reported Depression Scale ( SDS ) , State-Trait Anxiety Inventory ( STAI ) , and Medical Outcome Short Form 36 Health Survey ( SF-36 ) . The proportion of AR in the last AT session in the AT group ( 9/11 , 81.8 % ) was significantly higher than that in the controls ( 3/10 , 30.0 % , Chi-square test , p = 0.048 ) . Two subscales of the SF-36 , i.e. , social functioning and bodily pain , were significantly improved in the AT group ( p < 0.05 ) as compared to the control group . Role emotional ( p = 0.051 ) and general health ( p = 0.068 ) showed a tendency for improvement in the AT group . AT may be useful in the treatment of IBS by enhancing self-control Irritable bowel syndrome ( IBS ) is a common disorder associated with profoundly impaired quality of life and emotional distress . The management of refractory IBS symptoms remains challenging and non-pharmacological therapeutic approaches have been shown to be effective . We compared brief interventions with biofeedback and hypnotherapy in women referred by their GP with refractory IBS symptoms . Patients were r and omised to one of two treatment groups , biofeedback or hypnotherapy , delivered as three one-hour sessions over 12 weeks . Symptom assessment s were undertaken using vali date d , self-administered question naires . Two of the 128 consecutive IBS patients suitable for the study declined to consider nonpharmacological therapy and 29 patients did not attend beyond the first session . Of the 97 patients r and omised into the study , 21 failed to attend the therapy session ; 15 of 76 patients who attended for therapy dropped out before week 12 post-therapy . The mean ( SD ) change in IBS symptom severity score 12 weeks post-treatment in the biofeedback group was -116.8 ( 99.3 ) and in the hypnotherapy group -58.0 ( 101.1 ) , a statistically significant difference between groups ( difference=-58.8 , 95 % confidence interval [ CI ] for difference [ -111.6 , -6.1 ] , p=0.029 ) . In 61 patients with refractory IBS , biofeedback and hypnotherapy were equally effective at improving IBS symptom severity scores , total non-gastrointestinal symptom scores and anxiety and depression ratings during 24 weeks follow-up . Biofeedback may prove to be the more cost-effective option as it requires less expertise 101 out patients with irritable bowel syndrome were r and omly allocated to two treatment groups . Both groups received the same medical treatment , but patients in one group also received dynamically oriented individual psychotherapy in ten hour-long sessions spread over 3 months . After 3 months there was a significantly greater improvement in somatic symptoms in the psychotherapy group . The difference became more pronounced a year later , with the patients given psychotherapy showing further improvement , and the patients who received medical treatment showing some deterioration . The combination of medical treatment with psychotherapy improves outcome , not only in the short term but also in the long run Thirty-five patients with irritable bowel syndrome were r and omized to receive treatment in a stress management programme or conventional therapy which included the antispasmodic Colpermin . The stress management programme involved a median of six 40-min sessions with a physiotherapist during which patients were helped to underst and the nature of their symptoms , their relationship to stress and were taught relaxation exercises . Two thirds of those in the stress management programme found the programme effective in relieving symptoms and experienced fewer attacks of less severity . This benefit was maintained for at least 12 months . Few of those given conventional management had any benefit . A stress management programme would appear to be of value for patients with irritable bowel syndrome |
765 | 23,818,930 | The underst and ing of TCM Syndrome Differentiation may allow identification of different patterns of disharmony and may provide important guidance to the prescription of CHM . | This paper is a systematic review of evidence -based studies of the effectiveness of Chinese herbal medicine ( CHM ) in the treatment of liver cancer . | PHY906 is a Chinese medicine formula with cl aims for the treatment of severe gastrointestinal distress . PHY906 enhanced the therapeutic index of various chemotherapeutic agents in human hepatocellular carcinoma xenografts . Accordingly , here a phase I/II clinical study was conducted with the combination of capecitabine in patients with advanced , unresectable hepatocellular carcinoma . More than 60 % of patients had either stable disease or better after two treatment cycles . Median overall survival was 9.2 months . Asian patients had a higher median overall survival ( 16.5 months ) than non-Asian patients ( 6.2 months , p=0.03 ) . Patients ' quality of life did not deteriorate significantly during treatment . This finding supported further investigation of PHY906 as an adjuvant therapy of capecitabine in a larger hepatocellular cancer population OBJECTIVE To observe the clinical effect of cinobufacini injection in treating moderate and advanced primary liver cancer ( PLC ) . METHODS One hundred patients with moderate and advanced PLC were r and omly divided into cino-treated group ( 50 patients ) and control group ( 50 patients ) . The quality of life , tumor size , some changes of laboratory tests , and survival time were observed . RESULTS The progressive rate of cino-treated group ( 18 % ) was lower than that of the control group ( 32 % ) . The quality of life of the cino-treated group ( 80 % ) was better than that of the control group ( 72 % ) , but without statistical significance . The survival rate of > 12 months of the cino-treated group ( 30 % ) was higher than that of the control group ( 18 % ) . The patients ' liver function such as serum total bilirubin and ALT decreased obviously in the cino-treated group while increased a lot in the control group . The level of AFP increased after treatment with statistical significance in the control group while there was no statistical significance in the cino-treated group . CONCLUSION Cinobufacini injection can not only inhibit the proliferation of cancer , but also protect liver function , improve quality of life and prolong survival time AIM To investigate anti-tumor activities and apoptosis-regulated mechanisms of bufalin in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice . METHODS BEL-7402 cells of human hepatocellular carcinoma were inoculated to form subcutaneous tumors , and were implanted into the liver to establish orthotopic transplantation tumor models of human hepatocellular carcinoma in nude mice . Seventy-five animals were r and omized divided into five groups ( n = 15 ) . Bufalin was injected intraperitoneally into three groups at doses of 1.5 mg/kg ( BF1 ) , 1 mg/kg ( BF2 ) and 0.5 mg/kg ( BF3 ) for d 15 - 24 , respectively . The NS group was injected an equal volume of saline as above and adriamycin was injected intraperitoneally into the ADM group at a dose of 8.0 mg/kg for d 15 . Ten mice in each group were killed at d 25 and the survival time in each group was calculated . We also observed the morphologic alterations in the myocardium , brain , liver , kidney and tumor tissues by pathology and electron microscopy , measured the apoptotic rate by TUNEL staining method , and detected the expression of apoptosis-regulated genes bcl-2 and bax by immunohistochemical staining and RT-PCR in tumor tissues . RESULTS The tumor volumes in each group of bufalin were reduced significantly ( 35.21 + /- 12.51 vs 170.39 + /- 25.29 ; 49.83 + /- 11.46 vs 170.39 + /- 25.29 ; 83.99 + /- 24.63 vs 170.39 + /- 25.29 , P < 0.01 , respectively ) , and the survival times were prolonged in group BF1 - 2 ( 31.8 + /- 4.2 vs 23.4 + /- 2.1 and 29.4 + /- 3.4 vs 23.4 + /- 2.1 , P < 0.05 , respectively ) , and necrosis was mainly in severe or moderate degree in group BF1 - 2 . No morphological changes were detected in the myocardium , brain , liver and kidney tissues . Apoptotic characteristics could be seen in group BF1 - 2 . The positive rates of bcl-2 and bax protein expression of each group by immunohistochemical staining were 10.0 % , 10.0 % , 20.0 % , 10.0 % and 20.0 % ; 90.0 % , 80.0 % , 80.0 % , 40.0 % and 30.0 % , respectively . Loss of expression of bcl-2 mRNA in each group was to be found and the density of bax mRNA was increased progressively with increase of dose of bufalin by RT-PCR . CONCLUSION Bufalin has significant anti-tumor activities in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice with no marked toxicity and was able to induce apoptosis of transplanted tumor cells . This apoptosis may be mediated mainly via up-regulating the expression of apoptosis-regulated gene bax , which may be involved in its anti-tumor mechanism of bufalin Purpose To study a commonly used Astragalus-based herbal formula previously found effective in non-small cell lung cancer ( NSCLC ) on the pharmacokinetics of docetaxel in patients with NSCLC . Methods Patients with advanced NSCLC who progressed after prior platinum-containing chemotherapy were accrued and received docetaxel at 35 mg/m2 for 3 weeks followed by 1 week of rest . At 4 days prior to the second dosing , Jinfukang was given orally . Pharmacokinetic studies of initial-dose docetaxel ( in the absence of Jinfukang ) and the third dose ( in the presence of Jinfukang ) were compared . Results Of the 24 patients enrolled , 21 started Jinfukang and docetaxel . Jinfukang had no significant impact on the pharmacokinetics of docetaxel . Median time to progression or withdrawal from treatment was 7 weeks . Twelve patients were removed from study for progression of disease ; nine patients withdrew . Conclusions Jinfukang did not alter the pharmacokinetics of docetaxel nor appear to affect survival in this study Huachansu , a Chinese medicine that comes from dried toad venom from the skin gl and s of Bufo gargarizans or B. melanostictus , has been used in the treatment of various cancers in China . The authors conducted a pilot study , using a phase 1 trial design , of huachansu in patients with advanced cancer |
766 | 22,307,577 | The existing evidence supports the use of proton pump inhibitors as a treatment for esophageal reflux disease to improve quality -of-life sleep disturbance – related outcomes . | To perform a systematic literature review that evaluates the impact of proton pump inhibitor treatment of gastroesophageal reflux disease on sleep disturbance – related outcomes . | BACKGROUND Nocturnal gastroesophageal reflux ( nGER ) is common in patients with obstructive sleep apnea ( OSA ) . Small , short-term studies have shown that treatment with nasal continuous positive airway pressure ( CPAP ) decreases esophageal acid exposure . OBJECTIVE To examine the relationship between OSA and nGER , and the effect of CPAP on nGER , in a long-term follow-up study of a large cohort of patients with OSA and nGER . METHODS We prospect ively studied 331 patients diagnosed as having OSA between October 1 , 1993 , and November 30 , 2000 . At baseline , patients grade d their frequency of nGER symptoms on a scale of 1 ( never ) to 5 ( always ) . All patients were prescribed CPAP for their OSA . At follow-up , the frequency of nGER symptoms was obtained by telephone interview . RESULTS Of the 331 patients with OSA , nGER was present in 204 ( 62 % ) before treatment with CPAP . Follow-up was obtained in 181 patients ( 89 % ) . Of these 181 patients , 165 ( 91 % ) were still using CPAP and 16 ( 9 % ) were not , forming the treatment and control groups , respectively . The patients compliant with CPAP had a significant improvement in nGER score , from a mean of 3.38 before CPAP treatment to 1.75 after treatment ( 48 % improvement ; P<.001 ) , while patients not using CPAP ( control subjects ) showed no improvement ( mean , 3.56 to 3.44 ; P = .55 ) . There was a strong correlation between CPAP pressure and improvement in nGER score ( correlation , r = 0.70 ; P<.001 ) , with patients with higher CPAP pressures demonstrating a greater improvement in nGER score . CONCLUSIONS Nocturnal GER is common in patients with OSA . Treatment with nasal CPAP decreases the frequency of nGER symptoms by 48 % . Higher nasal CPAP pressures are associated with greater improvement in nGER OBJECTIVES : Sleep disturbances are common in patients with gastroesophageal reflux disease ( GERD ) . This study examined the effects of esomeprazole on nighttime heartburn , GERD-related sleep disturbances , sleep quality , work productivity , and regular activities . METHODS : This multicenter , r and omized , double-blind , placebo-controlled trial included adults with GERD-associated sleep disturbances and moderate-to-severe nighttime heartburn ( recorded by patient diary during screening ) . Patients received oral esomeprazole 40 mg ( n = 220 ) or 20 mg ( n = 226 ) or placebo ( n = 229 ) once daily for 4 wk . The primary outcome was relief of nighttime heartburn . Secondary outcomes included resolution of sleep disturbances , sleep quality measured by the Pittsburgh Sleep Quality Index ( PSQI ) question naire , and work productivity measured by the Work Productivity and Activity Impairment Question naire . RESULTS : Nighttime heartburn was relieved in 53.1 % ( 111/209 ) , 50.5 % ( 111/220 ) , and 12.7 % ( 28/221 ) of patients who received esomeprazole 40 mg , esomeprazole 20 mg , and placebo , respectively . Differences ( 95 % CI ) versus placebo were 40.5 % ( 32.4 % , 48.5 % ) and 37.8 % ( 29.9 % , 45.7 % ) and were highly significant ( p < 0.0001 ) . GERD-related sleep disturbances resolved in significantly more ( p < 0.0001 ) patients who received esomeprazole 40 ( 73.7 % ) or 20 mg ( 73.2 % ) than in those who received placebo ( 41.2 % ) . Both esomeprazole groups had greater PSQI global score changes from baseline ( p < 0.0001 vs placebo ) and more ( p < 0.0001 vs placebo ) work hours saved per week per patient compared with baseline ( esomeprazole 40 mg , 11.6 h ; esomeprazole 20 mg , 12.3 h ; placebo , 6.2 h ) . CONCLUSIONS : Esomeprazole reduced nighttime heartburn and GERD-related sleep disturbances and improved sleep quality and work productivity Nocturnal gastro-oesophageal reflux has been observed in patients with obstructive sleep apnoea ( OSA ) . Negative intrathoracic pressure during apnoeas and arousal have been suggested as the underlying mechanisms . In order to evaluate this hypothesis , the coincidence and sequence in time of arousal , apnoea and reflux events were analysed . Fifteen patients with OSA or heavy snoring were studied by means of st and ard polysomnograpy with parallel recording of 24-h oesophageal pH. Reflux events during the day were present in all patients , five of whom had symptoms of reflux . In three of these and in five other patients , a total of 69 nocturnal reflux events were found . In 68 events , arousal was found with the reflux event . Only one reflux without arousal was found ( sleep stage 2 ) . Seventeen events occurred during wakefulness after sleep onset . The percentage of time with a pH of < 4 during wakefulness after sleep onset was significantly higher than the percentage of time with a pH of < 4 during total sleep time ( p<0.05 ) . In 37 of the 52 reflux events which occurred during sleep , either an apnoea or a hypopnoea was found prior to the event . The investigation of sequence in time did not prove a causal relation between respiratory events and reflux events . The results indicate that gastro-oesophageal reflux and obstructive sleep apnoea are two separate disorders , which both have a high prevalence in obese patients STUDY OBJECTIVE To estimate the possible association between reported symptoms of gastroesophageal reflux ( GER ) after bedtime , sleep-disordered breathing , respiratory symptoms , and asthma . DESIGN Cross-sectional international population survey . PARTICIPANTS Participants consisted of 2,661 subjects ( age range , 20 to 48 years ) from three countries ( Icel and , Belgium , and Sweden ) , of whom 2,202 were r and omly selected from the general population and 459 were added because of reported asthma . MEASUREMENTS The investigation included a structured interview , spirometry , methacholine challenge , peak flow diary , skin-prick tests , and a question naire on sleep disturbances . RESULTS In the r and om population sample , 101 subjects ( 4.6 % ) reported GER , which was defined as the occurrence of heartburn or belching after going to bed at least once per week . Subjects with nocturnal GER more often were overweight and had symptoms of sleep-disordered breathing than participants not reporting GER . Participants with GER were more likely to report wheezing ( adjusted odds ratio [ OR ] , 2.5 ) , breathlessness at rest ( adjusted OR , 2.8 ) , and nocturnal breathlessness ( adjusted OR , 2.9 ) , and they had increased peak flow variability compared to the subjects without GER . Physician-diagnosed current asthma was reported by 9 % of subjects with GER compared to 4 % of those not reporting GER ( p < 0.05 ) . Subjects with the combination of asthma and GER had a higher prevalence of nocturnal cough , morning phlegm , sleep-related symptoms , and higher peak flow variability than subjects with asthma alone . CONCLUSION The occurrence of GER after bedtime is strongly associated with both asthma and respiratory symptoms , as well as symptoms of obstructive sleep apnea syndrome . The partial narrowing or occlusion of the upper airway during sleep , followed by an increase in intrathoracic pressure , might predispose the patient to nocturnal GER and , consequently , to respiratory symptoms OBJECTIVE : To determine the efficacy of pantoprazole therapy for daytime somnolence , psychomotor vigilance , and quality of life in patients with mild-moderate obstructive sleep disordered breathing ( OSDB ) and gastroesophageal reflux disease ( GERD ) . STUDY DESIGN : R and omized , double-blind , placebo-controlled crossover trial . METHODS : Sixty patients with daytime sleepiness , mildmoderate OSDB and GERD were r and omly assigned a 2-week treatment with pantoprazole 40 mg or placebo followed by a 2-week washout period and crossover respectively to 2-week treatment with placebo or pantoprazole . Outcomes included Epworth Sleepiness Score ( ESS ) , sleep-related quality -of-life ( FOSQ ) , and reaction time . RESULTS : With pantoprazole , patients reported statistically significantly greater improvement of overall reflux symptoms ( P = 0.0003 ) and in ESS ( P = 0.04 ) . A significant improvement was noted in FOSQ for both treatments with a trend toward greater improvement with pantoprazole ( P = 0.058 ) . No improvement in reaction times was observed . CONCLUSION : Patients with coexistent GERD and OSDB noted significant improvement in daytime sleepiness after treatment with pantoprazole over placebo likely related to a reduction in nocturnal reflux-related arousals OBJECTIVES To study the geographical variation in daytime sleepiness , snoring and disrupted breathing during sleep and to identify and compare risk factors using the same method in four European cities . DESIGN A cross-sectional , multicentre epidemiological survey . SETTING Reykjavik in Icel and , Uppsala and Göteborg in Sweden and Antwerp in Belgium . PARTICIPANTS A r and om population sample of 2202 subjects who participated in the European Community Respiratory Health Survey . MAIN OUTCOME MEASURES Sleep disturbances and daytime symptoms . RESULTS At all the centres , 5 % of the men and 2 - 3 % of the women reported snoring every night . Daytime sleepiness ( DS ) was more often reported in Uppsala [ odds ratio ( OR ) and 95 % confidence interval : 1.6 ( 1.2 - 2.1 ) ] than in the other centres , whilst daytime tiredness ( DT ) was most common in Reykjavik [ OR 1.8 ( 1.4 - 2.1 ) ] . Snoring was positively correlated with age , male gender and body-mass index in all areas . Symptoms of gastro-oesophageal reflux were associated with DS : OR 2.6 ( 1.5 4.4 ) and DT : OR 4.5 ( 2.7 - 7.6 ) and disrupted breathing : OR 3.8 ( 1.4 - 10 ) . DS and DT were reported more often by women than by men . CONCLUSION The prevalence of snoring was about the same in all four areas , whilst there was a geographical variation in daytime sleepiness and tiredness . As complaints of DS and DT and disrupted breathing were more common in subjects who reported symptoms of gastro-oesophageal reflux , we suggest that polysomnographic studies comparing sleep patterns in adult patients with and without reflux should be conducted OBJECTIVES : Nocturnal heartburn and related sleep disturbances are common among patients with gastroesophageal reflux disease ( GERD ) . This study evaluated the efficacy of dexlansoprazole MR 30 mg in relieving nocturnal heartburn and GERD-related sleep disturbances , improving work productivity , and decreasing nocturnal symptom severity in patients with symptomatic GERD . METHODS : Patients ( N=305 ) with frequent , moderate-to-very severe nocturnal heartburn and associated sleep disturbances were r and omized 1:1 in a double-blind fashion to receive dexlansoprazole MR or placebo once daily for 4 weeks . The primary end point was the percentage of nights without heartburn . Secondary end points were the percentage of patients with relief of nocturnal heartburn and of GERD-related sleep disturbances over the last 7 days of treatment . At baseline and week 4/final visit , patients completed question naires that assessed sleep quality , work productivity , and the severity and impact of nocturnal GERD symptoms . RESULTS : Dexlansoprazole MR 30 mg ( n=152 ) was superior to placebo ( n=153 ) in median percentage of nights without heartburn ( 73.1 vs. 35.7 % , respectively ; P<0.001 ) . Dexlansoprazole MR was significantly better than placebo in percentage of patients with relief of nocturnal heartburn and GERD-related sleep disturbances ( 47.5 vs. 19.6 % , 69.7 vs. 47.9 % , respectively ; P<0.001 ) , and led to significantly greater improvements in sleep quality and work productivity and decreased nocturnal symptom severity . Adverse events were similar across treatment groups . CONCLUSIONS : In patients with symptomatic GERD , dexlansoprazole MR 30 mg is significantly more efficacious than placebo in providing relief from nocturnal heartburn , in reducing GERD-related sleep disturbances and the consequent impairments in work productivity , and in improving sleep quality / quality of life BACKGROUND During sleep , individuals are uniquely vulnerable to acid reflux . Acid reflux during sleep has been studied by a number of investigators , but non-acid reflux is largely unexplored . METHODS In this study , 15 individuals with significant subjective complaints of heartburn were treated with esomeprazole , 40 mg bid , and with placebo , in r and om order , for 1 week each . After 1 week of treatment , participants underwent combined impedence/pH monitoring and polysomnography . In both drug and placebo conditions , these procedures were done after participants consumed a meal design ed to increase the likelihood of reflux events . RESULTS Total reflux events and acid reflux events were significantly decreased with proton-pump inhibitor ( PPI ) treatment as compared to placebo . Nonacid reflux events were more common with PPI treatment as compared to placebo , but this result was not statistically significant . The ratio of non-acidic to acidic events was significantly greater with PPI treatment , however . Similar results were found for reflux events that occurred only during sleep . Proximal migration of acidic vs non-acidic reflux events was found to be similar . There was no difference in sleep architecture between placebo and drug conditions . CONCLUSION PPI treatment reduced overall reflux events , but non-acidic reflux events were relatively more likely to occur with PPI treatment . The occurrence of these non-acidic reflux events on PPI might conceivably explain why some individuals continue to have symptoms after PPI treatment BACKGROUND Obstructive sleep apnoea has been demonstrated to induce gastrooesophageal reflux through highly negative intrathoracic pressure during the attacks . However , we believe that gastrooesophageal reflux on its part may favour or aggravate the apnoea attacks . AIMS We investigated whether the treatment of gastrooesophageal reflux with omeprazole is able to decrease apnoea attacks . PATIENTS AND METHODS Twenty patients ( mean age 55.4 years , range 49 - 73 years ; 17 males ) with confirmed obstructive sleep apnoea at overnight polysomnography and pathological gastrooesophageal reflux at ambulatory 24-h oesophageal pHmetry were asked to note in a diary the occurrence of apnoea attacks for a basal period of 4 weeks . Subsequently , the patients were r and omly and in a double-blind manner treated with omeprazole 20 mg ( 10 patients , group A ) or placebo ( 10 patients , group B ) by giving 1 cp 30 min before breakfast and 1 cp 30 min before dinner for another 6 weeks with a diary documentation . The results were averaged weekly and over the entire treatment duration and a statistical comparison was made between the groups and within each group before and after treatment . RESULTS The mean weekly frequency of apnoea attacks of group A during the entire period of treatment with omeprazole was significantly decreased with respect to the basal period and was significantly lower than that of group B. The weekly frequency of apnoea attacks in group A started to be significantly lower from the third week than the corresponding values of both group B and the basal period , reaching a decrease of about 73 % in the sixth week . CONCLUSION The occurrence of apnoea attacks progressively decreased during the treatment of gastrooesophageal reflux with omeprazole . This fact suggests that gastrooesophageal reflux may play a role in triggering and /or worsening obstructive sleep apnoea STUDY OBJECTIVES This study was design ed to assess the effect of acid suppression on upper airway structure and function in patients with obstructive sleep apnea syndrome ( OSAS ) and gastroesophageal reflux disease ( GERD ) . METHODS This is a single-site within-subjects design . Twenty five patients with documented mild OSAS and objective ly documented GERD via 24-hour pH measurement were included in the study . Patients were studied before and after 8 weeks of treatment with rabeprazole , 20 mg , twice a day . Subjects underwent laryngoscopy , polysomnography , and 24-hour pH monitoring . Subjective assessment s of sleep obtained included the Pittsburg Sleep Quality Index and the Epworth Sleepiness Scale . RESULTS Posterior commissure edema was significantly reduced ( p < 0.05 ) , and the Reflux Finding Score was improved ( p < 0.07 ) . Objective and subjective sleep parameters were significantly improved , sleep-onset latency was significantly reduced ( 26.2 vs 11.2 , p < 0.05 ) , and sleep-related acid contact time was significantly reduced ( 8.0 % vs 1.7 % p < 0.001 ) . There was no significant change in the apnea-hypopnea index . CONCLUSIONS In patients with mild OSAS and documented GERD , acid suppression improves upper airway abnormalities , as well as objective and subjective measures of sleep quality . Aggressive treatment of GERD in patients with OSAS may be helpful in the overall treatment of this select patient population A number of recent studies have described the presence of significant gastroesophageal reflux ( GER ) in patients with obstructive sleep apnea ( OSA ) . The aims of our studies were to determine the prevalence of this in a controlled population and to investigate the potential for a causal relationship between the two entities by determining whether therapy of OSA altered GER parameters , and vice versa . All patients presenting to our sleep laboratory for screening polysomnography underwent distal esophageal pH monitoring simultaneously with polysomnography . Control subjects were selected if the apnea-hypopnea index ( AHI ) was < 5.0 , and patients were selected if AHI was > 15.0 . Fourteen subjects with OSA undertook a second polysomnographic study including distal esophageal pH monitoring , with nasal continuous positive airway pressure ( nCPAP ) intervention . Twelve subjects with proven OSA took part in a r and omized , placebo-controlled , double-blinded , parallel group study of the effect of antireflux therapy ( nizatidine ) on OSA parameters . In 63 patients and 41 controls , we found that patients with OSA had significantly more GER events than controls as measured by number of reflux events over 8 hours ( 115 vs 23 ; P < 0.001 ) , and percent of time spent at pH < 4.0 ( 21.4 % vs 3.7 % ; P < 0.001 ) . In patients with proven OSA , 53.4 % of GER episodes were temporally related to apneas or hypopneas . Less than half ( 46.8 % ) of all apneas were temporally related to acid reflux , and only 43.8 % of arousals were related to reflux events . In the therapeutic trials , nCPAP reduced GER parameters in both patients with OSA and without OSA , suggesting a nonspecific effect . Antireflux therapy ( nizatidine ) reduced arousals but not apnea-hypopnea index in patients with OSA . Patients with OSA have a higher prevalence of GER than matched control subjects . Nasal CPAP reduces GER parameters nonspecifically , and thus the role of OSA in the pathogenesis of GER remains unclear . GER , however is likely to be important in the pathogenesis of arousals , but there is no evidence that it is involved in the pathogenesis of apneas Background : Several studies have demonstrated that night‐time gastro‐oesophageal reflux affects sleep quality , and thereby impairs daytime functioning Objectives : We test the hypothesis that treatment of gastroesophageal reflux disease ( GERD ) can improve obstructive sleep apnea-hypopnea syndrome ( OSAHS ) . Methods : One hundred forty-six patients with OSAHS underwent a complete history-taking , physical examination , and laboratory testing , including questions related to GERD symptoms . Full-night attended polysomnography , 24-hour wireless pH study at the upper esophagus , snoring level evaluation , Epworth Sleepiness Scale , and quality -of-life surveys were completed for each patient . Patients who tested positive for GERD were treated with esomeprazole magnesium 40 mg once daily for 2 to 12 months . The 24-hour pH study was repeated , and those patients with elimination of GERD were reevaluated by polysomnography , snoring level evaluation , Epworth Sleepiness Scale , quality -of-life surveys , and subjective data collection . Results : Forty-one patients completed single-dose treatment with esomeprazole , but the repeat 24-hour pH study showed that 9 patients had persistent GERD . In the 29 patients who completed phase 2 with normal pH study findings , the snoring level decreased from 9.7 ± 0.5 to 7.9 ± 1.3 ( p < .0001 ) , the Epworth Sleepiness Scale score decreased from 14.2 ± 2.5 to 11.1 ± 2.4 ( p < .0001 ) , the apnea-hypopnea index decreased from 37.9 ± 19.1 to 28.8 ± 11.5 ( p = .006 ) , and the minimum saturation of oxygen increased from 84.1 % ± 7.8 % to 86.9 % ± 5.0 % ( p = .055 ) . Conclusions : Treatment of GERD had a significant impact on the reduction of the apnea-hypopnea index , snoring , and daytime sleepiness . Elimination of GERD should be part of a comprehensive treatment plan for patients with OSAHS The aim of this investigation was to study the geographic variation in sleep complaints and to identify risk factors for sleep disturbances in three European countries : Icel and ( Reykjavik ) , Sweden ( Uppsala and Göteborg ) and Belgium ( Antwerp ) . The study involved a r and om population of 2,202 subjects ( age 20 - 45 years ) who participated in the European Community Respiratory Health Survey . The subjects answered a question naire on sleep disturbances . Participants in Icel and and Sweden also estimated their sleep habits and sleep times during a period of 1 week in a sleep diary . Habitual ( > or = 3/week ) difficulties inducing sleep ( DIS ) were reported by 6 - 9 % and early morning awakenings by 5 - 6 % of the subjects . The estimated number of awakenings and the prevalence of nightmares was significantly lower in Reykjavik . Participants in Reykjavik went to bed at night and woke in the morning approximately 1 hour later than participants at the Swedish centers ( p < 0.001 ) . Symptoms of gastroesophageal reflux ( GER ) were associated with DIS ( odds ratio [ OR ] = 2.7 ) , nightmares ( OR = 4.4 ) , longer sleep latency and frequent nocturnal awakenings . Smoking correlated positively to DIS ( OR = 1.8 ) and estimated sleep latency . We conclude that the prevalence of DIS was fairly similar at these four European centers but that there was a variation in the prevalence of nightmares and nocturnal awakenings . The significant correlation between reported GER and subjective quality of sleep should be followed up in studies using objective measurements OBJECTIVE To determine the effectiveness of Pantoprazole ( Wyeth Pharmaceuticals Inc. , Philadelphia , PA ) therapy for daytime sleepiness in patients with symptoms of acid reflux and obstructive sleep-disordered breathing ( OSDB ) . STUDY DESIGN Prospect i ve interventional cohort study . METHODS Twenty-seven adult subjects ( 67 % men ) with symptoms of acid reflux disease and mild to moderate OSDB were included in a 3-month study of proton pump inhibitor therapy ( Pantoprazole 40 mg once daily ) . Primary outcomes included changes in daytime sleepiness , reflux symptoms , and bed partner assessment of snoring . Secondary outcomes included changes in snoring quantification , apnea , and apnea-hypopnea indices ( AHI ) with SNAP Laboratories ( Glenview , IL ) home sleep study and self-reported global symptom improvement . RESULTS At baseline , patients were typically middle-aged , obese men with mild to moderate sleep apnea ( mean AHI = 15 ) with excessive daytime somnolence ( mean Epworth Sleepiness Score = 13 ) . After 3-month treatment with Pantoprazole , a statistically significant improvement was noted for daytime sleepiness ( P = .002 ) and total reflux symptoms ( P = .0006 ) . Subjects also reported a significant reduction in reflux awakening them from sleep ( P < .0001 ) . Bed-partner assessment of snoring significantly improved ( P = .03 ) ; however , no significant improvements were noted in snoring quantification , apnea , or AHI . When compared with a disease-severity matched historic placebo-control group , this cohort demonstrated a significantly greater reduction in daytime sleepiness ( P = .04 ) . CONCLUSIONS This cohort of subjects had significant improvements in daytime sleepiness and reflux symptoms , including reflux awakening from sleep , with Pantoprazole therapy . Further controlled studies are indicated to confirm these results . Improvement in daytime somnolence likely result ed from a reduction in reflux-related arousals because no improvements occurred in OSDB |
767 | 28,527,230 | RESULTS Our review shows that 1 ) WM abnormality was identified between different subtypes of MCI and healthy controls on diffusion imaging ; 2 ) neither visual ratings of WML nor its volumetry differentiate different subtypes of MCI or its prognosis to dementia ; and 3 ) cognitive correlates of WML were evident in the Amnestic-type MCI in the domains of memory , language , psychomotor speed , attention and executive functions .
CONCLUSION Cognitive reserve and the plasticity of white matter may modulate the impact of WML on the manifestation of the neurodegenerative disease . | BACKGROUND White matter lesions ( WML ) are prevalent in older adults .
The association between WML and cognition in different subtypes of Mild Cognitive Impairment ( MCI ) is inconsistent in the literature .
OBJECTVES We aim to provide a systematic review on the impact of WML in different subtypes of MCI , and discuss the recent findings on white matter plasticity . | Background Mild cognitive impairment ( MCI ) is a condition characterized by memory problems that are more severe than the normal cognitive changes due to aging , but less severe than dementia . Reduced working memory ( WM ) is regarded as one of the core symptoms of an MCI condition . Recent studies have indicated that WM can be improved through computer-based training . The objective of this study is to evaluate if WM training is effective in improving cognitive function in elderly patients with MCI , and if cognitive training induces structural changes in the white and gray matter of the brain , as assessed by structural MRI . Methods / Design sThe proposed study is a blinded , r and omized , controlled trail that will include 90 elderly patients diagnosed with MCI at a hospital-based memory clinic . The participants will be r and omized to either a training program or a placebo version of the program . The intervention is computerized WM training performed for 45 minutes of 25 sessions over 5 weeks . The placebo version is identical in duration but is non-adaptive in the difficulty level of the tasks . Neuropsychological assessment and structural MRI will be performed before and 1 month after training , and at a 5-month folllow-up . Discussion If computer-based training results in positive changes to memory functions in patients with MCI this may represent a new , cost-effective treatment for MCI . Secondly , evaluation of any training-induced structural changes to gray or white matter will improve the current underst and ing of the mechanisms behind effective cognitive interventions in patients with MCI.Trial registration Clinical Trials.gov NCT01991405 . November 18 , 2013 Background and Purpose — MRI is more sensitive than CT for detection of age-related white matter changes ( ARWMC ) . Most rating scales estimate the degree and distribution of ARWMC either on CT or on MRI , and they differ in many aspects . This makes it difficult to compare CT and MRI studies . To be able to study the evolution and possible effect of drug treatment on ARWMC in large patient sample s , it is necessary to have a rating scale constructed for both MRI and CT . We have developed and evaluated a new scale and studied ARWMC in a large number of patients examined with both MRI and CT . Methods — Seventy-seven patients with ARWMC on either CT or MRI were recruited and a complementary examination ( MRI or CT ) performed . The patients came from 4 centers in Europe , and the scans were rated by 4 raters on 1 occasion with the new ARWMC rating scale . The interrater reliability was evaluated by using & kgr ; statistics . The degree and distribution of ARWMC in CT and MRI scans were compared in different brain areas . Results — Interrater reliability was good for MRI ( & kgr;=0.67 ) and moderate for CT ( & kgr;=0.48 ) . MRI was superior in detection of small ARWMC , whereas larger lesions were detected equally well with both CT and MRI . In the parieto-occipital and infratentorial areas , MRI detected significantly more ARWMC than did CT . In the frontal area and basal ganglia , no differences between modalities were found . When a fluid-attenuated inversion recovery sequence was used , MRI detected significantly more lesions than CT in frontal and parieto-occipital areas . No differences were found in basal ganglia and infratentorial areas . Conclusions — We present a new ARWMC scale applicable to both CT and MRI that has almost equal sensitivity , except for certain regions . The interrater reliability was slightly better for MRI , as was the detectability of small lesions Background Older adults free of dementia but with subjective memory complaints ( SMC ) or mild cognitive impairment ( MCI ) are considered at increased risk of cognitive decline . Vascular risk factors ( VRF ) , including hypertension , heart disease , smoking , hypercholesterolemia and lack of physical activity ( PA ) have been identified as modifiable risk factors contributing to cognitive decline , and white matter hyperintensities ( WMH ) are associated with VRF , SMC and cognitive impairment . Findings from a growing number of clinical trials with older adults are providing strong evidence for the benefits of physical activity for maintaining cognitive function , but few studies are investigating these benefits in high-risk population s. The aim of AIBL Active is to determine whether a 24-month physical activity program can delay the progression of white matter changes on magnetic resonance imaging ( MRI ) . Methods / design This single-blind r and omized controlled trial ( RCT ) is offered to 156 participants , aged 60 and older , in the Melbourne arm of the Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging ( AIBL ) . Participants must have SMC with or without MCI and at least one VRF . The PA intervention is a modification of the intervention previously trialed in older adults with SMC and MCI ( Fitness for the Ageing Brain Study ) . It comprises 24 months of moderate , home-based PA ( 150 minutes per week ) and a behavioral intervention package . The primary outcome measure will be change in WMH after 24 months on MRI . Cognition , quality of life , functional fitness , level of physical activity , plasma biomarkers for cerebrovascular disease and amyloid positron emission tomography ( PET ) imaging comprise secondary measures . Discussion Currently , there is no effective pharmacological treatment available to delay cognitive decline and dementia in older adults at risk . Should our findings show that physical activity can slow down the progression of WMH , this RCT would provide an important proof of concept . Since imbedded in AIBL this RCT will also be able to investigate the interaction between vascular and Alzheimer 's disease pathologies . Trial Registration Australia New Zeal and Clinical Trials Registry A growing body of research indicates benefits of cognitive training in older adults , but the neuronal mechanisms underlying the effect of cognitive intervention remains largely unexplored . Neuroimaging methods are sensitive to subtle changes in brain structure and show potential for enhancing our underst and ing of both aging- and training-related neuronal plasticity . Specifically , studies using diffusion tensor imaging ( DTI ) suggest substantial changes in white matter ( WM ) in aging , but it is not known whether cognitive training might modulate these structural alterations . We used tract-based spatial statistics ( TBSS ) optimized for longitudinal analysis to delineate the effects of 8 weeks intensive memory training on WM microstructure . 41 participants ( mean age 61 years ) matched for age , sex and education were r and omly assigned to an intervention or control group . All participants underwent MRI-scanning and neuropsychological assessment s at the beginning and end of the study . Longitudinal analysis across groups revealed significant increase in frontal mean diffusivity ( MD ) , indicating that DTI is sensitive to WM structural alterations over a 10-week interval . Further , group analysis demonstrated positive effects of training on the short-term changes . Participants in the training group showed a relative increase in fractional anisotropy ( FA ) compared with controls . Further , a significant relationship between memory improvement and change in FA was found , suggesting a possible functional significance of the reported changes . The training effect on FA seemed to be driven by a relative decrease in radial diffusivity , which might indicate a role for myelin-related processes in WM plasticity Abstract Non-demented community-dwelling older adults aged 70–90 years ( n = 1,037 ) r and omly recruited from the electoral roll completed neuropsychological and medical assessment s over six years . The overall prevalence of mild cognitive impairment ( MCI ) at baseline was 36.7 % . Risk factors for MCI include APOE ϵ4 allele carrier status , high homocysteine , heart disease , poor odour identification , low visual acuity and low mental activity , but notable age and sex differences were observed . Neuropsychiatric symptoms were rare ; depression was the most common and was associated with cognitive impairment in at least one domain as well as subsequent dementia 2 years later . Poorer cognitively dem and ing functional abilities were associated with cognitive impairment . Biomarkers for cognitive impairment and decline were identified . Inflammatory markers and plasma apolipoprotein levels were associated with poorer performance in the attention/processing speed domain . Measures of white matter lesions , white matter integrity , sulcal morphology and tractography were identified as novel biomarkers of early cognitive decline . Stronger deactivation in the posteromedial cortex with increasing memory load on functional MRI predicted future decline . Compared to previous reports , our prevalence rates of MCI were higher but rates of progression to dementia and reversion to normal were similar , as were risk factors for progression to dementia |
768 | 18,333,556 | Based on the limited available evidence , this article suggests benefits in terms of patient outcomes and reduction in the length of hospitalization after midnight removal of the IUCs . | OBJECTIVE The objective of this systematic review was to determine the effect of the timing of removal of indwelling urethral catheters ( IUCs ) on the duration to and volume of first void , length of hospitalization , number of patients developing urinary retention and requiring recatheterization , patient satisfaction , and the percentage of IUCs removed according to the scheduled time for removal . | In the fields of both nursing and medicine there is a dearth of published literature on the optimum time to remove indwelling urinary catheters ( IDCs ) following urological surgery . Tradition seems to be in favour of removing IDCs at 0600 hours despite a lack of evidence to support this practice . This study was undertaken to determine whether midnight removal of IDCs result ed in patients ' resuming normal voiding patterns . A prospect i ve clinical trial was conducted to determine the impact midnight removal of urinary catheters would have on the patients ' voiding pattern , and subsequent discharge from hospital . One hundred and sixty patients were entered into the study . The patients were allocated at r and om to have their urinary catheter removed either at midnight or at 0600 hours . Patients who had their catheters removed at midnight passed a greater volume of urine with both their first ( 268 ml compared with 177 ml ; P<0.0001 ) and second voids ( 322 ml compared with 195 ml ; P<0.0001 ) than their counterparts in the 0600 group . This permitted earlier discharge from hospital . The results reported in this study support the findings of earlier research that midnight removal of IDC leads to an earlier resumption of normal voiding patterns , permits earlier discharge from hospital and appears to reduce patients ' anxiety . The recommendation from this study is that there should be a change in hospital policy so that the majority of IDCs are removed at midnight Patients who had undergone bladder neck surgery were r and omized to having their urethral catheters removed either early in the morning or late at night . There was no difference in the incidence of urinary retention between these two groups of patients . However , patients who presented with acute urinary retention had a higher incidence of postoperative urinary retention . This study suggests that a urethral catheter may be safely removed in the evening without increasing the risk of urinary retention . There also seems to be no greater chance of the patient having to be recatheterized at an unsocial hour PURPOSE This article describes a study that compares the outcomes of midnight versus early morning urethral catheter removal after transurethral resection of the prostate . SUBJECTS AND SETTING / METHODS : The research setting was a large , metropolitan hospital in Sydney , Australia . Forty-eight patients who had undergone transurethral resection of the prostate were r and omly assigned to either group A , catheter removal at 2400 hours ( n = 20 ) , or group B , catheter removal at 0600 hours ( n = 28 ) . MAIN OUTCOME MEASURES Data collected included time to first void , volume of first void , time between catheter removal and discharge from hospital , weight of prostatic resection , and tissue pathology . RESULTS There was no significant difference between the 2 groups with respect to pathology , weight of prostatic resection , mean volume of first void , or time to first void after catheter removal . There was a significant difference in the time between catheter removal and discharge from hospital . Eighty-five percent of those having catheters removed at 2400 hours were discharged on the same day as catheter removal , as compared with 65 % of those who underwent catheter removal at 0600 hours ( chi 2 = 12.684 ; P < 0.005 ) . CONCLUSION After transurethral resection of the prostate , removal of the urethral catheter at 2400 hours reduced the length of hospital stay , but did not significantly affect the time to first void or the volume of the first void The interval before removal of the catheter used in prostatic transurethral surgery depends to a great extent on the surgeon , with a frequently empirical orientation . We conducted a prospect i ve , r and omized and controlled study of 213 patients who underwent transurethral surgery for benign prostatic hyperplasia . The catheter was removed systematic ally 24 hours after transurethral incision and 48 hours after transurethral resection of the prostate ( group 1 - 52 and 54 patients , respectively ) or the catheterization interval was determined by each surgeon in accordance with the usual criteria ( group 2 - 52 and 55 patients , respectively ) . No statistically significant differences were noted between these 2 groups in regard to complications . We conclude that systematic removal of the catheter at the aforementioned periods is cost-effective , safe and comfortable for the patient This study shows that removal of urinary catheters at midnight has several advantages over removal at 6 AM . The midnight group had a significantly greater initial voided volume and a longer time to first void than the equivalent 6 AM group . Advantages to midnight catheter removal also exist for nursing staff . Midnight tends to be less busy on the nursing unit compared with 6 AM , thus making it a preferable time for performance of routine tasks . Catheter removal at midnight also allows for convenient observation of patient voiding and assessment earlier in the day . This means that any necessary intervention can take place during working hours when more staff are on duty . There is also the potential for earlier discharge , with economic benefits related to shorter bed stay and more efficient discharge planning . We believe midnight catheter removal offers considerable benefits over the traditional 6 AM time on both general and urology units OBJECTIVE To compare three methods for a trial of micturition ( TOM ) ( the midnight removal of the catheter , dawn removal , and a new infusion method ) in a r and omized prospect i ve study . PATIENTS AND METHODS A total of 118 consecutive patients who had undergone transurethral resection of the prostate ( TURP ) or bladder neck incision ( BNI ) underwent TOM by one of the three methods . In the infusion method , the bladder was filled at a fast-drip rate via the catheter from a bag of normal saline connected by an intravenous supply set . The catheter was then removed , the patient voided and the volume was measured . From the volume of saline remaining , it was possible to calculate the residual volume in the patient . RESULTS The infusion TOM took a mean 13 h less than the other two methods , which were statistically indistinguishable . CONCLUSION The infusion TOM is safe and simple , is quick to carry out and can be performed at any time . It establishes the completeness of bladder emptying , which helps in the assessment of voiding A r and omised controlled trial was undertaken to determine the effects of midnight removal of urinary catheters on patients ' voiding patterns and subsequent discharge from hospital . Patients whose urinary catheters were removed at midnight showed a greater volume of initial void than those whose catheters were removed at the usual time of 0600 . Removal of urinary catheters routinely at midnight permits earlier assessment of patients ' voiding , which may allow for earlier discharge from hospital |
769 | 28,703,869 | Participants tended to be a selected elderly group of stroke survivors with moderate disability .
We saw no clear differences in participants ' activities of daily living scores , patients subjective health status or mood , or the subjective health status , mood or satisfaction with services of carers .
Appropriately re source d ESD services with co-ordinated multidisciplinary team input provided for a selected group of stroke patients can reduce long-term dependency and admission to institutional care as well as reducing the length of hospital stay .
Results are inconclusive for services without co-ordinated multidisciplinary team input .
We observed no adverse impact on the mood or subjective health status of patients or carers , nor on readmission to hospital | BACKGROUND People with stroke conventionally receive a substantial part of their rehabilitation in hospital .
Services have now been developed that offer people in hospital an early discharge with rehabilitation at home ( early supported discharge : ESD ) .
OBJECTIVES To establish if , in comparison with conventional care , services that offer people in hospital with stroke a policy of early discharge with rehabilitation provided in the community ( ESD ) can : 1 ) accelerate return home , 2 ) provide equivalent or better patient and carer outcomes , 3 ) be acceptable satisfactory to patients and carers , and 4 ) have justifiable re source implication s use . | BACKGROUND AND PURPOSE The goal of the present study was to examine the re source and economic implication s of an early hospital discharge and home-based rehabilitation scheme for patients with acute stroke . METHODS A cost minimization analysis in conjunction with a r and omized controlled trial was carried out at 2 affiliated teaching hospitals in the southern metropolitan region of Adelaide , South Australia , between 1997 and 1998 . Eighty-six hospitalized patients with acute stroke who required rehabilitation were r and omized to receive both early hospital discharge and home-based rehabilitation , or conventional in-hospital rehabilitation and community care . Direct and indirect costs related to stroke rehabilitation were calculated , including hospital bed days , home-based intervention program , community services , and personal expenses during the 6 months after r and omization . RESULTS The mean cost per patient was lower for patients r and omized to the early hospital discharge and home-based rehabilitation ( $ 8040 ) compared with those who received conventional care ( $ 10 054 ) . This cost saving was not statistically significant ( P=0.14 ) . However , sensitivity analyses indicated that the cost of home-based rehabilitation was consistently lower than that of conventional care except when hospital costs were assumed to be 50 % less than those used in the main analysis . Multiple regression analysis demonstrated that the cost of the home-based program was significantly related to a patient 's level of disability after adjustment for age , comorbidity , and the presence or absence of a caregiver . CONCLUSIONS The early hospital discharge and home-based rehabilitation scheme was less costly than conventional hospital care for patients with stroke . Limitation of the provision of such services to patients with mild disability is likely to be most cost effective Abstract Objectives : To examine the cost of providing hospital at home in place of some forms of inpatient hospital care . Design : Cost minimisation study within a r and omised controlled trial . Setting : District general hospital and catchment area of neighbouring community trust . Subjects : Patients recovering from hip replacement ( n=86 ) , knee replacement ( n=86 ) , and hysterectomy ( n=238 ) ; elderly medical patients ( n=96 ) ; and patients with chronic obstructive airways disease ( n=32 ) . Interventions : Hospital at home or inpatient hospital care . Main outcome measures : Cost of hospital at home scheme to health service , to general practitioners , and to patients and their families compared with hospital care . Results : No difference was detected in total healthcare costs between hospital at home and hospital care for patients recovering from a hip or knee replacement , or elderly medical patients . Hospital at home significantly increased healthcare costs for patients recovering from a hysterectomy ( ratio of geometrical means 1.15 , 95 % confidence interval 1.04 to 1.29 , P=0.009 ) and for those with chronic obstructive airways disease ( Mann-Whitney U test , P=0.01 ) . Hospital at home significantly increased general practitioners ' costs for elderly medical patients ( Mann-Whitney U test , P<0.01 ) and for those with chronic obstructive airways disease ( P=0.02 ) . Patient and carer expenditure made up a small proportion of total costs . Conclusion : Hospital at home care did not reduce total healthcare costs for the conditions studied in this trial , and costs were significantly increased for patients recovering from a hysterectomy and those with chronic obstructive airways disease . There was some evidence that costs were shifted to primary care for elderly medical patients and those with chronic obstructive airways disease . Key messages Hospital at home schemes are a popular alternative to st and ard hospital care , but there is uncertainty about their cost effectiveness In our r and omised controlled trial we compared the cost of hospital at home care with that of inpatient hospital care for patients recovering from hip replacement , knee replacement , and hysterectomy ; elderly medical patients ; and those with chronic obstructive airways disease There were no major differences in health service costs between the two arms of the trial for patients recovering from hip or knee replacement and elderly medical patients Hospital at home care increased healthcare costs for patients recovering from hysterectomy and for those with chronic obstructive airways disease Hospital at home care result ed in some costs shifting to general practitioners for elderly medical patients and those with chronic obstructive airways Background and Purpose — Early supported discharge ( ESD ) for stroke has been shown to yield outcomes similar to or better than those of conventional care , but there is less information on the impact on costs and on the caregiver . The purpose of this study is to estimate the costs associated with an ESD program compared with those of usual care . Methods — We conducted a r and omized controlled trial of stroke patients who required rehabilitation services and who had a caregiver at home . Results — Acute-care costs incurred before r and omization when patients were medically ready for discharge averaged $ 3251 per person . The costs for the balance of the acute-care stay , from r and omization to discharge , were $ 1383 for the home group and $ 2220 for the usual care group . The average cost of providing the 4-week home intervention service was $ 943 per person . The total cost generated by persons assigned to the home group averaged $ 7784 per person , significantly lower than the $ 11 065 per person for those assigned to usual care . A large proportion of the cost differential between the 2 groups arose from readmissions , for which the usual care group generated costs more than quadruple those of the home intervention group . Conclusions — Providing care at home was no more ( or less ) expensive for those with greater functional limitation than for those with less . Caregivers in the ESD group scored consistently lower on the Burden Index than caregivers with usual care , even caregivers of persons with major functional limitations . For persons recovering from stroke and their families , ESD provides a cost-effective alternative to usual care Background and Purpose — This proof-of-concept trial investigated the effects of an 8-week program of caregiver-mediated exercises commenced in hospital combined with tele-rehabilitation services on patient self-reported mobility and caregiver burden . Methods — Sixty-three hospitalized stroke patients ( mean age 68.7 , 64 % female ) were r and omly allocated to an 8-week caregiver-mediated exercises program with e-health support or usual care . Primary outcome was the Stroke Impact Scale mobility domain . Secondary outcomes included length of stay , other Stroke Impact Scale domains , readmissions , motor impairment , strength , walking ability , balance , mobility , ( extended ) activities of daily living , psychosocial functioning , self-efficacy , quality of life , and fatigue . Additionally , caregiver ’s self-reported fatigue , symptoms of anxiety , self-efficacy , and strain were assessed . Assessment s were completed at baseline and at 8 and 12 weeks . Results — Intention-to-treat analysis showed no between-group difference in Stroke Impact Scale mobility ( P=0.6 ) ; however , carers reported less fatigue ( 4.6 , confidence interval [ CI ] 95 % 0.3–8.8 ; P=0.04 ) and higher self-efficacy ( −3.3 , CI 95 % −5.7 to −0.9 ; P=0.01 ) at week 12 . Per- protocol analysis , examining those who were discharged home with tele-rehabilitation demonstrated a trend toward improved mobility ( −9.8 , CI 95 % −20.1 to 0.4 ; P=0.06 ) , significantly improved extended activities of daily living scores at week 8 ( −3.6 , CI 95 % −6.3 to −0.8 ; P=0.01 ) and week 12 ( 3.0 , CI 95 % −5.8 to −0.3 ; P=0.03 ) , a 9-day shorter length of stay ( P=0.046 ) , and fewer readmissions over 12 months ( P<0.05 ) . Conclusions — Caregiver-mediated exercises supported by tele-rehabilitation show promise to augment intensity of practice , result ing in improved patient-extended activities of daily living , reduced length of stay with fewer readmissions post stroke , and reduced levels of caregiver fatigue with increased feelings of self-efficacy . The current findings justify a larger definite phase III r and omized controlled trial . Clinical Trial Registration — URL : http://www.anzctr.org.au . Unique identifier : ACTRN12613000779774 Background Development of longer term stroke rehabilitation services is limited by lack of evidence of effectiveness for specific interventions and service models . We describe the protocol for a multicentre r and omised controlled trial which is evaluating an extended stroke rehabilitation service . The extended service commences when routine ‘ organised stroke care ’ ( stroke unit and early supported discharge ( ESD ) ) ends . Methods / design This study is a multicentre r and omised controlled trial with health economic and process evaluations . It is set within NHS stroke services which provide ESD . Participants are adults who have experienced a new stroke ( and carer if appropriate ) , discharged from hospital under the care of an ESD team . The intervention group receives an extended stroke rehabilitation service provided for 18 months following completion of ESD . The extended rehabilitation service involves regular contact with a senior ESD team member who leads and coordinates further rehabilitation . Contact is usually by telephone . The control group receives usual stroke care post-ESD . Usual care may involve referral of patients to a range of rehabilitation services upon completion of ESD in accordance with local clinical practice . R and omisation is via a central independent web-based service . The primary outcome is extended activities of daily living ( Nottingham Extended Activities of Daily Living Scale ) at 24 months post-r and omisation . Secondary outcomes ( at 12 and 24 months post-r and omisation ) are health status , quality of life , mood and experience of services for patients , and quality of life , experience of services and carer stress for carers . Re source use and adverse events are also collected . Outcomes are undertaken by a blinded assessor . Implementation and delivery of the extended stroke rehabilitation service will also be described . Semi-structured interviews will be conducted with a sub sample of participants and staff to gain insight into perceptions and experiences of rehabilitation services delivered or received . Allowing for 25 % attrition , 510 participants are needed to provide 90 % power to detect a difference in mean Nottingham Extended Activities of Daily Living Scale score of 6 with a 5 % significance level . Discussion The provision of longer term support for stroke survivors is currently limited . The results from this trial will inform future stroke service planning and configuration . Trial registration This trial was registered with IS RCT N ( identifier : IS RCT N45203373 ) on 9 August 2012 Background and Purpose — Early supported discharge from a stroke unit reduces the length of hospital stay . Evidence of a benefit for the patients is still unknown . The aim of this trial was to evaluate the long-term effects of an extended stroke unit service ( ESUS ) , characterized by early supported discharge . The short-term effects were published previously . Methods — We performed a r and omized controlled trial in which 320 acute stroke patients were allocated to either ordinary stroke unit service ( OSUS ) ( 160 patients ) or stroke unit care with early supported discharge ( 160 patients ) . The ESUS consists of a mobile team that coordinates early supported discharge and further rehabilitation . Primary outcome was the proportion of patients who were independent as assessed by modified Rankin Scale ( RS ) ( RS ≤2=global independence ) . Secondary outcomes measured at 52 weeks were performance on the Barthel Index ( BI ) ( BI ≥95=independent in activities of daily living ) , differences in final residence , and analyses to identify patients who benefited most from an early supported discharge service . All assessment s were blinded . Results — We found that 56.3 % of the patients in the ESUS versus 45.0 % in the OSUS were independent ( RS ≤2 ) ( P = 0.045 ) . The number needed to treat to achieve 1 independent patient in ESUS versus OSUS was 9 . The odds ratio for independence was 1.56 ( 95 % CI , 1.01 to 2.44 ) . There were no significant differences in BI score and final residence . Patients with moderate to severe stroke benefited most from the ESUS . Conclusions — Stroke service based on treatment in a stroke unit combined with early supported discharge appears to improve the long-term clinical outcome compared with ordinary stroke unit care . Patients with moderate to severe stroke benefit most Background and Purpose — Early supported discharge ( ESD ) seems to be a promising alternative to conventional follow-up care after acute stroke . We have previously shown that stroke unit care combined with ESD has beneficial effects on functional outcome and the use of re sources for up to 1 year . The aim of this trial was to evaluate outcome after 5 years . Methods — We performed a r and omized controlled trial with 320 acute stroke patients allocated to ordinary stroke unit care ( 160 patients ) or stroke unit care with ESD ( 160 patients ) . The ESD service consisted of a mobile team that co-coordinated hospital discharge and further rehabilitation during 1 month of follow-up in cooperation with the primary health care . Mortality , residence , and functional outcome including modified Rankin scale were registered after 5 years . All assessment s were blinded . Results — There was no difference between the groups with modified Rankin scale score ⩽2 ( P=0.213 ) , but there was a trend toward greater improvement in modified Rankin scale score in the ESD group from onset of stroke ( 38 % versus 30 % ; P=0.106 ) . More patients were dead or institutionalized in the ordinary stroke unit care group ( P=0.032 ) ; 158 patients were alive , 84 were in ESD , and 74 were in ordinary stroke unit care . Of the 158 patients alive , a greater proportion were living at home in ESD ( 86%/70 % ; P=0.019 ) . Conclusions — Stroke unit care combined with ESD seems to reduce death and institutional care and to improve patients ' chances of living at home 5 years after stroke compared to traditional stroke care . There is a trend toward improved functional outcome in the ESD group Purpose : To evaluate the feasibility and effectiveness of early supported discharge ( ESD ) following acute stroke . Method : An ESD scheme was compared to conventional rehabilitation in a r and omized controlled trial . All patients admitted with acute stroke were considered for inclusion . Eighty-eight ( 20.2 % ) were found to be eligible and 82 were r and omized either to early supported discharge ( n=42 ) or conventional rehabilitation ( n=40 ) . The primary outcome measure was the Nottingham Extended Activities of Daily Living Scale . The General Health Question naire , the Montgomery Aasberg Depression Rating Scale , mortality , placement and patient and carer satisfaction served as secondary outcome measures . Results : Median length of stay was reduced from 31 days in the conventional hospital rehabilitation group to 22 days in the early supported discharge group ( p=0.09 ) . No differences were found regarding primary outcome . The General Health Question naire score showed a significant difference in favour of the early supported discharge group at three months ( 19.5/24 , p = 0.02 ) , but not at six . At six months , the proportion of patients being dead or in institution showed a trend of being higher in the conventional rehabilitation group ( OR 3.8 , 95 % CI 0.8 - 23 ) . Conclusions : Early supported discharge after stroke is feasible and it is possible that it has benefits compared with conventional rehabilitation Background and Purpose — Readmission rate within 6 months after a stroke is 40 % to 50 % . The purpose of the project was to evaluate whether an interdisciplinary stroke team could reduce length of hospital stay , readmission rate , increase patient satisfaction and reduce dependency of help . Methods — One hundred and ninety-eight patients with acute stroke were r and omized into 103 patients whose discharge was supported by an interdisciplinary stroke team and 95 control patients who received st and ard aftercare . Baseline characteristics were comparable in the 2 groups . The patients were evaluated after 6 and 12 months regarding functional status and need for help . Results — Length of hospital admission was insignificantly shorter in the intervention compared with the control group ( 35.2 versus 39.8 days ) . There was no significant difference in readmission , GP-visits , and primary health care services . Furthermore , there was no significant difference in functional scores or patient satisfaction . Conclusions — In this setting we could not show benefit of an interdisciplinary stroke team supporting patients at discharge perhaps because st and ard aftercare was very efficient already Background and Purpose — The optimal organization of rehabilitation services after discharge from a stroke unit has not been determined . This study sought to evaluate the effect of early supported discharge and continued rehabilitation at home ( ESD ) , in terms of patient outcome 5 years after stroke and changes in selected data over time . Methods — Eighty-three patients from Southwest Stockholm , mildly or moderately impaired 5 to 7 days after acute stroke , were enrolled in a r and omized controlled trial . The core components of the ESD service were initial treatment in a stroke unit and the involvement of an outreach team to deliver and coordinate home-based rehabilitation in partnership with the patient . At the 5-year follow-up , measures used to assess patient outcome included survival , motor capacity , dysphasia , activities of daily living ( ADL ) , social activities , subjective dysfunction , and self-reported falls . Results — Fifty-four patients ( 30 in the intervention group and 24 in the control group ) were evaluated 5 years after stroke , at which time a significantly larger proportion of patients in the intervention group were independent in extended ADL and active in household activities . Conclusions — This ESD service has a beneficial effect on extended ADL 5 years after stroke for mildly to moderately impaired patients Background : The purpose of this study was to clarify the effects of voluntary training with family participation in addition to conventional rehabilitation for stroke patients . Methods / Design : The subjects were 49 first-time stroke patients with severe hemiplegia . They were divided into two groups : a family participation group , in which voluntary training was performed with family members ( 21 patients ) , and a nonfamily participation group , in which voluntary training was performed with a physical therapist ( 28 patients ) . The groups were compared by background , cognitive and physical function , postadmission course , and outcome . Results : There were shortened lengths of stay and higher rates of home discharge in family participation group , but no differences in functional recovery . Conclusions : Voluntary training with family participation was effective in shortening the length of hospital stay and in improving the rate of home discharge in a convalescent rehabilitation ward Introduction We are undertaking a r and omised controlled trial ( fAmily led rehabiliTaTion aftEr stroke in INDia , ATTEND ) evaluating training a family carer to enable maximal rehabilitation of patients with stroke-related disability ; as a potentially affordable , culturally acceptable and effective intervention for use in India . A process evaluation is needed to underst and how and why this complex intervention may be effective , and to capture important barriers and facilitators to its implementation . We describe the protocol for our process evaluation to encourage the development of in-process evaluation methodology and transparency in reporting . Methods and analysis The realist and RE- AIM ( Reach , Effectiveness , Adoption , Implementation and Maintenance ) frameworks informed the design . Mixed methods include semistructured interviews with health providers , patients and their carers , analysis of quantitative process data describing fidelity and dose of intervention , observations of trial set up and implementation , and the analysis of the cost data from the patients and their families perspective and programme budgets . These qualitative and quantitative data will be analysed iteratively prior to knowing the quantitative outcomes of the trial , and then triangulated with the results from the primary outcome evaluation . Ethics and dissemination The process evaluation has received ethical approval for all sites in India . In low-income and middle-income countries , the available human capital can form an approach to reducing the evidence practice gap , compared with the high cost alternatives available in established market economies . This process evaluation will provide insights into how such a programme can be implemented in practice and brought to scale . Through local stakeholder engagement and dissemination of findings globally we hope to build on patient-centred , cost-effective and sustainable models of stroke rehabilitation . Trial registration number CTRI/2013/04/003557 BACKGROUND AND PURPOSE This study describes the methodology , patient outcome , and use of hospital and rehabilitation services at 3 months of a population -based r and omized controlled trial . The purpose was to evaluate rehabilitation at home after early supported discharge from the Department of Neurology , Huddinge Hospital , for moderately disabled stroke patients in southwest Stockholm . METHODS The patients were eligible if they were continent , independent in feeding , had mental function within normal limits , and had impaired motor function and /or aphasia 1 week after stroke . Patients were r and omized either to early supported discharge with continuity of rehabilitation at home for 3 to 4 months or to routine rehabilitation service in a hospital , day care , and /or outpatient care . The home rehabilitation team consisted of two physical therapists , two occupational therapists , and one speech therapist ; one of the therapists was assigned as case manager for the patient . The rehabilitation program at home emphasized a task- and context -oriented approach . The activities were chosen on the basis of the patient 's personal interests . Spouses were offered education and individual counseling . A total of 81 patients were followed up for a minimum of 3 months . Patient outcome was assessed by the Frenchay Social Activity Index , Extended Katz Index , Barthel Index , Lindmark Motor Capacity Assessment , Nine-Hole Peg Test , walking speed over 10 m , reported falls , and subjective dysfunction according to the Sickness Impact Profile . Patient use of hospital and home rehabilitation service and patient satisfaction with care were studied . RESULTS Overall there were no statistical significant differences in outcome . Multivariate logistic regression analysis suggested a systematic positive effect for the home rehabilitation group in social activity , activities of daily living , motor capacity , manual dexterity , and walking . A considerable difference in re source use during such a 3-month period was seen . A 52 % reduction in hospitalization was observed : from 29 days in the routine rehabilitation group to 14 days in the home rehabilitation group . Patient satisfaction was in favor of the latter group . CONCLUSIONS Early supported discharge with continuity of home rehabilitation services for the majority of moderately disabled stroke patients during the first 3-month period after acute stroke is not less beneficial than routine rehabilitation and can be a rehabilitation service of choice if follow-up at 6 and 12 months confirms the suggested effectiveness and considerable reduction in use of health care Objectives : There is inconclusive evidence of the effectiveness of stroke rehabilitation by a community stroke team . The aim was to evaluate a specialist multiprofessional team in a community setting . Design : R and omized controlled trial . Setting : Community . Participants : Stroke patients and their informal carers who were referred to receive rehabilitation from a community stroke team . Outcome measures : Barthel Index , Extended Activities of Daily Living Scale ( EADL ) , General Health Question naire ( GHQ-12 ) by patient and carer , Carer Strain Index ( CSI ) , Euroquol , knowledge of stroke and satisfaction with services six months after recruitment . Results : There were no significant differences between patients who received rehabilitation from community stroke team ( n = 189 ) and those who received routine care ( n = 232 ) in their independence in activities of daily living , mood , quality of life or knowledge of stroke . The patients in the community stroke team group were significantly more satisfied with the emotional support they had received ( p < 0.01 ) . There were no significant differences between the groups in satisfaction with practical help or overall satisfaction . Carers of patients in the community stroke team were under significantly less strain than carers in the routine care group ( p < 0.04 ) . Carers of patients in the community stroke team group were significantly more satisfied with their knowledge of stroke ( p < 0.01 ) and were more satisfied overall ( p < 0.01 ) . Conclusions : The patients treated by the community stroke team were more satisfied with the emotional support they received and had equivalent outcomes in terms of independence in activities of daily living and mood . Their carers were under less strain and were more satisfied with their knowledge of stroke recovery , the emotional support they received and overall satisfaction with services . The results support the provision of rehabilitation by a community-based specialist multiprofessional team BACKGROUND AND PURPOSE In an inner-London teaching hospital , a r and omized trial of " conventional " care versus early discharge to community-based therapy found no significant differences in clinical outcomes between patient groups . This report examines the economic consequences of the alternative strategies . METHODS One hundred sixty-seven patients received the early discharge package , and 164 received conventional care . Patient utilization of health and social services was recorded over a 12-month period , and cost was determined using data from provider departments and other published sources . RESULTS Inpatient stay after r and omization was 12 days ( intervention group ) versus 18 days ( controls ) ( P=0.0001 ) . Average units of therapy per patient were as follows : physiotherapy , 22.4 ( early discharge ) versus 15.0 ( conventional ) ( P=0.0006 ) ; occupational therapy , 29.0 versus 23.8 ( P=0.002 ) ; speech therapy , 13 . 7 versus 5.8 ( P=0.0001 ) . The early discharge group had more annual hospital physician contacts ( P=0.015 ) and general practitioner clinic visits ( P=0.019 ) but fewer incidences of day hospital attendance ( P=0.04 ) . Other differences in utilization were nonsignificant . Average annual costs per patient were pound sterling 6800 ( early discharge ) and pound sterling 7432 ( conventional ) . The early discharge group had lower inpatient costs per patient ( pound sterling 4862 [ 71 % of total cost ] versus pound sterling 6343 [ 85 % ] for controls ) but higher non-inpatient costs ( pound sterling 1938 [ 29 % ] versus pound sterling 1089 [ 15 % ] ) . Further analysis demonstrated that early discharge is unlikely to lead to financial savings ; its main benefit is to release capacity for an expansion in stroke caseload . CONCLUSIONS Overall results of this trial indicate that early discharge to community rehabilitation for stroke is cost-effective . It may provide a means of addressing the predicted increase in need for stroke care within existing hospital capacity BACKGROUND AND PURPOSE Organized acute stroke treatment reduces mortality , functional deficits , and the need of institutionalization after stroke . It is largely unknown whether the effects of treatment are due to early or subacute efforts . The aim of this r and omized , controlled study was to test the hypothesis that rehabilitation of stroke patients in the subacute phase in a hospital rehabilitation unit is beneficial in reducing death and dependency and increasing health-related quality of life . METHODS 251 patients initially treated in the hospital were r and omized to subacute rehabilitation in a hospital rehabilitation unit ( n = 127 ) or to the health services in the municipality ( n = 124 ) and were followed up for 7 months . RESULTS The combined outcome of patients being dead or dependent ( Barthel Index score of < 75 ) was 23 % in the hospital group and 38 % in the municipality group ( P=.01 ) . Seven-month survival rates were 90.6 % and 83.9 % ( P=.11 ) , respectively . Dependency in activities of daily living was 12.6 % in the hospital group and 25.0 % in the municipality group ( P=.07 ) . Patients with a BI score of < 50 before rehabilitation had significantly better outcome in the hospital rehabilitation unit , with fewer patients becoming dependent ( P=.005 ) and patients having higher Sc and inavian Stroke Scale ( P=.026 ) and BI scores ( P=.005 ) . No significant differences in health-related quality of life were found . Many patients treated in the municipalities ( 30 % ) did not receive any organized rehabilitation in this study . CONCLUSIONS Subacute rehabilitation of stroke patients in a hospital-based rehabilitation unit improves outcome . Patients with moderate or severe stroke appear to benefit most We previously conducted a r and omized controlled trial in which early supported discharge from the Department of Neurology at Huddinge Hospital in southwest Stockholm with continuity of rehabilitation at home ( n = 41 ) was compared to routine rehabilitation services ( n = 40 ) for moderately disabled selected stroke patients . No statistical significant differences were found in patient outcome at 3 or 6 months , but a moderately positive effect in the home rehabilitation group was suggested . In the present study we evaluated re source utilization of health and social care , impact on family caregivers during 6 months after acute stroke and patient satisfaction . A 50 % reduction in total hospitalization ( initial and recurrent ) was observed , from 30 days in the routine rehabilitation group to 15 days in the home rehabilitation group ( p < 0.001 ) . After discharge , the mean number of home visits in the home rehabilitation group was 12 . In total , the routine rehabilitation group had a higher frequency of therapy contacts and daycare in outpatient care . Seventy-eight percent received help from a family caregiver in activities of daily living , yet only 15 % had formal home help service . No major differences were found in use of home help service or impact on family caregivers in the form of time devoted to helping the patient or subjective well-being of spouses as per Sickness Impact Profile . Patient satisfaction was in favour of the home rehabilitation group , but a significant difference was only found in active participation in rehabilitation programme planning . In conclusion , early supported discharge with continuity of rehabilitation at home , using goal -directed functional activities based on the patient 's personal interests , should be the rehabilitation service of choice for moderately disabled stroke patients fulfilling certain criteria , provided that further evaluation during the first year after stroke reveals no great changes in outcome or re source use . More research into the effectiveness and cost implication s of early supported discharge with continuity of rehabilitation at home is needed in other parts of Sweden and in other countries before it can be asserted that the conclusions drawn from this study are applicable elsewhere Hospital-at-Home schemes have been cl aim ed to hasten the discharge of elderly orthopaedic patients , and are becoming increasingly popular with health service managers . In an attempt to measure the benefits of such a scheme when applied to elderly medical patients , we prospect ively r and omized 60 consecutive referrals of patients approaching discharge either to the Hospital-at-Home ( HAH ) rehabilitation team , or to conventional discharge ( CD ) preparation and domiciliary support . Patients allocated to HAH were discharged on average 5 days earlier than CD , while 64 % of each group remained at home during 6 months follow-up . Improvements in independence were modest , and similar in the two groups , though a trend favoured HAH Background Stroke causes lasting disability and the burden of stroke is expected to increase substantially during the next decades . Optimal rehabilitation is therefore m and atory . Early supported discharge ( ESD ) has previously shown beneficial , but all major studies were carried out more than ten years ago . We wanted to implement and study the results of ESD in our community today with comparisons between ESD and treatment as usual , as well as between two different ESD models . Methods Patients with acute stroke were included during a three year period ( 2008–11 ) in a r and omised controlled study comparing two different ESD models to treatment as usual . The two ESD models differed by the location of treatment : either in a day unit or in the patients ’ homes . Patients in the ESD groups were followed by a multi-disciplinary ambulatory team in the stroke unit and discharged home as early as possible . The ESD models also comprised treatment by a multi-disciplinary community health team for up to five weeks and follow-up controls after 3 and 6 months . Primary outcome was modified Rankin Scale ( mRS ) at six months . Results Three-hundred- and -six patients were included . mRS scores and change scores were non-significantly better in the two ESD groups at 3 and 6 months . Within-group improvement from baseline to 3 months was significant in the ESD 1 ( p = 0.042 ) and ESD 2 ( p = 0.001 ) groups , but not in the controls . More patients in the pooled ESD groups were independent at 3 ( p = 0.086 ) and 6 months ( p = 0.122 ) compared to controls and there also was a significant difference in 3 month change score between them ( p = 0.049 ) . There were no differences between the two ESD groups . Length of stay in the stroke unit was 11 days in all groups . Conclusions Patients in the ESD groups tended to be more independent than controls at 3 and 6 months , but no clear statistically significant differences were found . The added effect of supported discharge and improved follow-up seems to be rather modest . The improved stroke treatment of today may necessitate larger patient sample s to demonstrate additional benefit of ESD . Clinical trial registration Unique identifier : Background and Purpose — To compare a community-based multidisciplinary stroke team ( CST ) approach with hospital-based rehabilitation in terms of hospital stay , functioning , quality of life , and service use and costs . Methods — Stroke patients who met pre-agreed criteria were allocated r and omly to the CST service ( n=59 ) or to usual inpatient rehabilitation and follow-up care ( n=54 ) . Assessment s were completed at r and omization and 12 months later . Caregiver strain and satisfaction ( n=55 ) were also assessed . Cost data were collected for a sub sample of 38 patients . Results — Almost 80 % of surviving patients ( n=691 ) were discharged home and a small number ( n=55 ) were readmitted . Approximately 17 % ( 113/649 ) were r and omized . There were no statistically significant differences in hospital duration , costs , or outcome measures at baseline and 12 months except for higher satisfaction reported by CST patients . Overall , both groups recorded improvement in most domains over time . Carers reported a high level of satisfaction although the level of strain among carers is cause for concern . The community group ( n=18 ) cost less than the hospital group ( n=20 ) . Conclusions — A mixed model of hospital-based and community-based rehabilitation services is likely to lead to increased patient choice and satisfaction and a potential reduction in bed pressures for less severe stroke patients Background Stroke is the disease with the highest costs for hospital care and also after discharge . Early supported discharge ( ESD ) has shown to be efficient and safe and the best results with well-organised discharge teams and patients with less severe strokes . The aim is to investigate if very early supported discharge ( VESD ) for stroke patients in need for on-going individualised rehabilitation at home is useful for the patient and cost effective . Methods / design A r and omized controlled trial comparing VESD with ordinary discharge . Inclusion criteria : confirmed stroke , > 18 years of age , living within 30 min from the stroke unit , on day 2 0–16 points on the National institute of health stroke scale ( NIHSS ) and 50–100 points on the Barthel Index ( BI ) , with BI 100 then the patient can be included if the Montreal Cognitive Assessment is < 26 . Exclusion criteria are : NIHSS > 16 , BI < 50 , life expectancy < 1 year , inability to speak or to communicate in Swedish . The inclusion occurs on day 4 and in block r and omization of 20 and with blinded assessor . Primary outcome : levels of anxiety and depression . Secondary outcomes : independence , security , level of function , quality of health , needs of support in activities of daily living and caregiver burden . Power calculation is based on the level of anxiety and with a power of 80 % , p-value 0.05 ( 2 sided test ) 44 persons per group are needed . Data is gathered on co-morbidity , re-entry to hospital , mortality and a health economic analysis . Interviews will be accomplished with a strategic sample of 15 patients in the intervention group before discharge , within two weeks after homecoming and 3 months later . Interviews are also planned with 15 relatives in the intervention group 3 months after discharge . Discussion The ESD studies in the Cochrane review present hospital stays of a length that no longer exist in Sweden . There is not yet , to our knowledge , any study of early supported discharge with present length of hospital stay . Thus it is not clear if home rehabilitation nowadays without risks , is cost effective , or with the same patient usefulness as earlier studies .Trial registration Clinical Trials.gov Background Globally , most strokes occur in low- and middle-income countries , such as India , with many affected people having no or limited access to rehabilitation services . Western models of stroke rehabilitation are often unaffordable in many population s but evidence from systematic review s of stroke unit care and early supported discharge rehabilitation trials suggest that some components might form the basis of affordable interventions in low-re source setting s. We describe the background , history and design of the ATTEND trial , a complex intervention centred on family-led stroke rehabilitation in India . Methods / design The ATTEND trial aims to test the hypothesis that a family-led caregiver-delivered home-based rehabilitation intervention , design ed for the Indian context , will reduce the composite poor outcome of death or dependency at 6 months after stroke , in a multicentre , individually r and omized controlled trial with blinded outcome assessment , involving 1200 patients across 14 hospital sites in India . Discussion The ATTEND trial is testing the effectiveness of a low-cost rehabilitation intervention that could be widely generalizable to other low- and middle-income countries . Trial registration Clinical Trials Registry-India CTRI/2013/04/003557 . Australian New Zeal and Clinical Trials Registry ACTRN12613000078752 . Universal Trial Number U1111 - 1138 - 6707 Background and Purpose Several trials have shown that stroke unit care improves outcome for stroke patients . The aim of the present trial was to evaluate the effects of an extended stroke unit service ( ESUS ) , with early supported discharge , cooperation with the primary healthcare system , and more emphasis on rehabilitation at home as essential elements . Methods In a r and omized , controlled trial , 160 patients with acute stroke were allocated to the ESUS and 160 to the ordinary stroke unit service ( OSUS ) . The primary outcome was the proportion of patients who were independent as assessed by the modified Rankin Scale ( RS ) ( RS ≤2=global independence ) and independent in activities of daily living ( ADL ) as assessed by Barthel Index ( BI ) ( BI ≥95=independent in ADL ) after 26 weeks . Secondary outcomes were RS and BI scores after 6 weeks ; the proportion of patients at home , in institutions , and deceased after 6 and 26 weeks ; and the length of stay in institutions . Results After 26 weeks , 65.0 % in the ESUS versus 51.9 % in the OSUS group showed global independence ( RS ≤2 ) ( P= 0.017 ) , while 60.0 % in the ESUS versus 49.4 % in the OSUS group were independent in ADL ( BI ≥95 ) ( P = 0.056 ) . The odds ratios for independence ( ESUS versus OSUS ) were as follows : RS , 1.72 ( 95 % CI , 1.10 to 2.70 ) ; BI , 1.54 ( 95 % CI , 0.99 to 2.39 ) . At 6 weeks , 54.4 % of the ESUS group and 45.6 % of the OSUS group were independent according to RS ( P = 0.118 ) , and 56.3 % versus 48.8 % were independent according to BI ( P = 0.179 ) . The proportion of patients at home after 6 weeks was 74.4 % for ESUS and 55.6 % for OSUS ( P = 0.0004 ) , and the proportion in institutions was 23.1 % versus 40.0 % , respectively ( P = 0.001 ) . After 26 weeks , 78.8 % in the ESUS group versus 73.1 % in the OSUS were at home ( P = 0.239 ) , while 13.1 % versus 17.5 % were in institutions ( P = 0.277 ) . The mortality in the 2 groups did not differ . Average lengths of stay in an institution were 18.6 days in the ESUS and 31.1 days in the OSUS group ( P = 0.0324 ) . Conclusions An ESUS with early supported discharge seems to improve functional outcome and to reduce the length of stay in institutions compared with traditional stroke unit care Background Several systematic review s have shown that additional exercise therapy has a positive effect on functional outcome after stroke . However , there is an urgent need for re source -efficient methods to augment rehabilitation services without increasing health care costs . Asking informal caregivers to do exercises with their loved ones , combined with e-health services may be a cost-effective method to promote early supported discharge with increased functional outcome .The primary aim of the CARE4STROKE study is to evaluate the effects and cost-effectiveness of a caregiver-mediated exercises program combined with e-health services after stroke in terms of self-reported mobility and length of stay . Methods An observer-blinded r and omized controlled trial , in which 66 stroke- patients admitted to a hospital stroke unit , rehabilitation center or nursing home are r and omly assigned to either 8 weeks of the CARE4STROKE program in addition to usual care ( i.e. , experimental group ) or 8 weeks of usual care alone ( i.e. , control group ) . The CARE4STROKE program is compiled in consultation with a trained physical therapist . A tablet computer is used to present video-based exercises for gait and gait-related activities in which a caregiver acts as an exercise coach . Primary outcomes are the mobility domain of the Stroke Impact Scale and length of stay . Secondary outcomes are the other domains of the Stroke Impact Scale , motor impairment , strength , walking ability , balance , mobility , ( Extended ) Activities of Daily Living , psychosocial functioning , self-efficacy , fatigue , health-related quality of life of the patient as well as the experienced strain , psychosocial functioning and quality of life of the caregiver . An economic evaluation will be conducted from the societal and health care perspective . Discussion The main aspects of the CARE4STROKE program are 1 ) increasing intensity of training by doing exercises with a caregiver in addition to usual care and 2 ) e-health support . We hypothesize this program leads to better functional outcome and early supported discharge , result ing in reduced costs . Trial registration The study is registered in the Dutch trial register as NTR4300 , registered 2 December 2013 Abstract More knowledge is needed about how different rehabilitation models in the municipality influence stroke survivors ’ ability in activities of daily living ( ADL ) . Objectives : To compare three models of outpatient rehabilitation ; early supported discharge ( ESD ) in a day unit , ESD at home and traditional treatment in the municipality ( control group ) , regarding change in ADL ability during the first three months after stroke . Methods : A group comparison study was design ed within a r and omized controlled trial . Included participants were tested with the Assessment of Motor and Process Skills ( AMPS ) at baseline and discharged directly home . Primary and secondary outcomes were the AMPS and the modified Rankin Scale ( mRS ) . Results and conclusions : Included were 154 participants ( 57 % men , median age 73 years ) , and 103 participants completed the study . There were no significant group differences in pre – post changed ADL ability measured by the AMPS . To find the best rehabilitation model to improve the quality of stroke survivors ’ motor and process skills needs further research . Patients participating in the ESD rehabilitation models were , compared with traditional treatment , significantly associated with improved ADL ability measured by the mRS when controlling for confounding factors , indicating that patients with social needs and physical impairment after stroke may benefit from ESD rehabilitation models Objectives : The aim of the present trial was to compare the effects of an extended stroke unit service ( ESUS ) with the effects of an ordinary stroke unit service ( OSUS ) on long-term quality of life ( QoL ) . Design : One year follow-up of a r and omized controlled trial with 320 acute stroke patients allocated either to OSUS ( 160 patients ) or ESUS ( 160 patients ) with early supported discharge and follow-up by a mobile team . The intervention was a mobile team and close co-operation with the primary health care service . All assessment s were blinded . Main outcome measure : Primary outcome of QoL in this paper was measured by the Nottingham Health Profile ( NHP ) at 52 weeks . Secondary outcomes measured at 52 weeks were differences between the groups measured by the Frenchay Activity Index , Montgomery-A ° sberg Depression Scale , Mini-Mental State Score and the Caregivers Strain Index . Results : The ESUS group had a significantly better QoL ( mean score 78.9 ) assessed by global NHP after one year than the OSUS group ( mean score 75.2 ) ( p -0.048 ) . There were no significant differences between the groups in the secondary outcomes , but a trend in favour of ESUS . Caregivers Strain Index showed a mean score of 23.3 in the ESUS group and 22.6 in the OSUS group ( p -0.089 ) . Conclusion : It seems that stroke unit treatment combined with early supported discharge in addition to reducing the length of hospital stay can improve long-term QoL. However , similar trials are necessary to confirm the benefit of this type of service Background and Purpose : This study sought to evaluate early supported discharge and continued rehabilitation at home after stroke , at a minimum of 6 months after the intervention , in terms of patient outcome , re source use and health care cost . Methods : Eighty-three patients , moderately impaired 5–7 days after acute stroke , were included in a r and omized controlled trial , 42 being allocated to the intervention and 41 to routine rehabilitation . One-year follow-up of patient outcome included mortality , motor capacity , dysphasia , activities of daily living , social activities , perceived dysfunction , and self-reported falls . Re source use over 12 months included inpatient hospital care , outpatient health care , use of health-related services , informal care , and cost of health care . Results : On univariate analysis there was no difference in patient outcome . Multivariate regression analysis showed that intervention had a significant effect on independence in activities of daily living . A significant difference in inpatient hospital care , initial and recurrent , was observed , with a mean of 18 ( intervention ) versus 33 days ( control ) ( p = 0.002 ) . Further significant differences were that the control group registered more outpatient visits to hospital occupational therapists ( p = 0.02 ) , private physical therapists ( p = 0.03 ) and day-hospital attendance ( p = < 0.001 ) , while the intervention group registered more visits to nurses in primary care ( p = 0.03 ) and home rehabilitation ( p = < 0.001 ) . Other differences in outcomes or re source utilization were nonsignificant . Conclusion : In Sweden , early supported discharge with continued rehabilitation at home proved no less beneficial as a rehabilitation service , and provided care and rehabilitation for 5 moderately disabled stroke patients over 12 months after stroke onset for the cost of 4 in routine rehabilitation Objective : To establish the feasibility and method of evaluation of an early supported hospital discharge policy for patients with acute stroke . Design : A r and omized controlled trial comparing an early supported discharge service to conventional care . Setting : Three acute hospitals in Newcastle upon Tyne . Subjects : Ninety-two eligible patients with acute stroke admitted between 1 February 1995 and 31 January 1996 . Main outcome measures : Placement , length of stay , readmission rates , mortality , functional ability ( Nottingham Extended Activities of Daily Living ( ADL ) Scale ) , h and icap ( Oxford H and icap Scale ) , global health status ( Dartmouth Coop Function Charts ) and carer stress ( General Health Question naire 30 item ) . Results : The median length of stay for patients r and omized to early supported discharge was 13 days compared to 22 days in the conventional care group ( p = 0.02 ) . The median Barthel ADL Index at seven days post stroke of patients r and omized to early supported discharge was 15 , and 13 for those r and omized to conventional care ( NS ) . At three months post stroke the median Nottingham EADL score of patients r and omized to early supported discharge was 10 compared to 7 for those who received conventional care ( NS ) . There were no statistically significant differences in the global health status of patients or carer stress . Conclusion : An early supported discharge service following acute stroke with individualized rehabilitation in the community is feasible and can be evaluated by a r and omized controlled trial but a larger multicentre trial is needed before such a service is widely adopted BACKGROUND Early supported discharge ( ESD ) with continued rehabilitation at home has shown a beneficial effect on extended activities of daily living 5 years after stroke . The long-term effect of ESD on re source use has not been explored . METHODS At 5 years , 54 patients with mild to moderate disability , enrolled in a r and omized controlled trial of ESD , were followed up . Data were collected from a county register and by interviewing the patient or the patient 's spouse . RESULTS There were differences in mean length of hospitalization , 51 versus 32 days ( P = .02 ) . There was no significant difference between the groups in regard to total outpatient rehabilitation , ESD visits included , but there was a difference in where the services were obtained . The ESD group had more rehabilitation at home ( ESD service ) and the control group had more outpatient rehabilitation ( P = .04 ) , including physiotherapy in primary care ( P = .05 ) . There were no other differences . CONCLUSION We conclude that , 5 years after stroke , our ESD service was favorable with regard to re source use Background The aim of this pilot study was to determine the feasibility of a multicenter , r and omized , controlled trial in India of a family-led , trained caregiver-delivered , home-based rehabilitation intervention vs. routine care . Methods A prospect i ve , r and omized ( within seven-days of hospital admission ) , blinded outcome assessor , controlled trial of structured home-based rehabilitation delivered by trained and protocol -guided family caregivers ( intervention ) vs. routine care alone ( control ) was conducted in patients with residual disability . Key feasibility measures were recruitment , acceptance and adherence to assessment procedures , and follow-up of participants over six-months . CTRI/2014/10/005133 . Results A total of 104 patients from the stroke unit at Christian Medical College , Ludhiana were recruited over nine-months . Recruitment was feasible and accepted by patients and their carers . Important observations were made regarding potential unblinding of the participants , contamination of therapy between the r and omized groups , organization of home visits , and re sources required for a multicenter study . Conclusion The pilot study established the feasibility of conducting a large-scale study of family-led , trained caregiver-delivered , home-based stroke rehabilitation in a low re source setting . The main phase of the trial ‘ ATTEND ’ is currently underway in over 10 centers in India Background : An early supported discharge service ( ESD ) appears to be a promising alternative to conventional care . The aim of this trial was to compare the use of health services and costs with traditional stroke care during a one-year follow-up . Methods : Three hundred and twenty patients were r and omly allocated either to ordinary stroke unit care or stroke unit care combined with ESD which was coordinated by a mobile team . The use of all health services was recorded prospect ively ; its costs were measured as service costs and represent a combination of calculated average costs and tariffs . Hospital expenses were measured as costs per inpatient day and adjusted for the DRG . Results : There was a reduction in average number of inpatient days at 52 weeks in favour of the ESD group ( p = 0.012 ) , and a non-significant reduction in total mean service costs in the ESD group ( EUR 18,937/EUR 21,824 ) . ESD service seems to be most cost-effective for patients with a moderate stroke . Conclusion : Acute stroke unit care combined with an ESD programme may reduce the length of institutional stay without increasing the costs of outpatient rehabilitation compared with traditional stroke care BACKGROUND The effects of residence in an acute geriatrics-based ward ( AGW ) with emphasis on early rehabilitation and discharge planning for older patients with acute medical illnesses were assessed . Outcome and use of re sources were compared with those of patients treated in general medical wards ( MWs ) . A per- protocol rather than intention-to-treat analysis was performed . METHODS A r and omized trial with 3-months follow-up . A total of 190 patients aged 70 years and older were r and omized to an acute geriatrics-based ward , and 223 patients were r and omized to general medical wards . RESULTS The two groups were comparable at inclusion . However , after care in the AGW , 71 % of patients could be discharged directly home compared with 64 % of those treated in MWs ( relative risk 1.17 ; 95 % CI , 0.93 - 1.49 ) . The length of stay was shorter in the AGW ( mean 5.9 vs 7.3 days ; P = .002 ) . The proportion of patients in geriatric or other hospital wards or in nursing homes did not differ , but the proportion of AGW patients in sheltered living tended to be lower ( P = .085 ) . At the follow-up , case fatality , ADL function , psychological well-being , need for daily personal assistance , drug consumption , need for readmission to hospital , and total health care costs after discharge did not differ between the two groups . Poor global outcome was observed in 37 % of AGW and 34 % of MW patients . CONCLUSIONS A geriatric approach with greater emphasis on early rehabilitation and discharge planning in the AGW shortened the length of hospital stay and may have reduced the need for long-term institutional living . This occurred despite patients in an acute geriatric ward not having better medical or functional outcome than older acute patients treated in general medical wards Rationale As a result of demographic changes with a presumed rapidly increasing number of older people during the coming decades , a strong increase in the incidence and prevalence of stroke should be expected . Early supported discharge implies that the patients are discharged to their homes as soon as feasible and that rehabilitative treatment is offered after the discharge , with the patients being home-dwelling . This has proved beneficial in previous studies . Aims The main objective of this study is to further characterize the important components of early supported discharge and to confirm superiority of early supported discharge over conventional treatment . The secondary aim will be to compare two different early supported discharge schemes . These early supported discharge schemes are composed of intensive rehabilitation treatment given by a multidisciplinary team in a day unit and , alternatively , the same treatment given in the patients ' homes . Design The study is conducted as a r and omized controlled trial with three arms : two different forms of early supported discharge and a control arm with conventional treatment . Patients with acute stroke admitted to our hospital 's stroke unit and living in the Municipality of Bergen are considered for inclusion . A total of 350 stroke patients are expected . Study outcomes Primary outcome is modified Rankin Scale six-months after inclusion . Secondary outcomes include Barthel Index and National Institute of Health Stroke Scale at several points in time after inclusion , as well as many other schemes , question naires and physical tests . The study is registered in Clinical Trials.gov registration number NCT00771771 Background In low- and middle-income countries , few patients receive organized rehabilitation after stroke , yet the burden of chronic diseases such as stroke is increasing in these countries . Affordable models of effective rehabilitation could have a major impact . The ATTEND trial is evaluating a family-led caregiver delivered rehabilitation program after stroke . Objective To publish the detailed statistical analysis plan for the ATTEND trial prior to trial unblinding . Methods Based upon the published registration and protocol , the blinded steering committee and management team , led by the trial statistician , have developed a statistical analysis plan . The plan has been informed by the chosen outcome measures , the data collection forms and knowledge of key baseline data . Results The result ing statistical analysis plan is consistent with best practice and will allow open and transparent reporting . Conclusions Publication of the trial statistical analysis plan reduces potential bias in trial reporting , and clearly outlines pre-specified analyses . Clinical Trial Registration s India CTRI/2013/04/003557 ; Australian New Zeal and Clinical Trials Registry ACTRN1261000078752 ; Universal Trial Number U1111 - 1138 - 6707 OBJECTIVES To evaluate whether home treatment of elderly patients with acute uncomplicated first ischemic stroke is associated with different mortality rates and clinical outcomes from those of patients treated on a general medical ward ( GMW ) . DESIGN R and omized , controlled , single-blind trial . SETTING S. Giovanni Battista Hospital of Turin . PARTICIPANTS One hundred twenty elderly patients admitted to the emergency department of the hospital with first acute ischemic stroke were r and omized to home treatment from a geriatric home hospitalization service ( GHHS ) or to GMW treatment . MEASUREMENT Main outcome was cumulative survival at 6 months in the two groups . Residual functional impairment , neurological deficit , depression , morbidity , and admission to rehabilitation and long-term care facilities were considered as secondary outcomes in survivors . RESULTS One hundred twenty patients ( mean age 82 ; 54 men and 66 women ) were enrolled ( 60 in each study arm ) . The cumulative proportion of cases surviving at 6 months was 0.65 in the GHHS group and 0.60 in GMW group ( log-rank test P=.53 ) . Functional and neurological parameters were significantly improved in both GHHS and GMW patients , without significant differences between the two groups . Depression score was significantly better in home-treated patients ( P<.001 ) , who were more likely to remain at home at 6 months than hospital-treated patients and had a lower rate of select medical complications . CONCLUSION Home-treated elderly patients with ischemic stroke have better depressive scores and lower rates of admission to nursing homes . These results should prompt further studies to evaluate home hospitalization for elderly stroke patients Rationale Stroke is the leading cause of death and disability in rural China . For stroke patients residing in re source -limited rural areas , secondary prevention and rehabilitation are largely unavailable , and where present , are far below evidence -based st and ards . Aim This study aims to develop and implement a simplified stroke rehabilitation program that utilizes nurses and family caregivers for service delivery , and evaluate its feasibility and effectiveness in rural China . Methods and design This 2-year r and omized controlled trial is being conducted in 2–3 county hospitals located in northwest , northeast , and southwest China . Eligible and consenting stroke in patients ( 200 in total ) have been recruited and r and omized into either a control or intervention group . Nurses in the county hospital are trained by rehabilitation specialists and in turn train the family caregivers in the intervention group . They also provide telephone follow-up care three times post discharge . The recruitment , baseline , intervention , follow-up care , and evaluation are guided by the RECOVER mobile phone app specifically design ed for this study . Study outcome The primary outcome is patients ’ Barthel Index ( activities of daily living : mobility , self-care , and toileting ) at 6 months . Process and economic evaluation will also be conducted . Discussion The results of our study will generate initial high- quality evidence to improve stroke care in re source -scarce setting s. If proven effective , this innovative care delivery model has the potential to improve the health and function of stroke patients , relieve caregiver burden , guide policy-making , and advance translational research in the field of stroke care BACKGROUND AND PURPOSE Because stroke management is aim ed at facilitating community reintegration , it would be logical that the sooner the patient can be discharged home , the sooner reintegration can commence . The purpose of this study was to determine the effectiveness of prompt discharge combined with home rehabilitation on function , community reintegration , and health-related quality of life during the first 3 months after stroke . METHODS A r and omized trial was carried out involving patients who required rehabilitation services and who had a caregiver at home . When medically ready for discharge , persons with stroke were r and omized to either the home intervention group ( n=58 ) or the usual care group ( n=56 ) . The home group received a 4-week , tailor-made home program of rehabilitation and nursing services ; persons r and omized to the usual care group received services provided through a variety of mechanisms , depending on institutional , care provider , and personal preference . The main outcome measure was the Physical Health component of the Measuring Outcomes Study Short-Form-36 ( SF-36 ) . Associated outcomes measures included the Timed Up & Go ( TUG ) , Barthel Index ( BI ) , the Older Americans Re source Scale for instrumental activities of daily living ( OARS-IADL ) , Reintegration to Normal Living ( RNL ) , and the SF-36 Mental Health component . RESULTS The total length of stay for the home group was , on average , 10 days , 6 days shorter than that for the usual care group . There were no differences between the 2 groups on the BI or on the TUG at either 1 or 3 months after stroke ; however , there was a significantly beneficial impact of the home intervention on IADL and reintegration ( RNL ) . By 3 months after stroke , the home intervention group showed a significantly higher score on the SF-36 Physical Health component than the usual care group . The total number of services received by the home group was actually lower than that received by the usual care group . CONCLUSIONS Prompt discharge combined with home rehabilitation appeared to translate motor and functional gains that occur through natural recovery and rehabilitation into a greater degree of higher-level function and satisfaction with community reintegration , and these in turn were translated into a better physical health Abstract Objective : To assess the clinical effectiveness of an early discharge policy for patients with stroke by using a community based rehabilitation team . Design : R and omised controlled trial to compare conventional care with an early discharge policy . Setting : Two teaching hospitals in inner London . Subjects : 331 medically stable patients with stroke ( mean age 71 ) who lived alone and were able to transfer independently or who lived with a resident carer and were able to transfer with help . Interventions : 167 patients received specialist community rehabilitation for up to 3 months after r and omisation . 164 patients continued with conventional hospital and community care . Main outcome measures : Barthel score at 12 months . Secondary outcomes measured impairment with motoricity index , minimental state examination , and Frenchay aphasia screening test ; disability with the Rivermead activity of daily living scales , hospital anxiety and depression scale , and 5 m walk ; h and icap with the Nottingham health profile ; carer stress with caregiver strain index and patient and carer satisfaction . The main process measure was length of stay after r and omisation . Results : One year after r and omisation no significant differences in clinical outcomes were found apart from increased satisfaction with hospital care in the community therapy group . Length of stay after r and omisation in the community therapy group was significantly reduced ( 12 v 18 days ; P<0.0001 ) . Patients with impairments were more likely to receive treatment in the community therapy group . Conclusions : Early discharge with specialist community rehabilitation after stroke is feasible , as clinical ly effective as conventional care , and acceptable to patients . Considerable reductions in use of hospital beds are achievable . Key messages Early discharge from hospital after stroke with specialist rehabilitation at home is feasible without an increase in readmission rates or stress to carers This r and omised controlled trial shows this method to be as effective as conventional care when assessed with a range of measures of impairment , disability , h and icap , carer stress , and patient and carer satisfaction at 1 year Significant reductions in bed usage can be achieved by the provision of a community rehabilitation team with no significant increase in rehabilitation Objective : An intensified transition concept between neurological inpatient rehabilitation and home care was investigated for effects on the functional status of stroke patients and the physical and emotional health of their carers . Design : Controlled clinical trial allocating patients to intervention group ( intensified transition on ward II ) or control group ( st and ard transition on ward I ) ; patients were allocated to whichever ward had a vacancy . Follow-up assessment was carried out six months after discharge . Subjects : Seventy-one patients and their family carers were included , of which nine cases dropped out . Therefore 62 stroke patients with persisting disability and their family carers were available for assessment at follow-up - 33 patients in the intervention group , 29 patients in the control group . Intervention : The intensified transition concept consisted of therapeutic weekend care , bedside teaching and structured information for relatives during the second phase of the rehabilitation . Main measures : Patients were assessed with the Barthel Index , Functional Independence Measure , Ashworth Spastic Scale , Frenchay Arm Test , and Timed Up and Go Test . The carers completed SF-36 , and were assessed using the Giessen Symptom List , Depression Scale and Burden Scale for Family Caregivers . Results : The intensified transition did not lead to significant change in the functional status of the patients or in the physical and emotional health of the family carers . Within the first four weeks after discharge , the patients in the intervention group had fewer new illnesses . In the observation period the use of outpatient care services was more frequent in the intervention group than in the control group . Conclusion : Even though there are few differences of moderate intensity between the two groups the intensified transition programme does not affect either the functional status of the stroke patients or the health of the carers A r and omised controlled trial was conducted to assess whether a single intervention by a health visitor reduced the unplanned re-admission of elderly people discharged from geriatric wards . Two hundred and four consecutive discharges from geriatric wards were r and omly allocated to receive either a single visit from the health visitor at 72 h in addition to normal follow-up services or to a control group receiving the normal follow-up services . The primary outcome measure was the unplanned re-admissions over the following 6 months . There were 40 cases and 43 control patients with unplanned re-admissions in the first 6 months . The total lengths of the unplanned re-admissions were 1237 days for cases and 1427 for controls , an average of 12.1 days for cases and 14.0 for controls ( 95 % confidence interval -4.9 to 8.7 days , not significant ) . A visit by a health visitor to elderly patients after discharge from geriatric wards is unlikely to be of sufficient benefit to the patients for the service to be funded from a saving in unplanned re-admissions Objective : To evaluate the effect of an extended stroke unit service ( extended service ) , with early supported discharge and co-ordination of further rehabilitation in co-operation with the primary health care system in three rural municipalities . Design : A r and omized controlled trial comparing extended service with ordinary stroke unit service ( ordinary service ) . Subjects : Sixty-two eligible patients with acute stroke living in the rural municipalities of Malvik , Melhus and Klñ bu . Main measures : The primary outcome was the proportion of patients who were independent according to Modified Rankin Scale ( mRS ) ( independence = mRS < 2 ) 52 weeks after onset of stroke . Secondary outcomes were mRS at 6 and 26 weeks and Barthel Index ( BI ) , Nottingham Health Profile ( NHP ) and Caregiver Strain Index ( CSI ) at 6 , 26 and 52 weeks . Mortality and length of stay were registered during the 52 weeks . Results : Twelve patients ( 39 % ) in the extended service group versus 16 patients ( 52 % ) in the ordinary service group were independent according to mRS at 52 weeks ( p= 0.444 ) . The odds ratio for independence ( extended service versus ordinary service ) was 0.33 ( 95 % confidence interval ( CI ) 0.088 –1.234 ) . According to outcome by secondary measures there were no significant differences except less social isolation on NHP in the extended service group at 26 weeks ( p= 0.046 ) . There were no significant differences in length of stay . Conclusion : An extended stroke unit service with early supported discharge seems to have no positive effect on functional outcome for patients living in rural communities , but might give a trend toward better quality of life . There were no significant differences in length of stay In a controlled trial of a home-care service available for the first 6 months after acute stroke , 440 patients received the new service and 417 patients were in the control group . The trial group used more hospital bed days , had a slightly higher admission rate , and did not show better emotional adjustment to stroke than the control group . There was no difference between the 2 groups in stress on relatives . Functional recovery was equal in the 2 groups . A quarter of patients managed at home in each group were severely disabled . Providing a new service does not necessarily alter clinical decisions in the short term , and care should be taken before exp and ing domiciliary services to reduce hospital use This prospect i ve r and omized controlled study was design ed to compare the treatment efficacy , safety and quality of life of ischemic stroke patients treated with conventional ( 10-day ) hospitalization or short ( 3-day ) hospitalization followed by home care treatment . One hundred and two patients with acute ischemic stroke who arrived within 48 h after symptom onset and met the inclusion criteria were studied . Patients were r and omly assigned to either of two groups of treatment . Patients in the ‘ hospitalization ’ group were hospitalized for 10 days , whereas those in the ‘ home care ’ group were admitted only for the first 3 days and were followed at home under the home care program . The baseline characteristics were similar in the two groups . There was no difference in the number of deaths or dependency defined by the Modified Rankin scale more than or equal to 3 between the two groups at 6 months . The relative risk was 0.85 with a 95 % confidence interval between 0.35 and 2.04 . There was also no difference in the number of patients who had good outcome ( NIHSS between 0 and 2 and Barthel index between 75 and 100 ) at 6 months . One patient in the home care group died due to massive intracerebral hemorrhage . Seventy-nine percent of patients in the home care group were satisfied with the home treatment program The Home Treatment Team ( HTT ) , a hospital discharge team for elderly patients , was created to provide practical help and promote independence of patients at home for up to 6 weeks after hospital discharge . Patients were those judged to be at particular risk of failing to resettle , and thus being readmitted to hospital or admitted to a residential or nursing home . An open r and omized controlled trial compared patients receiving the HTT ( n = 29 ) with controls ( n = 25 ) receiving appropriate conventional community services . Fewer HTT patients were readmitted ( four by 6 weeks and nine by 12 weeks ) than controls ( nine by 6 weeks and 14 by 12 weeks , p < 0.05 ) and more were at home at 6 weeks ( 24 , 83 % and 10 , 40 % , p < 0.05 ) , 12 weeks ( 21 , 72 % and 11 , 44 % , p < 0.05 ) and 12 months ( 17 , 58 % and 10 , 40 % , p < 0.05 ) . The HTT group spent fewer days in hospital than controls during 12 weeks ( median difference 34 days , 95 % confidence interval 0 - 75 , p < 0.05 ) and more days at home during 12 months ( 90 ; 247 - 0 , p = 0.02 ) . Neither group showed any significant change in mental state or functional abilities over 12 weeks . Potentially confounding factors were considered insufficient explanation for the difference in outcome between the groups . It is concluded that the HTT was of benefit but the mechanism of its effect was not identified Objective : To evaluate an early home-supported discharge service for stroke patients . Design : We carried out a prospect i ve , r and omised , open-label , blinded-endpoint trial ( allocation ratio of 1:1 ) with patients assigned to either an early home-supported discharge service or usual care . Setting : The study was undertaken in Aveiro , Portugal , between April 2009 and April 2013 . Subjects : We included stroke patients aged 25–85 years admitted to the stroke unit with an initial Functional Independence Measure of up to 100 , who gave informed consent . Interventions : Patients in the early home-supported discharge group began their rehabilitation intervention in the stroke unit and the early home-supported discharge team worked with them at home for a maximum of one month . Patients in the control group received usual services . Main measures : The primary outcome measure was the Functional Independence Measure at six months after stroke . Results : We r and omised 190 patients of whom 34 were lost to follow-up . There were no significant differences ( p > 0.5 ) in the average scores of Functional Independence Measure between the early home-supported discharge ( 69 ±22 ; mean ±SD ) and the control groups ( 71 ±17 ) measured at baseline ; and between the early home-supported discharge ( 107 ±20 ) and the control groups ( 107 ±25 ) measured at six months . The number of individuals with a low Functional Independence Measure score ( < 60 ) in the early home-supported discharge group compared with the control group was higher at admission ( 34/95 vs. 26/95 ) and lower at follow-up ( 2/74 vs. 5/78 ) . Conclusions : It was feasible to implement early home-supported discharge procedures in a Southern European setting , but we have not shown convincing differences in disability at six months BACKGROUND Early supported discharge with continued rehabilitation at home ( ESD ) for patients with mild to moderate impairments has been compared to conventional rehabilitation in a r and omized controlled trial . The aim of this study was to explore changes over time in perceived health status over the five years after stroke onset . METHODS Of 83 patients enrolled in a r and omized controlled trial of ESD compared to conventional rehabilitation , 50 ( home rehabilitation group , n=28 , conventional rehabilitation group , n=22 ) were followed up at one and five years after stroke with regard to perceived health using the Sickness Impact Profile . The Mann Whitney U-test was employed for statistical analysis of differences between the groups at one and five years , and the Wilcoxon sign test for differences within each group between one and five years . RESULTS There was no difference in perceived health between the groups at one or five years after stroke with regard to SIP total and the physical and psychosocial dimensions . Perceived health did not change significantly between one and five years in the home rehabilitation group whereas it had deteriorated significantly in the conventional rehabilitation group ( p=0.05 ) . CONCLUSIONS We conclude that the long term outcome with regard to perceived health status is more favourable after ESD than after conventional rehabilitation . Our results suggest that the environment is a key component to be considered in the rehabilitation process of stroke patients Objective : To evaluate if home-based rehabilitation of in patients improved outcome compared to st and ard care . Design : Interventional , r and omised , safety/efficacy open-label trial . Setting : University hospital stroke unit in collaboration with three municipalities . Subjects : Seventy-one eligible stroke patients ( 41 women ) with focal neurological deficits hospitalised in a stroke unit for more than three days and in need of rehabilitation . Interventions : Thirty-eight patients were r and omised to home-based rehabilitation during hospitalization and for up to four weeks after discharge to replace part of usual treatment and rehabilitation services . Thirty-three control patients received treatment and rehabilitation following usual guidelines for the treatment of stroke patients . Main measures : Ninety days post-stroke the modified Rankin Scale score was the primary endpoint . Other outcome measures were the modified Barthel-100 Index , Motor Assessment Scale , CT-50 Cognitive Test , EuroQol-5D ™ , Body Mass Index and treatment-associated economy . Results : Thirty-one intervention and 30 control patients completed the study . Patients in the intervention group achieved better modified Rankin Scale score ( Intervention median = 2 , IQR = 2 - 3 ; Control median = 3 , IQR = 2–4 ; P=0.04 ) . EuroQol-5D ™ quality of life median scores were improved in intervention patients ( Intervention median = 0.77 , IQR = 0.66–0.79 ; Control median = 0.66 , IQR = 0.56 – 0.72 ; P=0.03 ) . The total amount of home-based training in minutes highly correlated with mRS , Barthel , Motor Assessment Scale and EuroQol-5D ™ scores ( P-values ranging from P<0.00001 to P=0.01 ) . Economical estimations of intervention costs were lower than total costs of st and ard treatment . Conclusion : Early home-based rehabilitation reduced disability and increased quality of life . Compared to st and ard care , home-based stroke rehabilitation was more cost-effective BACKGROUND Organised specialist care for stroke improves outcome , but the merits of different methods of organisation are in doubt . This study compares the efficacy of stroke unit with stroke team or domiciliary care . METHODS A single-blind , r and omised , controlled trial was undertaken in 457 acute-stroke patients ( average age 76 years , 48 % women ) r and omly assigned to stroke unit , general wards with stroke team support , or domiciliary stroke care , within 72 h of stroke onset . Outcome was assessed at 3 , 6 , and 12 months . The primary outcome measure was death or institutionalisation at 12 months . Analyses were by intention to treat . FINDINGS 152 patients were allocated to the stroke unit , 152 to stroke team , and 153 to domiciliary stroke care . 51 ( 34 % ) patients in the domiciliary group were admitted to hospital after r and omisation . Mortality or institutionalisation at 1 year were lower in patients on a stroke unit than for those receiving care from a stroke team ( 21/152 [ 14 % ] vs 45/149 [ 30 % ] ; p<0.001 ) or domiciliary care ( 21/152 [ 14 % ] vs 34/144 [ 24 % ] ; p=0.03 ) , mainly as a result of reduction in mortality . The proportion of patients alive without severe disability at 1 year was also significantly higher on the stroke unit compared with stroke team ( 129/152 [ 85 % ] vs 99/149 [ 66 % ] ; p<0.001 ) or domiciliary care ( 129/152 [ 85 % ] vs 102/144 [ 71 % ] ; p=0.002 ) . These differences were present at 3 and 6 months after stroke . INTERPRETATION Stroke units are more effective than a specialist stroke team or specialist domiciliary care in reducing mortality , institutionalisation , and dependence after stroke |
770 | 25,170,798 | The other studies showed no significant effect for exercise on abstinence . | BACKGROUND Taking regular exercise may help people give up smoking by moderating nicotine withdrawal and cravings , and by helping to manage weight gain .
OBJECTIVES To determine whether exercise-based interventions alone , or combined with a smoking cessation programme , are more effective than a smoking cessation intervention alone . | Background Pharmacotherapies for smoking cessation have not been adequately tested in pregnancy and women are reluctant to use them . Behavioural support alone has a modest effect on cessation rates ; therefore , more effective interventions are needed . Even moderate intensity physical activity ( e.g. brisk walk ) reduces urges to smoke and there is some evidence it increases cessation rates in non-pregnant smokers . Two pilot studies assessed i ) the feasibility of recruiting pregnant women to a trial of physical activity for smoking cessation , ii ) adherence to physical activity and iii ) womens ' perceptions of the intervention . Methods Pregnant smokers volunteered for an intervention combining smoking cessation support , physical activity counselling and supervised exercise ( e.g. treadmill walking ) . The first study provided six weekly treatment sessions . The second study provided 15 sessions over eight weeks . Physical activity levels and continuous smoking abstinence ( verified by expired carbon monoxide ) were monitored up to eight months gestation . Results Overall , 11.6 % ( 32/277 ) of women recorded as smokers at their first antenatal booking visit were recruited . At eight months gestation 25 % ( 8/32 ) of the women achieved continuous smoking abstinence . Abstinent women attended at least 85 % of treatment sessions and 75 % ( 6/8 ) achieved the target level of 110 minutes/week of physical activity at end-of-treatment . Increased physical activity was maintained at eight months gestation only in the second study . Women reported that the intervention helped weight management , reduced cigarette cravings and increased confidence for quitting . Conclusion It is feasible to recruit pregnant smokers to a trial of physical activity for smoking cessation and this is likely to be popular . A large r and omised controlled trial is needed to examine the efficacy of this intervention Aerobic exercise can acutely reduce cigarette cravings during periods of nicotine deprivation . The primary aim of this study was to assess the differential effects of light and vigorous intensity aerobic exercise on cigarette cravings , subjective and physiological reactivity to smoking cues , and affect after overnight nicotine deprivation . A secondary aim was to examine cortisol change as a mediator of the effects of exercise on smoking motivation . 162 ( 55 female , 107 male ) overnight nicotine-deprived smokers were r and omized to one of three exercise conditions : light intensity , vigorous intensity , or a passive control condition . After each condition , participants engaged in a st and ardized cue reactivity assessment . Self-reported urges to smoke , affect , and salivary cortisol were assessed at baseline ( i.e. , before each condition ) , immediately after each condition , and after the cue reactivity assessment . Light and vigorous exercise significantly decreased urges to smoke and increased positive affect , relative to the control condition . In addition , those in the vigorous exercise condition demonstrated suppressed appetitive reactivity to smoking cues , as indexed by the startle eyeblink reflex . Although exercise intensity was associated with expected changes in cortisol concentration , these effects were not related to changes in craving or cue reactivity . Both light and vigorous exercise can reduce general cravings to smoke , whereas vigorous exercise appears especially well-suited for reducing appetitive reactions to cues that may precede smoking . Results did not support exercise-induced cortisol release as a mechanism for these effects Exercise has been hypothesized to curb increases in depressive symptoms often associated with smoking cessation . The relationship between increased fitness and changes in depressive symptoms was examined among 40 women who were abstinent at the end of an 8-week r and omized controlled trial . Participants received group-based , cognitive-behavioral smoking cessation treatment plus either exercise or contact control . All participants completed maximal fitness tests and question naires , including the Centers for Epidemiological Studies Depression Scale at baseline and at post-treatment . Regardless of treatment assignment , women who increased fitness over the 8-week treatment period were more likely to have decreases in depressive symptoms . Results indicate that increased fitness may benefit women by attenuating the depressive symptoms often associated with nicotine withdrawal INTRODUCTION AND OBJECTIVES To assess the efficacy of cardiac rehabilitation with a mixed primary and cardiological care program in patients with low-risk myocardial infa rct ion . PATIENTS AND METHOD The participants in this 12-month prospect i ve study were 153 consecutive patients with low-risk myocardial infa rct ion ( MI ) referred to their primary care center for follow-up care . Of these patients , 113 were referred to a mixed primary and specialized care program that included physical exercise , cardiovascular risk control , an antismoking program , health education talks and psychological evaluation . The other 40 patients served as controls . We analyzed the results after 3 months and 1 year of follow-up . RESULTS There were no differences between the two groups at baseline . After 1 year , improvements were seen in smoking habit ( 4.6 % vs 15.6 % ; P<.05 ) and body mass index ( 26 [ 2 ] vs 29 [ 2 ] ; P<.05 ) . Dyslipidemia , glucose and blood pressure were similar in both groups after follow-up . Greater improvements in the group of patients who participated in the program were seen after 1 year in quality of life ( 78 [ 2 ] vs 91 [ 2 ] ; P<.05 ) , exercise capacity ( 10.3 [ 2 ] vs 8.4 [ 3 ] ; P<<.01 ) and return to active employment ( 84.6 % vs 53.3 % ; P<.05 ) . CONCLUSIONS After 1 year of follow-up , the cardiac rehabilitation program coordinated by cardiological and primary care services for low-risk post-MI patients improved quality of life , and increased exercise tolerance , active employment , and the number of participants who quit smoking . The mixed program also reduced body mass index . These results suggest the need for similar programs Background Many women try to stop smoking in pregnancy but fail . One difficulty is that there is insufficient evidence that medications for smoking cessation are effective and safe in pregnancy and thus many women prefer to avoid these . Physical activity ( PA ) interventions may assist cessation ; however , trials examining these interventions have been too small to detect or exclude plausible beneficial effects . The London Exercise And Pregnant smokers ( LEAP ) trial is investigating whether a PA intervention is effective and cost-effective when used for smoking cessation by pregnant women , and will be the largest study of its kind to date . Methods / design The LEAP study is a pragmatic , multi-center , two-arm , r and omized , controlled trial that will target pregnant women who smoke at least one cigarette a day ( and at least five cigarettes a day before pregnancy ) , and are between 10 and 24 weeks pregnant . Eligible patients are individually r and omized to either usual care ( that is , behavioral support for smoking cessation ) or usual care plus a intervention ( entailing supervised exercise on a treadmill plus PA consultations ) . The primary outcome of the trial is self-reported and biochemically vali date d continuous abstinence from smoking between a specified quit date and the end of pregnancy . The secondary outcomes , measured at 1 and 4 weeks after the quit date , and at the end of pregnancy and 6 months after childbirth , are PA levels , depression , self-confidence , and cigarette withdrawal symptoms . Smoking status will also be self-reported at 6 months after childbirth . In addition , perinatal measures will be collected , including antenatal complications , duration of labor , mode of delivery , and birth and placental weight . Outcomes will be analyzed on an intention-to-treat basis , and logistic regression models used to compare treatment effects on the primary outcome . Discussion This trial will assess whether a PA intervention is effective when used for smoking cessation during pregnancy . Trial registration IS RCT This study examined the relationship between changes in physical activity and changes in smoking among adolescents . We prospect ively examined smoking progression , physical activity , demographic factors , and covariates in 978 high school students participating in a longitudinal cohort study of the predictors of smoking adoption . We used latent growth modeling with the parallel processes smoking progression and physical activity as our method , with smoking progression measured as an ordered categorical variable . Results indicated that higher levels of physical activity reduced the odds of progressing to smoking or a higher level of smoking by nearly 1.5 ( 1.44 ; P < 0.05 ) . No race differences were found . However , being male increased the odds of smoking progression by 1.32 ( P < 0.05 ) . Higher levels of physical activity may reduce the risk of smoking during adolescence . Youth smoking prevention initiatives should incorporate strategies to promote physical activity to prevent smoking experimentation and escalation Abstract The accurate assessment of both tobacco withdrawal and the impact of the nicotine patch on withdrawal may be compromised by attrition of subjects , or by subjects smoking during withdrawal . To reduce these occurrences , 211 participants were provided with intensive cessation counseling while trying to quit smoking with either nicotine ( 21 mg ) or placebo transdermal patches . Subject attrition was low , with 80.5 % of participants continuing through the 5-week study period . Abstinence rates were also high over this period ( 75 % and 61 % in active and placebo groups , respectively ) . In this multisite , double-blind trial , withdrawal severity was assessed using a nine-item daily self-report question naire , and abstinence was confirmed via CO monitoring . Abrupt smoking cessation increased multiple tobacco withdrawal symptoms/signs including craving for cigarettes , irritability , anxiety , appetite , sleep disruption , difficulty concentrating , restlessness , depression , and impatience . Treatment with transdermal nicotine reduced craving for cigarettes , anxiety , irritability , and appetite , as well as weight gain ( 1.85 versus 2.88 kg mean gain over 4 weeks in active and placebo groups , respectively ) Abstract Objective To compare the hazards of cigarette smoking in men who formed their habits at different periods , and the extent of the reduction in risk when cigarette smoking is stopped at different ages . Design Prospect i ve study that has continued from 1951 to 2001 . Setting United Kingdom . Participants 34 439 male British doctors . Information about their smoking habits was obtained in 1951 , and periodically thereafter ; cause specific mortality was monitored for 50 years . Main outcome measures Overall mortality by smoking habit , considering separately men born in different periods . Results The excess mortality associated with smoking chiefly involved vascular , neoplastic , and respiratory diseases that can be caused by smoking . Men born in 1900 - 1930 who smoked only cigarettes and continued smoking died on average about 10 years younger than lifelong non-smokers . Cessation at age 60 , 50 , 40 , or 30 years gained , respectively , about 3 , 6 , 9 , or 10 years of life expectancy . The excess mortality associated with cigarette smoking was less for men born in the 19th century and was greatest for men born in the 1920s . The cigarette smoker versus non-smoker probabilities of dying in middle age ( 35 - 69 ) were 42 % ν24 % ( a twofold death rate ratio ) for those born in 1900 - 1909 , but were 43 % ν 15 % ( a threefold death rate ratio ) for those born in the 1920s . At older ages , the cigarette smoker versus non-smoker probabilities of surviving from age 70 to 90 were 10 % ν 12 % at the death rates of the 1950s ( that is , among men born around the 1870s ) but were 7 % ν 33 % ( again a threefold death rate ratio ) at the death rates of the 1990s ( that is , among men born around the 1910s ) . Conclusion A substantial progressive decrease in the mortality rates among non-smokers over the past half century ( due to prevention and improved treatment of disease ) has been wholly outweighed , among cigarette smokers , by a progressive increase in the smoker ν non-smoker death rate ratio due to earlier and more intensive use of cigarettes . Among the men born around 1920 , prolonged cigarette smoking from early adult life tripled age specific mortality rates , but cessation at age 50 halved the hazard , and cessation at age 30 avoided almost all of it INTRODUCTION Quitting smoking is associated with weight gain , which may threaten motivation to engage or sustain a quit attempt . The pattern of weight gained by smokers treated according to smoking cessation guidelines has been poorly described . We aim ed to determine the weight gained after smoking cessation and its predictors , by smokers receiving individual counseling and nicotine replacement therapies for smoking cessation . METHODS We performed an ancillary analysis of a r and omized controlled trial assessing moderate physical activity as an aid for smoking cessation in addition to st and ard treatment in sedentary adult smokers . We used mixed longitudinal models to describe the evolution of weight over time , thus allowing us to take every participant into account . We also fitted a model to assess the effect of smoking status and reported use of nicotine replacement therapy at each time point . We adjusted for intervention group , sex , age , nicotine dependence , and education . RESULTS In the whole cohort , weight increased in the first 3 months , and stabilized afterwards . Mean 1-year weight gain was 3.3 kg for women and 3.9 kg for men ( p = .002 ) . Higher nicotine dependence and male sex were associated with more weight gained during abstinence . Age over median was associated with continuing weight gain during relapse . There was a nonsignificant trend toward slower weight gain with use of nicotine replacement therapies . CONCLUSION Sedentary smokers receiving a st and ard smoking cessation intervention experience a moderate weight gain , limited to the first 3 months . Older age , male sex , and higher nicotine dependence are predictors of weight gain RATIONALE Attentional bias towards smoking-related cues is increased during abstinence and can predict relapse after quitting . Exercise has been found to reduce cigarette cravings and desire to smoke during temporary abstinence and attenuate increased cravings in response to smoking cues . OBJECTIVE To assess the acute effects of exercise on attentional bias to smoking-related cues during temporary abstinence from smoking . METHOD In a r and omized cross-over design , on separate days regular smokers ( n = 20 ) undertook 15 minutes of exercise ( moderate intensity stationary cycling ) or passive seating following 15 hours of nicotine abstinence . Attentional bias was measured at baseline and post-treatment . The percentage of dwell time and direction of initial fixation was assessed during the passive viewing of a series of paired smoking and neutral images using an Eyelink II eye-tracking system . Self-reported desire to smoke was recorded at baseline , mid- and post-treatment and post-eye-tracking task . RESULTS There was a significant condition x time interaction for desire to smoke , F((1,18 ) ) = 10.67 , P = 0.004 , eta(2 ) = 0.36 , with significantly lower desire to smoke at mid- and post-treatment following the exercise condition . The percentage of dwell time and direction of initial fixations towards smoking images were also reduced significantly following the exercise condition compared with the passive control . CONCLUSION Findings support previous research that acute exercise reduces desire to smoke . This is the first study to show that exercise appears to also influence the salience and attentional biases towards cigarettes Background Although experts cl aim that computer-tailored interventions provided over the Internet have great potential to promote health behavior change , few studies have tested the efficacy of computer-tailored lifestyle interventions online-delivered over the Internet . Purpose To evaluate the short-term ( 1 month ) efficacy of an Internet-delivered , computer-tailored lifestyle intervention targeting saturated fat intake , physical activity ( PA ) , and smoking cessation , and to evaluate exposure to the intervention . Methods A pretest – posttest r and omized controlled trial with an intervention group and a no intervention waiting list control group was conducted . Self-reported behavior and determinants were assessed at baseline and 1 month follow-up . Exposure to the intervention was monitored through server registration s. The data were analyzed using multiple linear and logistic regression analysis . Results The intervention result ed in a significantly lower self-reported saturated fat intake ( b = −0.76 , p < 0.01 ) and a higher likelihood of meeting the PA guidelines among respondents who were insufficiently active at baseline ( OR = 1.34 , 95%CI = 1.001–1.80 ) . No significant intervention effects were found for self-reported smoking status . Of the participants , 81 % actually visited the website . Conclusions The Internet-delivered , computer-tailored lifestyle intervention was effective in reducing self-reported saturated fat intake and in increasing self-reported PA among participants who completed the study To determine the influence of exercise training on smoking after acute myocardial infa rct ion ( AMI ) , smoking rates in 42 pre-AMI smokers assigned to exercise training were compared with 26 pre-AMI smokers assigned to no training . Exercise training occurred 3 - 26 weeks after AMI . The increase in functional capacity in 3 - 26 weeks was significantly greater in training than in no-training patients : 1.8 vs. 1.2 METs respectively ( p less than 0.05 ) . Adherence to exercise training was higher in non-smokers and former smokers than in those who continued to smoke : 89 % and 88 % vs. 80 % respectively ( NS ) . The prevalence of smoking 6 months post-AMI was lower in training than in no-training patients : 31 % vs. 39 % respectively ( NS ) . Plasma thiocyanates collected on a r and om sample of 42 patients suggested that 19 % of patients who are smoking after MI fail to report doing so . Self-reported cigarette consumption at 28 weeks was half as great in training as in no-training patients : 11 + /- 7 vs. 22 + /- 16 cigarettes per day ( p less than 0.03 ) . Firm advice to stop smoking followed by medically supervised exercise training with frequent followup reduces self-reported cigarette consumption in patients after AMI AIM To examine whether exercise counselling increases smoking abstinence and reduces tobacco withdrawal and gains in weight and body fat . DESIGN A r and omized controlled trial . SETTING A community-based stop smoking clinic . PARTICIPANTS Two hundred and ninety-nine male and female smokers . INTERVENTION Participants were assigned r and omly to a 7-week smoking cessation programme , including nicotine replacement therapy plus either ( i ) exercise counselling , or ( ii ) health education advice with equal contact time as for the exercise counselling condition . MEASUREMENTS Six weeks of smoking abstinence was confirmed by expired carbon monoxide . FINDINGS There was no significant difference in smoking abstinence between the exercise group ( n = 154 ) and the controls ( n = 145 ) at 6 weeks ( 39.6 % versus 38.6 % ) , nor was there any difference in gains in weight or body fat , although those in the exercise group increased their exercise levels . Exercise participants reported less tension , anxiety and stress than the controls during the first week of smoking abstinence ( P = 0.03 , 0.01 and 0.04 , respectively ) , less irritability throughout 2 weeks of abstinence ( P = 0.03 ) , and less restlessness throughout 3 weeks of abstinence ( P = 0.04 ) . CONCLUSIONS Adding brief exercise counselling to a smoking cessation programme did not increase smoking abstinence or reduce gains in weight or body fat significantly , although exercise levels were raised and there were some beneficial effects on psychological symptoms Smoking cessation treatment is now integrated into many health-care systems and a major research effort is under way to improve current success rates . Until now results from r and omized clinical trials have been reported in many different ways , leading to problems of interpretation . We propose six st and ard criteria comprising the ' Russell St and ard ' ( RS ) . These criteria are applicable to trials of cessation aids where participants have a defined target quit date and there is face-to-face contact with research ers or clinic staff , as follows . ( 1 ) Follow-up for 6 months ( RS6 ) or 12 months ( RS12 ) from the target quit date or the end of a predefined ' grace period ' ; ( 2 ) self-report of smoking abstinence over the whole follow-up period allowing up to five cigarettes in total ; ( 3 ) biochemical verification of abstinence at least at the 6-month or 12-month follow-up point ; ( 4 ) use of an ' intention-to-treat ' approach in which data from all r and omized smokers are included in the analysis unless they have died or moved to an untraceable address ( participants who are included in the analysis are counted as smokers if their smoking status at the final follow-up can not be determined ) ; ( 5 ) following-up ' protocol violators ' and using their true smoking status in the analysis ; and ( 6 ) collecting follow-up data blind to smokers ' allocation to trial group . We believe that these criteria provide the best compromise between practicability and surrogacy for long-term cessation and will enable meaningful comparison between studies . There may be good reasons why other outcome criteria would also be reported , and studies that involve interventions with special groups or where there is no design ated target quit date or face to face contact would need to adapt these criteria accordingly OBJECTIVE Recent evidence suggests physical activity may be protective against smoking initiation and increased smoking among youth . The present study explored the effects of a teen smoking cessation intervention supplemented with a physical activity module on participants ' physical activity outcomes . A secondary aim examined the relationship between participants ' physical activity outcomes and postprogram smoking intensity . DESIGN The study reports primary data from a 3-arm r and omized group trial consistent with CONSORT guidelines ( Registry # NCT01242657 ) . SETTING Public high schools ( N = 19 ) in West Virginia . PARTICIPANTS Teens aged 14 - 19 years ( N = 233 ) who reported current smoking , ≥1 cigarette in the past 30 days . INTERVENTION High schools were r and omly selected , then r and omly assigned to Brief Intervention ( st and ard of care ) , Not-On-Tobacco ( N-O-T , teen cessation program ) , or N-O-T plus a physical activity module ( N-O-T+FIT ) . OUTCOME MEASURES St and ardized instruments at baseline and end of treatment/3-months postbaseline measured physical activity outcomes . The study assessed smoking intensity using cigarettes smoked per day . We conducted ANCOVA controlling for school-level variance to measure physical activity changes . Multiple linear and logistic regression analyses explored favorable change influence of physical activity on smoking cessation outcomes , controlling for potential clustering . RESULTS Teens who increased the number of days on which they received at least 20 minutes of exercise were significantly more likely to reduce their daily cigarette use , with those in the N-O-T+FIT condition having the highest likelihood of reducing smoking . Teens in the N-O-T+FIT condition who increased the number of days on which they received at least 30 minutes of exercise were significantly more likely than those in other groups to quit smoking . CONCLUSION Findings suggest that it is possible to alter simultaneously more than one health behavior among teens-favorable changes in physical activity and smoking cessation may be particularly compatible targets for dual behavior change Although a high percentage of smokers attempt to quit each year , success rates are low . Thus , public health strategies must not only convince some smokers to attempt cessation , but also improve the success rate among other smokers already motivated to quit . Specific cessation strategies may be required for smokers in these two groups . This study compares sociodemographic and health behavior characteristics of smokers who have and have not attempted to quit and of those who recently succeeded . To determine whether these characteristics vary for men and women , we stratified analyses on gender . Data were obtained from r and om sample health surveys conducted 1981 - 1982 and 1983 - 1984 in two New Engl and communities . Analyses include data on 2,086 respondents who reported smoking cigarettes in the previous year . Men and women were equally likely both to attempt cessation and to quit . Except for an inverse association with age , attempting to quit was not associated with sociodemographic variables . In men and women , attempts were associated with encouraging others to quit and attempting to increase exercise . Successful cessation attempts were associated with not living with a smoker in women ; marital status , attempted weight loss , and increased age in men ; and with efforts to increase exercise in both men and women . These characteristics could be useful in targeting smokers who attempt to quit , but fail . Improving the success rate in this group could greatly reduce smoking prevalence in the community UNLABELLED Cigarette smoking is the leading preventable cause of death and disease among adults , and there is evidence that smokers with multiple sclerosis ( MS ) are at an increased risk for accelerated disease conversion and progression toward disability . Recent research has shown resistance training ( i.e. , weight training ) to be beneficial for smoking cessation in the general population ; however , no study has examined the use of resistance training as an aid to cessation in those with MS . METHODS After receiving brief smoking cessation counseling and the nicotine patch , smokers with relapsing-remitting MS will be r and omized into a Resistance Training ( RT ) or Contact Control ( CC ) group . Participants in the RT group will attend a 60-minute resistance training session twice weekly for eight weeks , while participants in the CC will attend a 30-minute health education control session twice weekly for eight weeks . Measurements will be taken at baseline , weekly during the intervention , at the end of the eight-week study period , and at a one-month follow-up . The primary outcome will be smoking cessation , indicated by a 7-day abstinence , and verified by biochemical assay ( i.e. , carbon monoxide breath test ) . Secondary outcomes will include other smoking-related variables ( e.g. , nicotine withdrawal symptoms ) , multiple sclerosis-related factors ( e.g. , fatigue ) , and physical assessment s ( e.g. , muscular strength ) . DISCUSSION The results from this study will lay the foundation for subsequent tests of the intervention in smokers with MS , with the long-term goal of providing specific recommendations and guidelines for smoking cessation that can be integrated into the clinical care of persons with MS The authors compared simultaneous versus sequential approaches to multiple health behavior change in diet , exercise , and cigarette smoking . Female regular smokers ( N = 315 ) r and omized to 3 conditions received 16 weeks of behavioral smoking treatment , quit smoking at Week 5 , and were followed for 9 months after quit date . Weight management was omitted for control and was added to the 1st 8 weeks for early diet ( ED ) and the final 8 weeks for late diet ( LD ) . ED lacked lasting effect on weight gain , whereas LD initially lacked but gradually acquired a weight-suppression effect that stabilized ( p = .004 ) . Behavioral weight control did not undermine smoking cessation and , when initiated after the smoking quit date , slowed the rate of weight gain , supporting a sequential approach This prospect i ve study examined the effect of three behavioral smoking interventions and reductions in cigarettes smoked per day on nicotine withdrawal symptoms in 141 abstinent alcoholic smokers ( 73 men , 68 women ) . The participants ' mean + /- SD age was 41.4 + /- 9.2 years . They smoked an average of 27.7 + /- 12.1 cigarettes per day and reported 4.1 + /- 4.3 years of current abstinent from alcohol and other drugs of dependence . Participants were r and omly assigned to a 12-week program of st and ard treatment ( ST , n = 61 ) , behavioral counseling plus exercise ( BEX , n = 39 ) , or behavioral counseling plus nicotine gum ( BNIC , n = 41 ) . All three conditions included instructions to reduce the number of cigarettes smoked per day prior to the target quit date ( TQD ) . The TQD was week 4 for ST subjects and week 8 for those in the BEX and BNIC groups . The post-treatment assessment occurred one week after TQD . The Profile of Mood States ( POMS ) and the Beck Depression Inventory were administered at baseline and posttreatment to assess nicotine withdrawal . Significant increases were detected for the POMS total mood disturbance score , and the depression , tension , anger and confusion subscales , while vigor scores decreased ( all p < 0.03 ) . Withdrawal change scores were not found to be associated with treatment condition or percentage reduction in cigarettes , and there was no evidence of a significant interaction of treatment and cigarette reduction . Results are discussed in relation to implication s for treatment and for future research Background Tobacco smoking remains the leading preventable cause of death among American women . Exercise has shown promise as an aid to smoking cessation because it reduces weight gain and weight concerns , improves affect , and reduces nicotine withdrawal symptoms and cigarette craving . Studies have shown that the practice of yoga improves weight control , and reduces perceived stress and negative affect . Yoga practice also includes regulation of breathing and focused attention , both of which may enhance stress reduction and improve mood and well-being and may improve cessation outcomes . Methods / Design This pilot efficacy study is design ed to examine the rates of cessation among women r and omized to either a novel , 8-week Yoga plus Cognitive Behavioral Therapy ( CBT ) smoking cessation intervention versus a Wellness program plus the same CBT smoking cessation intervention . Outcome measures include 7-day point prevalence abstinence at end of treatment , 3 and 6 months follow up and potential mediating variables ( e.g. , confidence in quitting smoking , self-efficacy ) . Other assessment s include measures of mindfulness , spirituality , depressive symptoms , anxiety and perceived health ( SF-36 ) . Discussion Innovative treatments are needed that address barriers to successful smoking cessation among men and women . The design chosen for this study will allow us to explore potential mediators of intervention efficacy so that we may better underst and the mechanism(s ) by which yoga may act as an effective complementary treatment for smoking cessation . If shown to be effective , yoga can offer an alternative to traditional exercise for reducing negative symptoms that often accompany smoking cessation and predict relapse to smoking among recent quitters . Trial Registration Clinical Trials Background Health promotion is a key component for primary prevention of cardiovascular disease ( CVD ) . This study evaluated the impact of healthy lifestyle promotion campaigns on CVD risk factors ( CVDRF ) in the general population in the context of a community-based programme on hypertension management . Methods A quasi-experimental intervention study was carried out in two rural communes of Vietnam from 2006 to 2009 . In the intervention commune , a hypertensive-targeted management programme integrated with a community-targeted health promotion was initiated , while no new programme , apart from conventional healthcare services , was provided in the reference commune . Health promotion campaigns focused on smoking cessation , reducing alcohol consumption , encouraging physical activity and reducing salty diets . Repeated cross-sectional surveys in local adult population aged 25 years and over were undertaken to assess changes in blood pressure ( BP ) and behavioural CVDRFs ( smoking , alcohol consumption , physical inactivity and salty diet ) in both communes before and after the 3-year intervention . Results Overall 4,650 adults above 25 years old were surveyed , in four r and omly independent sample s covering both communes at baseline and after the 3-year intervention . Although physical inactivity and obesity increased over time in the intervention commune , there was a significant reduction in systolic and diastolic BP ( 3.3 and 4.7 mmHg in women versus 3.0 and 4.6 mmHg in men respectively ) in the general population at the intervention commune . Health promotion reduced levels of salty diets but had insignificant impact on the prevalence of daily smoking or heavy alcohol consumption . Conclusion Community-targeted healthy lifestyle promotion can significantly improve some CVDRFs in the general population in a rural area over a relatively short time span . Limited effects on a context -bound CVDRF like smoking suggested that higher intensity of intervention , a supportive environment or a gender approach are required to maximize the effectiveness and maintain the sustainability of the health intervention BACKGROUND Commit to Quit II is a 4-year r and omized controlled trial comparing the efficacy of a cognitive-behavioral smoking cessation treatment plus moderate-intensity physical activity with the same cessation treatment plus contact control . METHODS Sedentary women smokers ( n = 217 ) were r and omized to receive 8 weeks of treatment followed by 12 months of follow-up . This article outlines the study design , presents baseline data about the sample , and compares the sample to national sample s and to our previous study examining vigorous-intensity exercise as an aid to smoking cessation . RESULTS Married and white participants reported significantly higher levels of nicotine dependence than unmarried and minority participants . Higher levels of nicotine dependence were also significantly related to lower smoking cessation self-efficacy and higher levels of self-reported depression , anxiety , and perceived stress . Additionally , participants smoked significantly more cigarettes ( mean 20.6 ) than a national sample of female smokers ( mean 16.1 ) . On average , participants were significantly older , weighed significantly more , and scored significantly higher on a measure of anxiety than participants in our previous trial . CONCLUSIONS Our sample consisted of women who were heavier smokers than national sample s seeking treatment . It remains to be determined how this will impact their ability to attain cessation in the present study OBJECTIVES The purpose of this study was to examine prospect ively whether exercise can modify weight gain after smoking cessation in women . METHODS Data were analyzed from a 2-year follow-up period ( 1986 - 1988 ) in the Nurses ' Health Study , an ongoing cohort of 121,700 US women aged 40 to 75 in 1986 . RESULTS The average weight gain over 2 years was 3.0 kg in the 1474 women who stopped smoking , and 0.6 kg among the 7832 women who continued smoking . Among women smoking 1 to 24 cigarettes per day , those who quit without changing their levels of exercise gained an average of 2.3 kg more ( 95 % confidence interval [ CI ] = 1.9 , 2.6 ) than women who continued smoking . Women who quit and increased exercise by between 8 to 16 MET-hours ( the work metabolic rate divided by the resting metabolic rate ) per week gained 1.8 kg ( 95 % CI = 1.0 , 2.5 ) , and the excess weight gain was only 1.3 kg ( 95 % CI = 0.7 , 1.9 ) in women who increased exercise by more than 16 MET-hours per week . CONCLUSIONS Smoking cessation is associated with a net excess weight gain of about 2.4 kg in middle-aged women . However , this weight gain is minimized if smoking cessation is accompanied by a moderate increase in the level of physical activity BACKGROUND Many patients in primary care setting s present with multiple behavioral risk factors for cardiovascular disease . Research has provided little information on the most effective ways to approach multiple behavior change counseling in clinical setting s. METHODS We implemented a r and omized trial in a publicly funded primary care setting to test whether a sequential presentation of stage of change-based counseling to stop smoking , reduce dietary sodium level to less than 100 mEq/L per day , and increase physical activity by at least 10,000 pedometer steps per week would be more effective than simultaneous counseling . African Americans with hypertension , aged 45 to 64 years , initially nonadherent to the 3 behavioral goals , were r and omized to the following conditions : ( 1 ) 1 in-clinic counseling session on all 3 behaviors every 6 months , supplemented by motivational interviewing by telephone for 18 months ; ( 2 ) a similar protocol that addressed a new behavior every 6 months ; or ( 3 ) 1-time referral to existing group classes ( " usual care " ) . The primary end point was the proportion in each arm that met at least 2 behavioral criteria after 18 months . RESULTS A total of 289 individuals ( 67.3 % female ) were r and omized , and 230 ( 79.6 % ) completed the study . At 18 months , only 6.5 % in the simultaneous arm , 5.2 % in the sequential arm , and 6.5 % in the usual-care arm met the primary end point . However , results for single behavioral goals consistently favored the simultaneous group . At 6 months , 29.6 % in the simultaneous , 16.5 % in the sequential , and 13.4 % in the usual-care arms had reached the urine sodium goal ( P = .01 ) . At 18 months , 20.3 % in the simultaneous , 16.9 % in the sequential , and 10.1 % in the usual-care arms were urine cotinine negative ( P = .08 ) . CONCLUSIONS Long-term multiple behavior change is difficult in primary care . This study provides strong evidence that addressing multiple behaviors sequentially is not superior to , and may be inferior to , a simultaneous approach In this pilot project , 41 female weight-concerned smokers were r and omly assigned to receive either 12 group sessions of cognitive behavioral therapy for body image concerns or 12 group sessions for weight management . All subjects received open-label bupropion SR , 300 mg daily , exercise instruction , and weekly behavioral counseling for tobacco cessation . At week 12 , 7(35 % ) of the body image participants had 7-day point prevalence smoking abstinence , compared to 5(24 % ) of the participants in the weight management group ( p=0.505 ) INTRODUCTION Research indicates that exercise may be helpful for smoking cessation ; however , the majority of studies have focused only on women and only on aerobic exercise . This pilot study explored the use of resistance training ( RT ) ( i.e. , weight lifting ) as an adjunctive strategy for quitting smoking for both men and women . METHODS A sample of 25 smokers received a brief smoking cessation counseling session and the nicotine patch prior to being r and omized into a 12-week RT or contact control ( CC ) group . Assessment s were conducted at baseline , 3-month , and at a 6-month follow-up . RESULTS Participants ( 52 % female ) averaged 36.5 years ( SD = 12.0 ) of age and 19.1 years ( SD = 12.0 ) of smoking . At the 3-month assessment , objective ly verified 7-day point prevalence abstinence ( PPA ) rates were 46 % for the RT group and 17 % for CC ; prolonged abstinence rates were 16 % and 8 % , respectively . At the 6-month assessment , objective ly verified 7-day PPA rates were 38 % for the RT group and 17 % for CC ; prolonged abstinence rates were 15 % and 8 % , respectively . Mean body weight decreased 0.6 kg ( SD = 1.7 ) in the RT group and increased 0.6 kg ( SD = 2.8 ) in the CC group . Mean body fat decreased 0.5 % ( SD = 1.8 ) in the RT group and increased 0.6 % ( SD = 0.7 ) in the CC . CONCLUSIONS This is the first study reporting on the use of a RT program as an aid to smoking cessation treatment . The findings suggest that such a program is feasible as an adjunctive treatment for smoking cessation . An adequately powered trial is warranted Background Smoking cessation remains a significant public health problem . Innovative interventions that use the Internet have begun to emerge that offer great promise in reaching large numbers of participants and encouraging widespread behavior change . To date , the relatively few controlled trials of Web-based smoking cessation programs have been limited by short follow-up intervals . Objective We describe the 6-month follow-up results of a r and omized controlled trial in which participants recruited online were r and omly assigned to either a Web-based smoking cessation program ( Quit Smoking Network ; QSN ) or a Web-based exercise enhancement program ( Active Lives ) adapted somewhat to encourage smoking cessation . Methods The study was a two-arm r and omized controlled trial that compared two Web-based smoking cessation programs : ( 1 ) the QSN intervention condition presented cognitive-behavioral strategies , and ( 2 ) the Active Lives control condition provided participants with guidance in developing a physical activity program to assist them with quitting . The QSN condition provided smoking cessation information and behavior change strategies while the Active Lives condition provided participants with physical activity recommendations and goal setting . The QSN condition was design ed to be more engaging ( eg , it included multimedia components ) and to present much greater content than is typically found in smoking cessation programs . Results Contrary to our hypotheses , no between-condition differences in smoking abstinence were found at 3- and 6-month follow-up assessment s. While participants in the QSN intervention condition spent more time than controls visiting the online program , the median number of 1.0 visit in each condition and the substantial attrition ( 60.8 % at the 6-month follow-up ) indicate that participants were not as engaged as we had expected . Conclusions Contrary to our hypothesis , our test of two Web-based smoking cessation conditions , an intervention and an attention placebo control , failed to show differences at 3- and 6-month assessment s. We explored possible reasons for this finding , including limited engagement of participants and simplifying program content and architecture . Future research needs to address methods to improve participant engagement in online smoking cessation programs . Possible approaches in this regard can include new informed consent procedures that better explain the roles and responsibilities of being a research participant , new program design s that add more vitality ( changing content from visit to visit ) , and new types of reminders pushed out to participants to encourage return visits . Simplifying program content through a combination of enhanced tailoring and information architecture also merits further research attention The urges to smoke reported by 215 former smokers were measured 1 day , 7 days , 14 days and 30 days after they quit to examine : ( a ) the time course of smoking urges , ( b ) the relationship of urges to relapse , and ( c ) predictors of urges to smoke . Urges to smoke were strongest 1 day after quitting , and decreased at each subsequent measurement point . Urges were a powerful predictor of relapse . At each of the four assessment points , abstinent subjects who reported stronger urges to smoke were more likely to relapse by the next measurement point . Urges to smoke at a given day ( e.g. , day 1 ) were consistently the best predictors of the persistence of urges at the next assessment ( e.g. , day 7 ) . Greater negative emotion ( e.g. , anxiety , sadness , anger , and confusion ) and psychosocial stress also predicted stronger urges to smoke . Nicotine gum significantly reduced urges during week 1 post-cessation . Clinical implication s of the findings are discussed BACKGROUND : In adults it is recommended that the minimum of 10,000 steps/day should be performed in order to consider an individual as active . The pedometer , a small device that counts steps , has been used to monitor and /or motivate physical activity in various population s. OBJECTIVE : To investigate the short-term effects of a protocol using a pedometer or an informative booklet to increase daily physical activity in apparently healthy smokers who reached or did not reach the minimum public health recommendation of 10,000 steps/day . METHODS : Subjects were r and omly assigned to 2 groups : group pedometer ( GP , n = 23 ) , who wore a pedometer every day during 1 month , aim ing to achieve 10,000 steps/day ; and group booklet ( GB , n = 17 ) , who received a booklet with encouragement to walk as much as possible in everyday life . Each group was subdivided according to their baseline daily physical activity level : active ( subjects who achieved 10,000 steps/day ) , and inactive ( those who did not achieve this minimum ) . RESULTS : Only the physically inactive GP increased significantly its daily physical activity ( pre vs post 7,670 [ 6,159–9,402 ] steps/day vs 10,310 [ 9,483–11,110 ] steps/day , P < .001 ) , with a concomitant increase in the 6-min walking test ( 6MWT ) distance ( mean and interquartile range 540 m [ 501–586 m ] vs 566 m [ 525–604 m ] , P = .03 ) . In GP , Δ post-pre steps/day correlated significantly with baseline number of steps/day ( r = −0.63 , P = .01 ) , but not with 6MWT . In the inactive subjects ( summing GP and GB ) , there were significant correlations between steps/day and cigarettes/day , pack-years , and Fagerström question naire ( r = −0.55 , −0.40 , and −0.59 , P ≤ .05 for all ) . Furthermore , improvement in steps/day in the inactive subjects of GP was correlated with baseline cigarettes smoked per day , pack-years , and Fagerström question naire ( r = 0.51 , 0.65 and 0.53 , P ≤ .05 for all ) . CONCLUSIONS : Physically inactive smokers improve their daily physical activity level by using a simple tool ( pedometer ) , and larger improvement occurs in subjects with the lowest levels of physical activity Background We examined female sedentary smokers ' additional cardiovascular disease ( CVD ) risk behaviors and their associations to smoking cessation . Methods This study was part of a r and omized controlled trial testing the effectiveness of exercise and nicotine gum in smoking cessation . Included in the analyses were 148 participants . Dietary habits and alcohol consumption were measured as additional CVD risk behaviors . High-fat diet and heavy alcohol use were considered those risk behaviors . Nicotine dependence , length of the longest quit attempt , depressive symptoms , self-efficacy , and education were examined as other baseline variables . Abstinence from tobacco was recorded through 12 months . Results Diet was related to depressive symptoms at baseline . Alcohol use was related to nicotine dependence and education level . Heavy alcohol use alone and accumulation of two added risk behaviors predicted poorer smoking cessation outcome . Although diet alone was not associated with cessation outcome the high-fat diet interacted with depressive symptoms , such that the depressed women with high-fat diet were significantly more likely to relapse in their quit attempt compared to other subgroups . Conclusion Non-moderate alcohol use alone and accumulation of multiple CVD risk behaviors seem to be associated with lower success in smoking cessation Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE : To underst and the influence of physical activity on teen smoking-cessation outcomes . METHODS : Teens ( N = 233 ; 14–19 years of age ) from West Virginia high schools who smoked > 1 cigarette in the previous 30 days were included . High schools with > 300 students were selected r and omly and assigned to brief intervention ( BI ) , Not on Tobacco ( N-O-T ) ( a proven teen cessation program ) , or N-O-T plus a physical activity module ( N-O-T+FIT ) . Quit rates were determined 3 and 6 months after baseline by using self-classified and 7-day point prevalence quit rates , and carbon monoxide validation was obtained at the 3-month follow-up evaluation . RESULTS : Trends for observed and imputed self-classified and 7-day point prevalence rates indicated that teens in the N-O-T+FIT group had significantly higher cessation rates compared with those in the N-O-T and BI groups . Effect sizes were large . Overall , girls quit more successfully with N-O-T compared with BI ( relative risk [ RR ] : > ∞ ) 3 months after baseline , and boys responded better to N-O-T+FIT than to BI ( RR : 2–3 ) or to N-O-T ( RR : 1–2 ) . Youths in the N-O-T+FIT group , compared with those in the N-O-T group , had greater likelihood of cessation ( RR : 1.48 ) at 6 months . The control group included an unusually large proportion of participants in the precontemplation stage at enrollment , but there were no significant differences in outcomes between BI and N-O-T ( z = 0.94 ; P = .17 ) or N-O-T+FIT ( z = 1.12 ; P = .13 ) participants in the precontemplation stage . CONCLUSIONS : Adding physical activity to N-O-T may enhance cessation success , particularly among boys Rationale Substances of misuse ( such as nicotine ) are associated with increases in activation within the mesocorticolimbic brain system , a system thought to mediate the rewarding effects of drugs of abuse . Pharmacological treatments have been design ed to reduce cigarette cravings during temporary abstinence . Exercise has been found to be an effective tool for controlling cigarette cravings . Objective The objective of this study is to assess the effect of exercise on regional brain activation in response to smoking-related images during temporary nicotine abstinence . Method In a r and omized crossover design , regular smokers ( n = 10 ) undertook an exercise ( 10 min moderate-intensity stationary cycling ) and control ( passive seating for same duration ) session , following 15 h of nicotine abstinence . Following treatments , participants entered a functional Magnetic Resonance Imaging ( fMRI ) scanner . Subjects viewed a r and om series of smoking and neutral images for 3 s , with an average inter-stimulus-interval ( ISI ) of 10 s. Self-reported cravings were assessed at baseline , mid- , and post-treatments . Results A significant interaction effect ( time by group ) was found , with self-reported cravings lower during and following exercise . During control scanning , significant activation was recorded in areas associated with reward ( cau date nucleus ) , motivation ( orbitofrontal cortex ) and visuo-spatial attention ( parietal lobe , parahippocampal , and fusiform gyrus ) . Post-exercise scanning showed hypo-activation in these areas with a concomitant shift of activation towards areas identified in the ‘ brain default mode ’ ( Broadmanns Area 10 ) . Conclusion The study confirms previous evidence that a single session of exercise can reduce cigarette cravings , and for the first time provides evidence of a shift in regional activation in response to smoking cues Background Although cigarette smoking is a leading cause of death and disability in the United States ( US ) , over 40 million adults in the US currently smoke . Quitting smoking is particularly difficult for smokers with certain types of psychological vulnerability . Research ers have frequently called attention to the relation between smoking and anxiety-related states and disorders , and evidence suggests that panic and related anxiety vulnerability factors , specifically anxiety sensitivity ( AS or fear of somatic arousal ) , negatively impact cessation . Accordingly , there is merit to targeting AS among smokers to improve cessation outcome . Aerobic exercise has emerged as a promising aid for smoking cessation for this high-risk ( for relapse ) group because exercise can effectively reduce AS and other factors predicting smoking relapse ( for example , withdrawal , depressed mood , anxiety ) , and it has shown initial efficacy for smoking cessation . The current manuscript presents the rationale , study design and procedures , and design considerations of the Smoking Termination Enhancement Project ( STEP ) . Methods STEP is a r and omized clinical trial that compares a vigorous-intensity exercise intervention to a health and wellness education intervention as an aid for smoking cessation in adults with elevated AS . One hundred and fifty eligible participants will receive st and ard treatment ( ST ) for smoking cessation that includes cognitive behavioral therapy ( CBT ) and nicotine replacement therapy ( NRT ) . In addition , participants will be r and omly assigned to either an exercise intervention ( ST+EX ) or a health and wellness education intervention ( ST+CTRL ) . Participants in both arms will meet 3 times a week for 15 weeks , receiving CBT once a week for the first 7 weeks , and 3 supervised exercise or health and wellness education sessions ( depending on r and omization ) per week for the full 15-week intervention . Participants will be asked to set a quit date for 6 weeks after the baseline visit , and smoking cessation outcomes as well as putative mediator variables will be measured up to 6 months following the quit date . Discussion The primary objective of STEP is to evaluate whether vigorous-intensity exercise can aid smoking cessation in anxiety vulnerable adults . If effective , the use of vigorous-intensity exercise as a component of smoking cessation interventions would have a significant public health impact . Specifically , in addition to improving smoking cessation treatment outcome , exercise is expected to offer benefits to overall health , which may be particularly important for smokers . The study is also design ed to test putative mediators of the intervention effects and therefore has the potential to advance the underst and ing of exercise-anxiety-smoking relations and guide future research on this topic . Clinical trials registry Clinical Trials.gov , NCT01065506 , http:// clinical This study examined baseline predictors associated with smoking abstinence among 205 smokers ( 113 men , 92 women ) with a past history of alcoholism . Their mean age was 41.8 years , and 93 % were Caucasian . Participants were r and omly assigned to st and ard treatment ( ST ) , behavioral counseling plus exercise ( BEX ) , or behavioral counseling plus nicotine gum ( BNIC ) . Factors multivariately associated with point-prevalence smoking abstinence at posttreatment ( 1 week after target quit date ) were a longer duration of prior smoking abstinence and an interaction between treatment group and having an active 12-step sponsor . ST was more effective for those with an active sponsor , whereas both BEX and BNIC were more effective for those without an active sponsor . At 1-year follow-up , independent predictors of point-prevalence smoking abstinence were a lower Fagerström Tolerance Question naire score ( K. O. Fagerström , 1978 ) and fewer years of smoking The present study was conducted to examine the effects of acute aerobic exercise on smoking behavior . On alternate days , 10 healthy young smokers were subjected to half an hour of sustained high exercise ( about 56 % of maximum work capacity ) or of low exercise ( about 28 % of maximum , simulating normal daytime activity ) . During the high-exercise condition , there were pronounced increases in physiological markers of physical activity such as mean work , heart rate , and lactic acid as well as elevations in circulating hormones ( norepinephrine , epinephrine , and immunoreactive beta-endorphin and cortisol ) known to be affected by vigorous exercise . Despite a trend toward decreased desire for cigarettes after the high exercise condition , there were no differences in plasma nicotine levels following the smoking of a usual-br and cigarette 35 min later . The sustained effects of the two exercise conditions were also similar : plasma cotinine levels 24 hr later ( reflecting nicotine intake over the entire exercise day ) revealed no significant differences between hight and low exercise PURPOSE To examine the individual effects of supervised and intensive exercise as well as the combined effects of exercise and nicotine replacement therapy ( NRT ) on ( a ) smoking cessation and reduction rates and ( b ) psychological and physiological processes during withdrawal . METHODS One-hundred and forty-two inactive female smokers were r and omised into the following four groups : exercise+nicotine patch ; exercise+no nicotine patch ; cognitive behavior therapy (CBT)+nicotine patch and CBT+no nicotine patch . Smoking abstinence ( verified by saliva cotinine and expired carbon monoxide ) , cessation self-efficacy , and physical fitness and body weight were assessed at baseline ( week 1 ) , quit date ( week 6 ) , program termination ( week 12 ) , and 3- and 12-month follow-up . RESULTS There were significant differences in a 7-day point prevalence but not continuous abstinence rates between treatment groups across targeted end points . Consistently higher cessation rates were seen when NRT was added to both treatment programs . Compared with CBT participants , exercise participants had significantly increased functional exercise capacity and had gained significantly less weight during program end points but these differences did not hold at a 12-month follow-up . Compared with exercise participants , CBT participants felt greater cessation efficacy and reported greater knowledge , coping and support re sources across all end points . CONCLUSIONS Exercise combined with NRT facilitates smoking cessation , improves functional exercise capacity , and delays weight gain in women smokers . We recommend that physicians and health care professionals recommend exercise and NRT together for highly motivated women interested in quitting smoking BACKGROUND Cigarette smokers with elevated blood pressure ( BP ) are at substantially higher risk for cardiovascular events compared to normotensive smokers . Although smoking cessation should be a primary treatment goal for these patients , increases in body weight accompanying smoking abstinence may further increase BP . Intervention strategies that facilitate smoking cessation and modify adverse changes in body weight and BP are needed . METHODS We describe an ongoing multi-site , two-phase , five-year r and omized clinical trial . Participants are cigarette smokers with Prehypertension or Stage I Hypertension . In the first phase , participants receive a smoking cessation intervention combining behavioral counseling and nicotine replacement in an open-label fashion . In the second phase , participants who successfully quit smoking are r and omly assigned to one of three lifestyle interventions : 1 ) weight gain prevention , 2 ) blood pressure control , or 3 ) usual lifestyle . Participants are followed for one year to assess changes in blood pressure , body weight , dietary intake , and physical activity . CONCLUSIONS Results from the proposed study will provide important insights into the efficacy of various approaches to lifestyle modification in smokers at increased risk for cardiovascular events AIM To examine the association between weight change and baseline body mass index ( BMI ) over 8 years in a cohort of continuing and quitting smokers . DESIGN Prospect i ve cohort . SETTING Oxfordshire general practice s nicotine patch/placebo trial with 8-year follow-up . PARTICIPANTS Eighty-five participants were biochemically proven abstinent at 3 , 6 , 12 months and 8 years ( abstainers ) . A total of 613 smoked throughout the 8 years ( smokers ) , 26 quit for a whole year but were smoking again by 8 years ( relapsed ) ; 116 smoked for the first year but were abstinent at 8 years ( late abstainers ) . MEASUREMENTS Weight and BMI was measured at baseline and at 8 years . Regression models were used to examine weight gain by smoking status and the association of BMI at the time of quitting . FINDINGS Abstainers gained 8.79 kg [ st and ard deviation ( SD ) 6.36 ; 95 % confidence interval ( CI ) 7.42 , 10.17 ] . Smokers gained 2.24 kg ( SD 6.65 ; 95 % CI 1.7 , 2.77 ) . Relapsed smokers gained 3.28 kg ( SD 7.16 ; 95 % CI 0.328 , 6.24 ) . Late abstainers gained 8.33 kg ( SD 8.04 ; 95 % CI 6.85 , 9.81 ) . The association between baseline BMI and weight change was modified by smoking status . In smokers there was a negative linear association of BMI , while in abstainers a J-shaped curve fitted best . These models estimated weight change over 8 years in abstainers of + 9.8 kg , + 7.8 kg , + 10.2 kg , + 19.4 kg and in smokers of + 3.9 kg , + 2.6 kg , 1.0 kg and -0.8 kg , where BMI was 18 , 23 , 29 and 36 , respectively . CONCLUSION Obese smokers gain most weight on quitting smoking , while obese continuing smokers are likely to remain stable or lose weight . Obese quitters have the greatest need for interventions to ameliorate weight gain Smoking cessation is possible for individuals with schizophrenia but the relapse rate is high . It is necessary to develop more flexible approaches to help these patients . The aim of this study was to examine the feasibility of an intervention approach that integrates counseling and exercise for participants with schizophrenia or schizoaffective disorder . A single group prospect i ve design was used in this study . A sample of in patients with schizophrenia or schizoaffective disorder participated in a program called " oxygen group " , a program combining five sessions of smoking reduction counseling and three sessions of moderate intensity exercise over an 8-week period . Tobacco consumption , motivation , carbon monoxide level , anxiety and depression , smoking self-efficacy , nicotine dependence and waist circumference were measured pre- and post-intervention . Participants reported their satisfaction with the study characteristics after completion of the intervention . Smoking consumption and CO level were assessed at 6-week post-intervention follow-up . Twelve individuals ( mean age 45.7±10.8years ) were recruited . Participant attendance was 81.3 % . There were no dropouts . Significant decreases were found for tobacco consumption ( P=.04 ) and CO rate ( P=.003 ) at the end of the intervention and were maintained at 6-week follow-up . Compared to baseline levels , there were no changes in depression and anxiety . Smoking cessation motivation increased significantly . This intervention appears feasible and acceptable to patients with schizophrenia and there were promising findings regarding smoking reduction . Larger trials to test the intervention are warranted PURPOSE This study investigated the combined effects of exercise and smoking cessation on serum lipids . METHODS Eighteen female smokers quit smoking using st and ard behavioral methods combined with exercise ( N = 9 ) or with a nonexercise contact time control ( N = 9 ) . The smoking cessation program for both groups consisted of 12 weekly 1-h behavioral modification sessions held over 12 wk . Exercise training consisted of three supervised 45-min sessions per week for 12 wk . Contact control consisted of three health education lectures/ discussion s per week for 12 wk . Fitness ( estimated VO2 peak ) , dietary variables , and fasting serum lipids and lipoproteins were assessed before and at the end of treatment . VO2 peak increased in the exercise subjects compared with the controls . RESULTS Total caloric intake as well as total fat and carbohydrate increased significantly after smoking cessation in the controls , but there were no dietary changes in the exercise group . high density lipoprotein (HDL)-C2 increased ( 7.6 mg x dL(-1 ) , P < 0.01 ) in the exercise group , whereas the increases in HDL and its subfractions did not attain statistical significance in the contact control group . Total cholesterol , low density lipoprotein (LDL)-C , and triglycerides did not change in either group . CONCLUSIONS We conclude that exercise training magnifies the increase in HDL-C that usually occurs with smoking cessation Background The organized Cervical Cancer Screening Programme ( CCSP ) in Italy might represent an occasion to deliver smoking cessation ( SC ) counselling to women attending the Pap test examination . Evidence of effectiveness of physical activity ( PA ) promotion and intervention in adjunct to SC counselling is not strong . Objective of the SPRINT trial was to evaluate the effectiveness of a st and ard SC counselling intervention delivered by trained midwives in the CCSP , and whether the adjunct of a PA counselling to the SC counselling might increase quit rates . Methods / Design We undertook a r and omized controlled trial of 1,100 women undergoing the Pap examination in the three study centres Florence , Turin , and Mantua : 363 were r and omly assigned to the SC counselling arm , 366 to the SC + PA counselling arm , and 371 to the control group . The intervention was a st and ard brief SC counselling combined with a brief counselling on increasing PA , and was tailored according to the Di Clemente-Prochaska motivational stages of change for SC and /or PA . Primary outcomes were quit rates , improvement in the motivational stages of change for SC , and reduced daily cigarette consumption . Analysis was by intention to treat . Results Participants r and omized in both intervention arms and in the preparation stage of change for SC doubled their likelihood of quitting at 6-month follow-up in comparison to controls ( odds ratio [OR]=2.1 , 95 % confidence interval [ 95 % CI]:1.0 - 4.6 ) . Moreover , participants in the intervention arms and in the contemplation stage were more likely to reduce their daily cigarette consumption after the intervention ( OR=1.8 , 95 % CI:1.1 - 3.0 ) . Our study did not show any effect of PA counselling on various outcomes . Conclusions Smoking cessation counselling delivered by midwives to smokers in preparation and contemplation stages of change during the Pap-smear screening was effective and should be recommended , given the high number of women attending the cervical cancer screening programme in Italy . Moreover , the daily number of women invited for the Pap-smear examination should be slightly lowered , in order to let midwives deliver SC counselling to smokers . Trial registration Current Controlled Trials IS RCT Background Interventions are needed which can successfully modify more than one disease risk factor at a time , but much remains to be learned about the acceptability , feasibility , and effectiveness of multiple risk factor ( MRF ) interventions . To address these issues and inform future intervention development , we conducted a r and omized pilot trial ( n = 52 ) . This study was design ed to assess the feasibility and acceptability of the Step Up program , a MRF cognitive-behavioral program design ed to improve participants ' mental and physical well-being by reducing depressive symptoms , promoting smoking cessation , and increasing physical activity . Methods Participants were recruited from a large health care organization and r and omized to receive usual care treatment for depression , smoking , and physical activity promotion or the phone-based Step Up counseling program plus usual care . Participants were assessed at baseline , three and six months . Results The intervention was acceptable to participants and feasible to offer within a healthcare system . The pilot also offered important insights into the optimal design of a MRF program . While not powered to detect clinical ly significant outcomes , changes in target behaviors indicated positive trends at six month follow-up and statistically significant improvement was also observed for depression . Significantly more experimental participants reported a clinical ly significant improvement ( 50 % reduction ) in their baseline depression score at four months ( 54 % vs. 26 % , OR = 3.35 , 95 % CI [ 1.01- 12.10 ] , p = 0.05 ) and 6 months ( 52 % vs. 13 % , OR = 7.27 , 95 % CI [ 1.85 - 37.30 ] , p = 0.004 ) Conclusions Overall , results suggest the Step Up program warrants additional research , although some program enhancements may be beneficial . Key lessons learned from this research are shared to promote the underst and ing of others working in this field . Trial registration The trial is registered with Clinical Trials.gov ( NCT00644995 ) Background Gender-specific smoking cessation strategies have rarely been developed . Evidence of effectiveness of physical activity ( PA ) promotion and intervention in adjunct to smoking cessation programs is not strong . SPRINT study is a r and omized controlled trial ( RCT ) design ed to evaluate a counselling intervention on smoking cessation and PA delivered to women attending the Italian National Health System Cervical Cancer Screening Program . This paper presents study design and baseline characteristics of the study population . Methods / Design Among women undergoing the Pap examination in three study centres ( Florence , Turin , Mantua ) , participants were r and omized to the smoking cessation counselling [ S ] , the smoking cessation + PA counselling [ S + PA ] , or the control [ C ] groups . The program under evaluation is a st and ard brief counselling on smoking cessation combined with a brief counselling on increasing PA , and was delivered in 2010 . A question naire , administered before , after 6 months and 1 year from the intervention , was used to track behavioural changes in tobacco use and PA , and to record cessation rates in participants . Discussion Out of the 5,657 women undergoing the Pap examination , 1,100 participants ( 55 % of smokers ) were r and omized in 1 of the 3 study groups ( 363 in the S , 366 in the S + PA and 371 in the C groups ) . The three arms did not differ on any demographic , PA , or tobacco-use characteristics . Recruited smokers were older , less educated than non-participant women , more motivated to quit ( 33 % vs.9 % in the Preparation stage , p < 0.001 ) , smoked more cigarettes per day ( 12 vs.9 , p < 0.001 ) , and were more likely to have already done 1 or more quit attempts ( 64 % vs.50 % , p < 0.001 ) . The approach of SPRINT study appeared suitable to enrol less educated women who usually smoke more and have more difficulties to quit . Trial registration numberIS RCT N : IS RCT INTRODUCTION Smoking during pregnancy is common , and quitting at any point during pregnancy can yield benefits to both the fetus and mother . Smoking cessation is typically followed by withdrawal symptoms and a strong desire to smoke , both of which are likely to contribute to relapse . Research has shown that a bout of exercise minimizes cravings and tobacco withdrawal symptoms ( TWS ) after temporary abstinence in smokers , but these findings have not been replicated in pregnant smokers . This study examined the effect of 20min of exercise on cravings ( primary outcome ) and TWS ( secondary outcomes ) among temporary abstinent , inactive pregnant smokers . METHODS Thirty female smokers ( Mean(M ) age=25.7years , St and ard Deviation(SD)=5.5 ; M weeks pregnant=18.2 , SD=5.3 ; Fagerstrom Test for Cigarette Dependence=3.3 , SD=2.2 ; M 9.3 cigarettes/day , SD=4.7 ; M hours abstained=17.2 , SD=2.8 ) were r and omized to 20 min of mild-to-moderate intensity exercise ( EC ; n=14 ) or passive ( PC ; n=16 ) condition . Cravings and TWS were assessed immediately before , during ( at 10 min ) , immediately post , and at 10 , 20 , and 30 min post-condition . RESULTS A 2 (condition) × 6 ( time ) repeated measures ANOVA revealed that the EC significantly ( p<0.05 ) reduced cravings ( ή(2)=0.46 ) compared with the PC , across time . Non-significant , but nevertheless , large effects were evident favouring the EC over time for TWS restlessness ( ή(2)=0.34 ) , stress ( ή(2)=0.24 ) , irritability ( ή(2)=0.21 ) , tension ( ή(2)=0.15 ) , and depression ( ή(2)=0.14 ) . CONCLUSIONS Consistent with previous research , this study reveals that in pregnant smokers , a bout of exercise is associated with a reduction in cravings and similar patterns exist for TWS . Therefore , exercise may have the potential to assist in the initial stages of smoking cessation attempts during pregnancy Purpose The aim of this study was to evaluate the effects of Vernonia cinerea Less . ( VC ) supplementation and exercise on oxidative stress biomarkers , beta-endorphin release , and the rate of cigarette smoking . Methods Volunteer smokers were r and omly divided into four groups : group 1 : VC supplement ; group 2 : exercise with VC supplement ; group 3 : exercise ; and group 4 : control . VC was prepared by wash and dry techniques and taken orally before smoking , matching the frequency of strenuous exercise ( three times weekly ) . Before and after a two month period , exhaled carbon monoxide ( CO ) , blood oxidative stress ( malondialdehyde [ MDA ] , nitric oxide [ NOx ] , protein hydroperoxide [ PrOOH ] and total antioxidant capacity [ TAC ] ) , beta-endorphin and smoking rate were measured , and statistically analyzed . Results In Group 1 , MDA , PrOOH , and NOx significantly decreased , whereas TAC increased ( p < 0.05 ) . In Group 2 , MDA and PrOOH decreased ( p < 0.05 ) , with no other changes noted ( p > 0.05 ) . In Group 3 , MDA , PrOOH , NOx , TAC , and beta-endorphin levels increased significantly ( p < 0.05 ) . Group 4 showed no change in oxidative stress variables or beta-endorphine levels ( p > 0.05 ) . All groups had lower levels of CO after the intervention . The smoking rate for light cigarette decreased in group 2(62.7 % ) , 1(59.52 % ) , 3 ( 53.57 % ) and 4(14.04 % ) , whereas in self-rolled cigarettes it decreased in group 1 ( 54.47 % ) , 3 ( 42.30 % ) , 2 ( 40 % ) and 4 ( 9.2 % ) . ConclusionS upplementation with Vernonia cinerea Less and exercise provided benefit related to reduced smoking rate , which may be related to oxidaive stress and beta-endorphine levels Background The main cause of relapse in smokers attempting to quit is inability to resist urges to smoke . Pharmacotherapy ameliorates but does not entirely prevent urges to smoke when abstinent , so other methods to resist urges to smoke might be helpful . Exercise is effective , but aerobic exercise is often impractical when urges strike . Two techniques , body scan and isometric exercise , have been shown to reduce urge intensity and nicotine withdrawal symptoms in temporarily abstinent smokers . It is unclear whether they would be used or effective in typical smokers attempting to quit . Methods In a pilot trial set in a UK smoking cessation clinic , 20 smokers were r and omised to receive emails containing .mp3 files and .pdf illustrations of the instructions for doing the body scan and isometric exercises . Twenty smokers received no other intervention , although all 40 were receiving weekly behavioural support and nicotine replacement therapy . Carbon monoxide confirmed abstinence , nicotine withdrawal symptoms , urges to smoke , and use of the techniques to resist urges were recorded weekly for four weeks after quit day . Results 60–80 % of quitters reported using the isometric exercises each week and 40–70 % reported using the body scan to deal with urges . On average , these techniques were rated as ' slightly helpful ' for controlling the urges . There were no large or significant differences in withdrawal symptoms or urge intensity between the two groups . The risk ratio and 95 % confidence interval for exercises compared with controls for prolonged confirmed abstinence at four weeks was 0.82 ( 0.44–1.53 ) . 81 % of quitters intended to continue using isometric exercises and 25 % body scan , while 81 % and 50 % respectively would recommend using these techniques to others trying to stop . Conclusion Isometric exercises , and to a lesser extent body scan , were popular and perceived as somewhat helpful by quitters . The trial showed that these techniques were used and a larger trial could now be developed to examine the influence of the methods on reducing urges to smoke and increasing abstinence . Trial registration IS RCT Rationale Smokers show heightened activation toward smoking-related stimuli and experience increased cravings which can precipitate smoking cessation relapse . Exercise can be effective for modulating cigarette cravings and attenuating reactivity to smoking cues , but the mechanism by which these effects occur remains uncertain . Objective The objective of the study was to assess the effect of exercise on regional brain activation in response to smoking-related images during temporary nicotine abstinence . Methods In a r and omised crossover design , overnight abstinent smokers ( n = 20 ) underwent an exercise ( 10-min moderate-intensity stationary cycling ) and passive control ( seating for the same duration ) treatment , following 15 h of nicotine abstinence . After each treatment , participants underwent functional magnetic resonance imaging ( fMRI ) brain scanning while viewing a r and om series of blocked smoking or neutral images . Self-reported cravings were assessed at baseline , mid- , and post-treatments . Results There was a significant interaction effect ( treatment × time ) for desire to smoke , F ( 2,32 ) = 12.5 , p < 0.001 , with significantly lower scores following the exercise at all time points compared with the control treatment . After both exercise and rest , significant areas of activation were found in areas of the limbic lobe and in areas associated with visual attention in response to smoking-related stimuli . Smokers showed increased activation to smoking images in areas associated with primary and secondary visual processing following rest , but not following a session of exercise . Conclusion The study shows differing activation towards smoking images following exercise compared to a control treatment and may point to a neuro-cognitive process following exercise that mediates effects on cigarette cravings Stress and exposure to smoking cues influence smoking cravings and behavior . Exercise appears to reduce cigarette cravings and withdrawal symptoms , but no study has investigated the effects of exercise on cue-elicited cravings and withdrawal symptoms , or ad libitum smoking behavior . In this study , 60 regular smokers , invited by public advertisements , were assessed at baseline following 2 hr of abstinence , and r and omized to a 15-min brisk walk or passive condition . Both groups then completed three tasks ( Stroop color-word interference task , speech task , and h and ling a lit cigarette ) . Cravings were assessed with two single items , and withdrawal symptoms were assessed using the seven-item Mood and Physical Symptoms Scale . After the laboratory session , ad libitum smoking was determined from the subject 's cell phone text message . Exercise ( mean heart rate reserve = 24 % ) attenuated increases in strength of desire to smoke , tension , poor concentration , and stress , in response to a lit cigarette , but had minimal effects on increases in cravings and withdrawal symptoms in response to the stressors . Absolute levels of cravings and withdrawal symptoms were reduced during and following exercise . Exercisers engaged in ad libitum smoking a net 57 min ( CI = 31 - 83 ) later than those in the passive condition . A 15-min brisk walk not only reduced cigarette cravings and withdrawal symptoms but also could attenuate increases in cue-elicited cravings and withdrawal symptoms , and increase the time between cigarettes smoked BACKGROUND Tobacco smoking remains the leading preventable cause of death among American women . Aerobic exercise has shown promise as an aid to smoking cessation because it improves affect and reduces nicotine withdrawal symptoms . Studies outside the realm of smoking cessation have shown that yoga practice also reduces perceived stress and negative affect . METHODS This pilot study examines the feasibility and initial efficacy of yoga as a complementary therapy for smoking cessation . Fifty-five women were given 8-week group-based cognitive behavioral therapy for smoking cessation and were r and omized to a twice-weekly program of Vinyasa yoga or a general health and wellness program ( contact control ) . The primary outcome measure was 7-day point prevalence abstinence at the end of treatment vali date d by saliva cotinine testing . Longitudinal analyses were also conducted to examine the effect of intervention on smoking cessation at 3- and 6-month follow-up . We examined the effects of the intervention on potential mediating variables ( e.g. , confidence in quitting smoking , self-efficacy ) , as well as measures of depressive symptoms , anxiety , and perceived health ( SF-36 ) . RESULTS At end of treatment , women in the yoga group had a greater 7-day point-prevalence abstinence rate than controls ( odds ratio [ OR ] , 4.56 ; 95 % CI , 1.1 - 18.6 ) . Abstinence remained higher among yoga participants through the six month assessment ( OR , 1.54 ; 95 % CI , 0.34 - 6.92 ) , although differences were no longer statistically significant . Women participating in the yoga program also showed reduced anxiety and improvements in perceived health and well-being when compared with controls . CONCLUSIONS Yoga may be an efficacious complementary therapy for smoking cessation among women Rationale Recent research has shown that 10 min of moderate intensity exercise reduce smoking withdrawal symptoms and desire to smoke in acutely abstinent smokers . The aim of the current study was to determine whether the reductions are related to participant expectation of these effects . Material s and methods Forty-five sedentary participants who had smoked ten or more cigarettes per day for at least 3 years reported their expectation of the effects of exercise on smoking withdrawal symptoms . Approximately 1 month later , participants were r and omly assigned to one of three groups after 11–15 h of overnight smoking abstinence . Each group read either a positive , negative or neutral statement concerning exercise effects on smoking withdrawal symptoms . They rated their expectation again and then completed 10 min of moderate intensity exercise on a stationary bicycle ergometer . Using st and ardised scales , participants rated smoking withdrawal symptoms and desire to smoke at 10 , 5 and 0 min before exercise , then at 5 and 10 min during exercise and 15 and 20 min post-exercise . Results Expectation of exercise effects on withdrawal were manipulated in the predicted directions . No significant group main effects were found for any symptom . Significant reductions in symptoms and desire to smoke occurred during and after exercise regardless of participant expectation . Conclusions Ten minutes of moderate intensity exercise can lead to reductions in desire to smoke and smoking withdrawal symptoms , which are not due to the participant ’s expectation of exercise effects . These findings support the use of short periods of exercise as an aid to smoking cessation Objectives Exercise combined with nicotine therapy may help smoking cessation and minimise weight gain after quitting . Low participation in vigorous-intensity physical activity programmes precludes their population -wide applicability . In a r and omised controlled trial , we tested whether a population -based moderate-intensity physical activity programme increases quit rates among sedentary smokers receiving nicotine therapy . Methods Participants ( n=481 ; 57 % male ; mean age , 42.2 years ( SD 10.1 ) ; mean cigarette consumption , 27 ( SD 10.2 ) per day ) were offered a nine-week smoking cessation programme consisting of a weekly 15-minute counselling session and the prescription of nicotine replacement therapy . In addition , participants in the physical activity group ( n=229 ) also took part in a programme of moderate-intensity physical activity implemented at the national level , and offering nine weekly 60-minute sessions of physical activity . To ensure equal contact conditions , participants in the control group ( n=252 ) attended weekly 60-minute health behaviour education sessions unrelated to physical activity . The primary outcome was continuous CO-verified smoking abstinence rates at 1-year follow-up . Results Continuous smoking abstinence rates were high and similar in the physical activity group and the control group at the end of the intervention ( 47 % versus 46 % , p=0.81 ) and at 1-year follow-up ( 27 % versus 29 % , p=0.71 ) . The mean weight gain after one year was 4.4 kg and 6.2 kg among sustained quitters of the physical activity and control groups , respectively ( p=0.06 ) . Conclusion Participation in a population -based moderate-intensity physical activity programme for 9 weeks in addition to a comprehensive smoking cessation programme did not significantly increase smoking cessation rates . A non-significant reduction in weight gain was observed among participants who quit smoking in the physical activity group . Trial registration Clinical Trials.gov ; US National Institutes for Health ( available online at http:// clinical trials.gov/ ; Clinical Trial Registration Number : NCT00521391 Smokers aged 18 to 65 years ( N = 1,044 ) who were able to quit for 24 hr were r and omized using a 2 x 2 factorial design to compare nicotine gum to no gum use and self-help material s to no use of material s. All participants were offered a $ 100 incentive to quit and stay quit for 6 months . Six-month abstinence was 27 % in the gum groups , compared with 19 % in the no-gum group ( p = .002 ) . Compared with the no-gum group , relapse occurred at a significantly lower rate in the gum group for the entire 12 months of follow-up ( odds of relapse in the gum group was 0.72 , 95 % confidence interval , 0.62 to 0.83 ) . There was no significant main effect for the self-help material s , no interaction between gum and material s , and no evidence that the effectiveness of gum differed between the sexes or between heavy and light smokers . Nicotine gum is an effective adjunct to minimal-contact smoking cessation material s plus monetary incentive in a population -based sample of smokers BACKGROUND Interventions using sustained aerobic exercise programs to aid smoking cessation have result ed in modest , short-term cessation rates comparable to conventional cessation methods . No smoking cessation trial to date has prescribed intermittent bouts of exercise in response to nicotine cravings . OBJECTIVES This pilot r and omized controlled trial examined the feasibility and efficacy of an Internet-based smoking cessation program alone ( CON ) vs. the same Internet-based program + intermittent exercise in response to cigarette cravings ( EX ) . STUDY POPULATION Participants ( N = 38 ; mean age = 43.6 [ SD = 11.5 ] ; 60.5 % women ) were generally healthy , inactive adult smokers who desired to quit . RESULTS The overall retention rate was 60.5 % ( n = 23 ) , and no significant retention rate differences were found between groups ( EX vs. CON ) . Although retained participants achieved a higher cessation rate ( 26.1 % ) than all enrolled participants ( 15.8 % ) , adjusted intent-to-treat and per- protocol binary logistic regression analyses revealed no significant cessation rate differences between EX and CON groups . Linear regression results indicated that additional days of self-reported exercise on the study website during the intervention phase predicted significantly higher reduction rates among EX group participants , F(2 , 16 ) = 31.08 , p < .001 . CONCLUSIONS Results were mixed with regard to the incremental benefit of exercise in the presence of the apparently valuable Internet-based smoking cessation program . The results support findings from related research and underscore the need for additional investigation into both the mechanisms underlying the effect of exercise on cigarette cravings and the challenges of poor adherence in the context of exercise-based smoking cessation interventions BACKGROUND Several cardiovascular disease ( CVD ) biomarkers sensitive to tobacco exposure have been identified , but how tobacco use cessation impacts them is less clear . We sought to investigate the effects of a smoking cessation program with an exercise intervention on CVD biomarkers in sedentary women . METHODS This is a cohort study on a sub sample of a 2 × 2 factorial r and omized controlled trial ( RCT ) ( exercise setting : home vs. facility ; level of exercise counseling : prescription only vs. prescription and adherence counseling ) conducted January 2004 through December 2007 . The analyses were completed in October 2010 . In the greater Boston area , 130 sedentary female smokers aged 19 - 55 completed a 15-week program . All participants received nicotine replacement therapy ( transdermal patch ) and brief behavioral counseling for 12 weeks . They all received an exercise prescription on a moderate intensity level . All exercise interventions lasted for 15 weeks , from 3 weeks precessation until 12 weeks postcessation . Main outcome measures were selected CVD biomarkers hypothesized to be affected by smoking cessation or exercise measured at baseline and 12 weeks postcessation . RESULTS Independent of tobacco abstinence , improvement was seen in inflammation ( white blood cells [ WBC ] ) , prothrombotic factor ( red blood cells [ RBC ] ) , and cardiovascular fitness level ( maximum oxygen consumption [ Vo(2)max ] ) . This suggests that even if complete abstinence is not achieved , reduction in tobacco exposure and increase in exercise can improve the cardiovascular risk profile . A significant decrease was seen for total cholesterol and the total cholesterol high-density lipoprotein cholesterol ( HDL-C ) : ratio only among the abstainers . The heart rate was reduced among all participants , but this decrease was more profound among abstainers . A significant weight gain and body mass index ( BMI ) increase were observed among abstainers and those who relapsed . We also found an increase in hemoglobin A1c ( Hb A1c ) , although significant only when the groups were combined . CONCLUSIONS A smoking cessation intervention including exercise reduced tobacco-induced cardiovascular damage selectively within 3 months A growing number of laboratory studies have shown that acute bouts of aerobic exercise favorably impact affect and cravings among smokers . However , r and omized trials have generally shown exercise to have no favorable effect on smoking cessation or withdrawal symptoms during quit attempts . The purpose of the present study was to explore this apparent contradiction by assessing acute changes in affect and cravings immediately prior to and following each exercise and contact control session during an eight-week smoking cessation trial . Sixty previously low-active , healthy , female smokers were r and omized to an eight-week program consisting of brief baseline smoking cessation counseling and the nicotine patch plus either three sessions/week of moderate intensity aerobic exercise or contact control . Findings revealed a favorable impact of exercise on acute changes in positive activated affect ( i.e. , energy ) , negative deactivated affect ( i.e. , tiredness ) , and cigarette cravings relative to contact control . However , effects dissipated from session to session . Results suggest that aerobic exercise has potential as a smoking cessation treatment , but that it must be engaged in frequently and consistently over time in order to derive benefits . Thus , it is not surprising that previous r and omized controlled trials-in which adherence to exercise programs has generally been poor-have been unsuccessful in showing effects of aerobic exercise on smoking cessation outcomes BACKGROUND Vigorous-intensity exercise has been shown to aid in smoking cessation , especially among women . In a previous trial , cognitive behavioral therapy ( CBT ) for smoking cessation plus regular vigorous aerobic exercise enhanced cessation rates , improved exercise capacity , and reduced weight gain compared to CBT plus equal contact time . PURPOSE This study examined the effectiveness of this program adapted for and implemented in the YMCAs . DESIGN An RCT comparing CBT + Exercise ( Exercise ) to CBT + Contact Control ( Control ) . SETTING / PARTICIPANTS Apparently healthy female smokers were recruited to four local YMCAs . INTERVENTION YMCA staff members were trained to lead the manualized CBT smoking-cessation intervention and a st and ardized YMCA exercise program . MAIN OUTCOME MEASURES Seven-day point prevalence and continuous abstinence . RESULTS Participants ( 330 women , mean age=44 years ) were r and omized to the Exercise ( n=166 ) or Control ( n=164 ) group . Results revealed no differences in 7-day point prevalence ( 29.5 % vs 29.9 % ) nor continuous abstinence ( 13.9 % vs 14.0 % ) between the Exercise and Control groups , respectively , at end of treatment or at the 3- , 6- , and 12-month follow-up . An examination of the relationship between exercise dose and quit status at end of treatment revealed that over 12 weeks , the odds of being quit ( 7-day point prevalence ) grew by 4.5 % for each additional aerobic exercise session ( OR=1.05 , 95 % CI=1.01 , 1.08 ) and by 7.7 % for each additional resistance training session ( OR=1.08 , 95 % CI=1.02 , 1.14 ) . Analyses were conducted between August 19 , 2010 , and December 16 , 2011 . CONCLUSIONS No differences were seen between groups in smoking outcomes . The association between greater exercise participation and higher odds of quitting within the exercise condition suggests that the lack of between-group differences might be a result of poor compliance with the exercise program . TRIAL REGISTRATION This study is registered at clinical trials.govNCT01615380 Postcessation weight gain is of concern to many female cigarette smokers . A multidisciplinary treatment combining psychological , dietary , and exercise components followed a 2-week smoking cessation program . Participants were r and omly assigned to receive six follow-up relapse prevention sessions ( in a group format or in an individually tailored format ) directed by trained representatives from clinical psychology , dietary counseling , and exercise physiology . As predicted , abstinence rates were significantly higher among the individually tailored follow-up participants than among those assigned to the group follow-up condition at 3 and 6 months posttreatment . Differences between conditions in postcessation weight gain were not significant . However , the postcessation weight gain that did occur was significantly associated with subsequent smoking relapse in the group follow-up condition only AIMS To examine the acute effects of a guided relaxation routine ( body scan ) and isometric exercise on desire to smoke and tobacco withdrawal symptoms . DESIGN Experimental comparison of three conditions . PARTICIPANTS Forty-eight individuals reporting smoking > or = 10 cigarettes daily . INTERVENTION R and om assignment to one of three interventions delivered via a 10-minute audio : isometric exercise ( IE , n = 14 ) , body scanning ( BS , n = 18 ) or a reading about natural history ( control group , n = 16 ) . Interventions were delivered twice on the same day : in the laboratory , then in their ' normal ' environment . MEASUREMENTS Desire to smoke ( primary outcome ) and withdrawal symptoms were rated at pre-intervention and up to 30 minutes post-intervention . FINDINGS Controlling for baseline scores , post-intervention desire to smoke and withdrawal symptoms were significantly lower for IE and BS groups , compared with the controls , in both environments . There were no significant differences for IE versus BS . For desire to smoke , controlling for baseline values , ratings in the laboratory were significantly lower for IE and BS versus the control up to 30 minutes post-intervention . In the normal environment , these ratings were significantly lower only up to 5 minutes post-intervention . CONCLUSIONS Brief IE and BS interventions are effective for reducing desire to smoke and withdrawal symptoms in temporarily abstaining smokers . These interventions were found to be more effective in the laboratory than in the smoker 's normal environment , but this may be an artefact of there not being a sufficient ' wash-out ' period between interventions . These techniques may be beneficial for managing desire to smoke and tobacco withdrawal The process and outcome of a smoking cessation program using behavior therapy alone ( BT ) or behavior therapy plus the nicotine patch ( BTP ) was studied in 64 participants . Participants quit smoking on a target date after a period of ad libitum smoking , cognitive-behavior therapy preparing them for cessation , and behavioral rehearsal for high-risk situations , including stress management , and coping with negative affect . Abstinence was significantly higher for the BTP group versus the BT group from the end of behavioral treatment ( 79 % vs. 63 % ) through the 3-month follow-up ( p < .01 ) , with the effects weakening at the 6- ( p = .06 ) and 12-month marks ( p = 38 % vs. 22 % ) . More general distress was observed among BT versus BTP participants ( i.e. , increased withdrawal , tension , fatigue , and coping frequency with decreased coping effort ; coping-to-urge ratio ) . The coping behavior of the BTP group may have been more effective than that of the BT group , as indicated by their significantly higher level of self-efficacy This study investigated both acute and longer term ( " chronic " ) effects of vigorous exercise training on affect , nicotine withdrawal , and cigarette craving among women enrolled in a smoking cessation research study . All subjects participated in a 12-week cognitive behavioral smoking cessation program and were r and omly assigned to attend three sessions per week of either a vigorous exercise program or contact control . Measures of positive and negative affect , cigarette craving , and nicotine withdrawal were administered immediately before , and again immediately after the final exercise or contact session each week of the program . Study I enrolled 24 women who had been assigned to the exercise condition . Significant reductions in negative affect , nicotine withdrawal and cigarette craving were observed following exercise most weeks of the program . No significant changes in positive affect were observed . In Study II this protocol was repeated among 62 women ( 44 exercise , 18 contact control ) in two consecutive cohorts of the larger study . Significant reduction were observed in negative affect , nicotine withdrawal and cigarette craving during most weeks of the program among exercise subjects but not contact condition subjects . No chronic ( baseline to posttreatment ) changes in positive or negative affect , cigarette craving or withdrawal symptoms were observed in either study . Vigorous exercise appears to produce acute improvements in withdrawal symptoms , cigarette craving , and negative affect among sedentary women attempting to quit smoking INTRODUCTION Depressive symptoms negatively impact smoking abstinence . However , few interventions have been targeted to smokers with current depression . Exercise improves mood and may benefit depressed smokers . This pilot study investigated the feasibility of an exercise intervention for depressed female smokers ( Center for Epidemiological Studies Depression Scale [ CES-D ] score > or = 16 ) . METHODS Participants ( M = 41 years , 98 % White ) were r and omized to 10 weeks of individually delivered exercise counseling ( n = 30 ) or a health education contact control condition ( n = 30 ) . All participants received nicotine patch therapy and behavioral counseling for smoking cessation . RESULTS The intervention was feasible as indicated by ability to recruit participants , exercise counseling session attendance ( M = 7.6 of 10 sessions attended ) , and significant increase in exercise frequency and stage of change from baseline to end of treatment ( EOT ) ( Week 10 ) . Participant attrition rate was 35 % by Week 10 but did not differ significantly between groups . Smoking abstinence rates at Week 10 , using intention-to-treat analysis , were 17 % for exercise counseling participants and 23 % for health education participants ( p = .75 ) . DISCUSSION An exercise counseling intervention was found to be feasible for depressed women smokers . More intensive intervention may be needed to increase smoking abstinence rates , and methods should be refined to reduce participant burden and attrition A review and meta- analysis by Hamer et al. ( 2006 ) showed that a single session of exercise can attenuate post-exercise blood pressure ( BP ) responses to stress , but no studies examined the effects among smokers or with brisk walking . Healthy volunteers ( n=60 ) , averaging 28 years of age and smoking 15 cigarettes daily , abstained from smoking for 2 h before being r and omly assigned to a 15-min brisk semi-self-paced walk or passive control condition . Subject characteristics , typical smoking cue-elicited cravings and BP were assessed at baseline . After each condition , BP was assessed before and after three psycho-social stressors were carried out : ( 1 ) computerised Stroop word – colour interference task , ( 2 ) speech task and ( 3 ) only h and ling a lit cigarette . A two-way mixed ANCOVA ( controlling for baseline ) revealed a significant overall interaction effect for time by condition for both systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) . Univariate ANCOVAs ( to compare between-groups post-stressor BP , controlling for pre-stressor BP ) revealed that exercise attenuated systolic BP and diastolic BP responses to the Stroop and speech tasks and SBP to the lit cigarette equivalent to an attenuated SBP and DBP of up to 3.8 mmHg . Post-exercise attenuation effects were moderated by resting blood pressure and self-reported smoking cue-elicited craving . Effects were strongest among those with higher blood pressure and smokers who reported typically stronger cravings when faced with smoking cues . Blood pressure responses to the lit cigarette were not associated with responses to the Stroop and speech task . A self-paced 15-min walk can reduce smokers ’ SBP and DBP responses to stress , of a magnitude similar on average to non-smokers This study was design ed to compare the effects of two aerobic training programmes of differing intensities on mood and mental well-being with those of a credible attention-placebo condition . One hundred and nine sedentary adult volunteers from the local population were assigned to four conditions : high intensity aerobic training , moderate intensity aerobic training , attention-placebo and waiting list . Training was carried out over a 10 week period . Subjects were assessed before and after training with psychological measures and the 12 min walk-run test , and follow-up evaluations were undertaken after 3 months . Ninety-four subjects began the programme and the adherence rate averaged 80 % , with no significant differences in number of drop-outs between conditions . Appropriate changes in estimated maximum oxygen consumption were observed in the three active conditions with the 12 min walk-run test . Psychological benefits were seen with the moderate exercise condition but not in the high exercise or attention-placebo conditions . These effects were manifest immediately after training on measures of tension/anxiety and confusion , and at follow-up on measures of perceived coping ability . The mechanisms underlying this pattern of results are discussed and the relative importance for health of vigorous activity and physical fitness is considered INTRODUCTION Recent studies have examined the effects of physical activity on craving to smoke and smoking withdrawal . The current study was design ed to compare and contrast the effects of 2 different forms of physical activity on general and cue-elicited craving to smoke . METHODS Following 1-hr nicotine abstinence , 76 daily smokers were r and omly assigned to engage in a 30-min bout of cardiovascular exercise ( CE ; brisk walk on a treadmill ) , Hatha yoga ( HY ) , or a nonactivity control condition . Participants completed measures of craving and mood , and a smoking cue reactivity assessment , before , immediately following , and approximately 20 min after the physical activity or control conditions . RESULTS Compared with the control condition , participants in each of the physical activity groups reported a decrease in craving to smoke , an increase in positive affect , and a decrease in negative affect . In addition , craving in response to smoking cues was specifically reduced among those who engaged in CE , whereas those who engaged in HY reported a general decrease in cravings . CONCLUSIONS This study provides further support for the use of exercise bouts for attenuating cigarette cravings during temporary nicotine abstinence . Results also suggest that CE can attenuate cravings in response to smoking cues . There are several areas for further research that may improve integration of exercise within smoking cessation treatment This was the first r and omized , controlled smoking cessation trial assessing the efficacy of an exercise intervention as an adjunct to nicotine gum therapy in comparison with both equal contact control and st and ard care control conditions . Sedentary female smokers aged 18 - 55 years were provided with nicotine gum treatment along with brief behavioral counseling and were r and omized into one of these three behavioral adjunct conditions . In the " intent-to-treat " sample ( N = 182 ) , at end of treatment and at 1-year follow-up , there were clear , but nonsignificant , trends in univariate analyses in which the exercise and equal contact control conditions both had higher rates of abstinence than the st and ard care control . However , when adjusting for other predictors of relapse in a multiple logistic regression , both exercise and equal contact control showed an advantage over st and ard care control in avoiding early relapse ( i.e. , after 1 week ) . In a multivariate survival model adjusting for other predictors , the equal contact condition had a significantly lower likelihood of relapse compared with the st and ard care condition and there was a near significant trend in which exercise offered an advantage over st and ard care as well . While these findings suggest a slightly improved likelihood of abstinence with exercise compared with st and ard care , exercise did not differ from equal contact control in its efficacy . Potential explanations for these equivalent levels of efficacy and implication s for the findings are discussed BACKGROUND Smoking often begins in early adolescence , and addiction can occur rapidly . For effective smoking prevention efforts with younger children , knowledge of their early smoking experience is needed . The purpose of this paper was to report the smoking experience of French elementary school children and to describe their lifestyle habits and health knowledge . METHODS A cross-sectional study of 913 children age 9 - 11 years in 31 r and omly selected schools of the Loire administrative department in France was conducted , using anonymous previously vali date d question naires . Correlates of smoking initiation and intention to smoke in the future were assessed by unconditional logistic regression analysis . RESULTS A total of 12.3 % of the children had smoked at least one cigarette , 5.1 % within the previous 30 days . Correlates of ever smoking were male sex , older age , engaging in physical activity , reporting not following safety-related recommendations , or drinking alcohol . Of the 112 children who reported ever smoking , 45.5 % stated that they did not want to remain smokers in the future and an additional 26.8 % were not sure . CONCLUSIONS Information on the smoking experience of preadolescents should help in design ing effective prevention programs , which are essential for reinforcing abstinence in nonsmokers and preventing others from progressing to addiction The effect of a minimal intervention strategy on maintenance of weight lost through either energy restriction alone or exercise alone during the previous year was studied in a sample of middle-aged men . At the end of the initial year of weight loss , dieters ( n = 44 ) and exercisers ( n = 46 ) were r and omly assigned to either an intervention condition , comprising monthly mailed informational packets and monthly to quarterly telephone contacts , or an assessment -only condition . The intervention had a significantly greater impact on weight maintenance in exercisers than it did in dieters . In addition , dieters showed a more variable pattern of weight gain and weight loss during the maintenance year than did exercisers . Based on 7-day food records and a 7-day physical activity recall question naire , exercisers reported a greater energy intake and a greater amount of time spent in vigorous activity relative to dieters at both the beginning and the end of the maintenance year . We conclude that exercise is easier to maintain in men using minimal contact strategies than dietary approaches to weight control focusing on modification of energy intake , with subsequent benefits in terms of both overall maintenance and stability of weight BACKGROUND The Commit to Quit trial was design ed to address the method ological problems of prior studies that have examined the contribution of exercise to smoking cessation . METHODS This paper provides an overview of the study design and describes the sample of women who participated in this trial ( N = 281 ) . Interrelationships among eating , exercise , and smoking behavior are examined . RESULTS Subjects r and omized into the study compared with the sample of women who completed the initial assessment but were not r and omized were more likely to be white , to have at least a high school education , and to smoke fewer cigarettes per day . Overall , the most frequent in eligibility criteria were health-related issues and scheduling conflicts . On average , participants in this study smoked more cigarettes per day than national sample s of women smokers . Significant interrelationships include the positive association of motivational readiness for quitting smoking and enhanced levels of dietary restraint and the positive association of motivational readiness for exercise adoption and high levels of weight concern . CONCLUSIONS This study represents the first adequately powered r and omized controlled clinical trial comparing the relative efficacy of a cognitive-behavioral smoking cessation treatment plus vigorous exercise with the same treatment plus contact control BACKGROUND Smoking prevalence rates among women are declining at a slower rate than among men . OBJECTIVE To determine if exercise , a healthful alternative to smoking , enhances the achievement and maintenance of smoking cessation . METHODS Two hundred eighty-one healthy , sedentary female smokers were r and omly assigned to either a cognitive-behavioral smoking cessation program with vigorous exercise ( exercise ) or to the same program with equal staff contact time ( control ) . Subjects participated in a 12-session , group-based smoking cessation program . Additionally , exercise subjects were required to attend 3 supervised exercise sessions per week and control subjects were required to participate in 3 supervised health education lectures per week . Abstinence from smoking was based on self-report , was verified by saliva cotinine level , and was measured at 1 week after quit day ( week 5 ) , end of treatment ( week 12 ) , and 3 and 12 months later ( 20 and 60 weeks after quit day , respectively ) . RESULTS Compared with control subjects ( n = 147 ) , exercise subjects ( n = 134 ) achieved significantly higher levels of continuous abstinence at the end of treatment ( 19.4 % vs 10.2 % , P = .03 ) and 3 months ( 16.4 % vs 8.2 % , P=.03 ) and 12 months ( 11.9 % vs 5.4 % , P=.05 ) following treatment . Exercise subjects had significantly increased functional capacity ( estimated VO2 peak , 25+/-6 to 28+/-6 , P<.01 ) and had gained less weight by the end of treatment ( 3.05 vs 5.40 kg , P = .03 ) . CONCLUSIONS Vigorous exercise facilitates short- and longer-term smoking cessation in women when combined with a cognitive-behavioral smoking cessation program . Vigorous exercise improves exercise capacity and delays weight gain following smoking cessation BACKGROUND Cross-sectional studies suggest that regular exercise has anti-inflammatory effects , leading to lower levels of several proatherogenic inflammatory markers . However , this has yet to be confirmed by r and omized prospect i ve trials . We performed a r and omized controlled trial to assess whether exercise training decreases levels of 5 inflammatory markers linked to future cardiovascular risk : white blood cell count , fibrinogen , C-reactive protein , soluble intercellular adhesion molecule 1 , and soluble CD40 lig and . METHODS One hundred fifty-two healthy female smokers were r and omized to either 12 weeks of exercise training or health education as part of a smoking cessation program . Smoking was held steady for the first 6 weeks , and thereafter , smoking cessation was actively attempted . One hundred four participants completed 6 weeks , and 88 completed 12 weeks . Fitness and circulating inflammatory marker levels were measured at baseline , 6 weeks , and 12 weeks . To avoid potential confounding from changes in smoking exposure during the second 6 weeks of the trial , the primary end point was change in inflammatory marker levels from baseline to 6 weeks . Change in inflammatory markers from baseline to 12 weeks was a secondary end point . RESULTS At baseline , greater physical fitness was associated with lower white blood cell , fibrinogen , and C-reactive protein levels , but these associations were not statistically significant after adjusting for body mass index ( P > .1 for all ) . Fitness improved significantly in the exercise group at both 6 and 12 weeks . However , there were no differences in levels of any inflammatory marker between the exercise and control groups at either 6 weeks ( primary end point ) or 12 weeks ( secondary end point ) ( P > .05 for all comparisons ) . CONCLUSION In female smokers , baseline associations between fitness and inflammatory markers were largely attributable to differences in body fat ; regular exercise did not reduce levels of any of the inflammatory markers studied despite a significant improvement in fitness at both 6 and 12 weeks This study examined the adherence rates and the effect of depression on adherence in two studies conducted among smokers with a past history of alcoholism . In both studies , subjects participated in a 12-session group-based exercise intervention for smoking cessation . The target quit date ( TQD ) was Session 8 . Participants in Study 1 were 73 smokers ( 43 % female ) . Exercise instructions began at Session 8 and continued through Session 12 . Mean frequency and number of minutes of exercise decreased during the 4 weeks of exercise treatment ( P<.001 ) . Study 2 , conducted with 18 smokers ( 50 % female ) , examined the feasibility of commencing exercise at Session 1 , well before the TQD . The mean number of minutes exercised increased from Sessions 1 to 12 ( P=.013 ) . In both studies , average session attendance was high ( 82 % ) . Combining subjects from both studies , depressed smokers at baseline reported greater mean frequency of exercise per week than nondepressed smokers ( P=.05 ) . The results suggest that depressed smokers can be engaged in an exercise program . Further research is needed to determine if commencing exercise early during treatment , prior to the TQD , improves adherence A total of 205 ( 113 male , 92 female ) nonhospitalized recovering alcoholics with > 3 months of continuous abstinence from alcohol and drugs and relatively heavy tobacco dependence ( Fagerstrom Tolerance Question naire score = 7.7 ; mean number of cigarettes per day , 26.8 ; mean number of years smoked , 24.4 ) were r and omized to st and ard treatment ( ST ) American Lung Association quit program plus nicotine anonymous meetings ( n = 70 ) , behavioral counseling plus physical exercise ( BEX ; n = 72 ) , or behavioral counseling plus nicotine gum ( BNIC ; n = 63 ) . A 3 x 4 repeated measures design was used to evaluate the effectiveness of the interventions on smoking outcome at baseline , posttreatment , and 6- and 12-month follow-ups . Self-reported smoking status was verified with biochemical and informant report . Verified self-report indicated that significantly more smokers in BEX quit by posttreatment ( 60 % ) than in either BNIC ( 52 % ) or ST ( 31 % ) , chi 2 ( 2 , N = 205 ) = 17.85 , p < .01 , but not at the 6-month ( 29 % , 27 % , and 21 % , respectively ) or 12-month ( 27 % , 27 % , and 26 % , respectively ) follow-up . Only 4 % ( 7 of 188 ) relapsed to alcohol or drugs . Alcohol relapse did not differ by treatment group or smoking status . Length of alcohol abstinence was not associated with smoking cessation outcome Abstract . There has been little research on smoking cessation after critical illness . Smokers make up a high percentage of patients admitted to intensive care ( ICU ) and stopping smoking is one message that should be clearly given to recovering patients . The recovery period provides an important opportunity for patients to quit smoking as the period of sedation and ventilation allows patients to start nicotine withdrawal . Smoking cessation advice was included in a 6-week self-help ICU rehabilitation package comprising information and an exercise programme . Recovering ICU patients were r and omised to receive either the routine follow-up of ward visits and ICU clinic appointments or routine follow-up plus the ICU rehabilitation package . Twenty out of thirty-one intervention patients and 16/30 control patients were smokers pre-ICU admission . At the 6-month follow-up , previous smokers given the rehabilitation package had a relative risk reduction for smoking of 89 % ( CI 98%–36 % ) . Smoking cessation after critical illness is aided by the provision of a rehabilitation programme Abstinence from smoking is associated with increased cravings , risk of accidents and self‐reported poor concentration . A single exercise session can reduce cravings and self‐reported poor concentration and can enhance cognitive performance among non‐smokers OBJECTIVE Previous studies have shown that exercise acutely reduces desire to smoke and withdrawal symptoms among adult smokers ; however , no study has examined these effects in younger smokers . This study investigated the impact of a short bout of moderate intensity exercise on desire to smoke , withdrawal symptoms and exercise-induced affect in temporarily abstinent adolescent smokers . METHODS Thirty-seven low-active male and female smokers aged 16 - 19 years , abstained from smoking overnight and were assigned to either ( i ) 10 min of moderate intensity cycle ergometry ( n=18 ) or ( ii ) a placebo control condition that involved very light intensity cycle ergometry ( n=19 ) . Measures of desire to smoke , the Mood and Physical Symptoms Scale ( MPSS ) and Subjective Exercise Experience Scale ( SEES ) were administered at baseline , 5 min during , 5 min after and 30 min after both conditions . RESULTS AND CONCLUSION A significant interaction effect for group by time was recorded for psychological distress scores , when the baseline value was covaried . Follow-up tests indicated that the exercise group reported significantly higher PD scores than the placebo control during exercise , but not at any other time point . No other significant effects were found for any other variables . Unlike research involving adult population s , a short bout of moderate intensity exercise did not alter desire to smoke among abstaining adolescent smokers and may negatively impact affective responses during exercise This study assessed the effect of short-term ( 2-week ) smoking abstinence on weight gain , energy intake , and physical activity in 60 postmenopausal women . Participants were stratified by their use of hormone replacement therapy ( HRT ; currently taking/not taking ) and then r and omized to abstinence or continued smoking for 2 weeks . The 30 abstainers gained a mean of 1.28 kg , compared with a 0.54 kg loss for the 30 continued smokers ( P=.002 ) . The abstainers also reported a significantly greater increase than did the smokers in total kilocalorie and in carbohydrate consumption for both weeks . There were no changes in physical activity and HRT effect . These are the first published findings on caloric intake and weight gain during smoking abstinence in postmenopausal women-an understudied population in the smoking cessation literature Rationale A previous study found that a 10-min bout of moderate intensity exercise reduced cigarette withdrawal symptoms and desire to smoke in sedentary smokers but the effect may have been due to participants focusing attention on physical activity rather than the activity itself . Objectives This study examined the effect of 5 min of moderate intensity exercise and 5 min of light intensity exercise on tobacco withdrawal symptoms amongst sedentary smokers . Methods Eighty-four smokers attended a laboratory session having abstained from smoking for between 11 and 14 h. Participants were r and omly allocated to one of three conditions : ( i ) light intensity exercise [ n=28 ; 10–20 % of heart rate reserve ( HRR ) ] ; ( ii ) moderate intensity exercise ( n=28 ; 40–60 % HRR ) , ( iii ) a passive control condition ( n=28 ) . Both exercise conditions involved 5 min of stationary cycling and participants rated tobacco withdrawal symptoms and cravings immediately before exercise ( baseline ) , during exercise at 2.5 min , immediately following exercise , then after 5 and 10 min of rest . Control participants made the same ratings across an equivalent time period . Results For moderate intensity exercise compared to light intensity exercise and control there was a significant reduction in strength of desire to smoke , relative to baseline , both during exercise and up to 5 min post-exercise . Relative to baseline , there were also significant reductions in restlessness , stress , tension and poor concentration at 5 and 10 min post-exercise , for moderate intensity exercise compared to light intensity exercise and control . Conclusions Five minutes of moderate intensity exercise is associated with a short-term reduction in desire to smoke and tobacco withdrawal symptoms . Very brief bouts of exercise may therefore be useful as an aid to smoking cessation INTRODUCTION To address the lack of smoking cessation programs available to young adults , Stop My Smoking ( SMS ) USA , a text messaging-based smoking cessation program , was developed and pilot tested . METHODS This was a two-arm r and omized controlled trial with adaptive r and omization ( arms were balanced by sex and smoking level [ heavy vs. light ] ) , conducted nationally in the United States . One hundred sixty-four 18- to 25-year-old daily smokers who were seriously thinking about quitting in the next 30 days were r and omized to either ( a ) the 6-week SMS USA intervention ( n = 101 ) or ( b ) an attention-matched control group aim ed at improving sleep and physical activity ( n = 63 ) . The main outcome measure was 3-month continuous abstinence , verified by a significant other . Participants but not research ers were blinded to study arm allocation . RESULTS Based upon intent-to-treat analyses , intervention participants ( 39 % ) were significantly more likely than control participants ( 21 % ) to have quit at 4 weeks postquit ( adjusted odds ratio [ aOR ] = 3.33 , 95 % confidence interval [ CI ] : 1.48 , 7.45 ) . Findings were not sustained at 3 months postquit , although rates in the SMS USA group were favored ( 40 % vs. 30 % , respectively ; aOR = 1.59 , 95 % CI : 0.78 , 3.21 ) . Subsequent analyses suggested that among intervention participants , SMS USA might be more influential for youth not currently enrolled in a higher education ( p = .06 ) . CONCLUSIONS Consistent with pilot studies , the sample was underpowered . Data suggest , however , that the SMS USA program affects smoking cessation rates at 4 weeks postquit . More research is needed before conclusions can be made about long-term impact . Identifying profiles of users for whom the program may be particularly beneficial also will be important A brief bout of aerobic exercise ( e.g. stationary bicycle ) has been shown to result in an acute reduction in tobacco withdrawal symptoms and cravings in abstinent smokers . However , aerobic exercise is often not practical and it is of interest to examine whether non-aerobic exercise has a similar effect . We investigated whether isometric exercise ( involving muscular contractions against resistance without movement , e.g. placing the palms of the h and s together and pushing ) reduces desire to smoke and tobacco withdrawal symptoms . Following overnight abstinence smokers were r and omized to 5-min of : isometric exercises ( n = 20 ) , body scanning ( focusing attention on sensations in different areas of the body , n = 20 , control ) , or sitting passively ( n = 20 , control ) . Desire to smoke and tobacco withdrawal symptoms ( ' irritable ' , ' depressed ' , ' stressed ' , ' tense ' , ' restless ' and ' poor concentration ' ) were rated at baseline , immediately post-intervention , and 5- , 10- , 15- and 20-min post-intervention . Isometric exercise produced a significantly greater reduction in desire to smoke versus passive control at immediate post-intervention and 5-min post-intervention , relative to baseline ( p < 0.05 ) . Most withdrawal symptoms were significantly moderated by exercise versus controls at some point between 5- to 20-min post-intervention , relative to baseline ( p < 0.05 ) . Brief isometric exercise has potential for offering immediate relief from a desire to smoke Previous r and omized controlled trials have not supported moderate intensity exercise as an efficacious adjunct to smoking cessation treatments for women ; however , compliance with exercise programs in these studies has been poor . The purpose of this pilot study was to estimate the effects of moderate intensity exercise on smoking cessation outcomes under optimal conditions for exercise program compliance . Sixty previously sedentary , healthy , female smokers were r and omized to an 8-week program consisting of brief baseline smoking cessation counseling and the nicotine patch plus either 150 min/week of moderate intensity exercise or contact control . Participants attended a median of 86.4 % and 95.5 % of prescribed exercise/control sessions , respectively . There was a moderate , though statistically nonsignificant , effect of exercise at post-treatment for objective ly verified 7-day point prevalence abstinence ( 48.3 % vs. 23.3 % ; OR = 3.07 , 95 % CI : 0.89 - 11.07 ) and prolonged abstinence ( 34.5 % vs. 20.0 % ; OR = 2.11 , 95 % CI : 0.56 - 8.32 ) . Effects were attenuated when controlling for potential confounders , and after a 1-month , no-treatment period . The findings provide a preliminary indication that , given adequate compliance , moderate intensity exercise may enhance short-term smoking cessation outcomes for women ; however , a larger trial is warranted The present study aim ed to shed light on contradictory findings about the effects of exercise on negative affect during smoking cessation . The authors hypothesized that smoking-specific weight concern would moderate the relationship between exercise and negative affect . Baseline measures of smoking-specific weight concern , exercise , and negative affect were completed by 146 women participating in a r and omized controlled trial of smoking cessation plus weight control . Exercise and negative affect were reassessed 1 week after the quit date . Among women with heightened smoking-specific weight concern , greater engagement in exercise was associated with less of an increase in negative affect . Results suggest that exercise may help temper negative affect states for women with heightened smoking-specific weight concern Latinas with type 2 diabetes are in need of culturally sensitive interventions to make recommended long-term lifestyle changes and reduce heart disease risk . To test the longer-term ( 24-month ) effects of a previously successful , culturally adapted , multiple-health-behavior-change program , ¡ Viva Bien ! , 280 Latinas were r and omly assigned to usual care or ¡ Viva Bien!. Treatment included group meetings to promote a culturally adapted Mediterranean diet , physical activity , supportive re sources , problem solving , stress-management practice s , and smoking cessation . ¡ Viva Bien ! participants achieved and maintained some lifestyle improvements from baseline through 24 months , including significant improvements for psychosocial outcomes , fat intake , social – environmental support , body mass index , and hemoglobin A1c . Effects tended to diminish over time . The ¡ Viva Bien ! multiple-behavior program was effective in improving and maintaining some psychosocial , behavioral , and biological outcomes related to heart health across 24 months for Latinas with type 2 diabetes , a high-risk , underserved population ( Clinical Trials.gov number , NCT00233259 ) Abstract . Rationale : Previous research suggests that a long bout of vigorous intensity exercise may reduce tobacco withdrawal symptoms and desire to smoke during abstinence . Objective : In the present study , we investigated whether a short bout of moderate intensity exercise reduced desire to smoke and withdrawal symptoms in abstaining smokers . Methods : Seventy-eight smokers attended the laboratory in the afternoon having not smoked since the previous evening . They rated their desire to smoke and withdrawal symptoms immediately before , during and after 10 min of moderate intensity exercise on a stationary cycle ( experimental condition ) , or after waiting passively ( control condition 1 ) or watching a video ( control condition 2 ) . Results : Ratings of desire to smoke and withdrawal symptoms decreased more in the experimental group than in both control groups , which did not differ from each other . The effect was evident at all measurement points and was maintained for at least 10 min following exercise . Conclusion : A single bout of 10 min of moderate intensity exercise has a rapid and measurable effect on desire to smoke and tobacco withdrawal symptoms in abstaining smokers . Short bouts of exercise may be useful in helping to reduce desire to smoke and withdrawal symptoms during smoking cessation AIMS To control for familial confounds , we studied the association between adolescent physical activity and later smoking in twin siblings discordant for their baseline physical activity . DESIGN AND MEASUREMENTS In this prospect i ve population -based twin study , we asked whether persistent physical activity/inactivity in adolescence ( assessed at 16 , 17 and 18.5 years ) predicted question naire-reported daily smoking at ages 22 - 27 . Twins who , on the three baseline question naires , consistently reported frequent leisure physical activity ( more than three times weekly ) were classified as persistent exercisers , those who exercised less than three times monthly were called persistently inactive , others were occasional exercisers . SETTING Finl and . PARTICIPANTS A total of 4240 individuals , including 1870 twin pairs . Findings In analyses of individual twins , compared to persistent activity , persistent physical inactivity predicted increased risk of daily smoking ( age- and sex-adjusted odds ratio 5.53 , 95 % confidence interval 3.88 - 7.88 , P < 0.001 ) . The risk remained elevated even after excluding all those who had smoked 50 cigarettes or more life-time at baseline and adjusted for educational level in adolescence . In within-pair analyses compared to the active members of discordant twin pairs , the physically inactive co-twins had increased risk of future daily smoking ( sex-adjusted odds ratio 3.39 , 95 % confidence interval 1.56 - 7.39 , P = 0.002 ) . CONCLUSIONS Persistent physical inactivity in adolescence relates to adult smoking , even after familial factors are taken into account The effects of physical activity as a maintenance strategy for smoking cessation were evaluated . After a st and ard smoking cessation program , forty-two women were r and omly assigned to one of three groups that received equal number of maintenance meetings : a physical activity program , smoking habit change information and contact control . Abstinence decreased from 83 % at the end of treatment to 73 % at 3 months , 49 % at six months and 34 % at 18 months . No differences were shown in cessation across groups . Group differences were shown for subjective levels of tension-anxiety , those who exercised showed increased tension anxiety levels compared to subjects in the no activity groups A comparison was carried out of the psychological effects of a moderate aerobic training programme ( n = 24 ) and an attention-placebo strength and flexibility training programme ( n = 23 ) in previously inactive anxious adults from the general population . Training consisted of one supervised and three unsupervised sessions per week for 10 weeks . Effects were assessed with the Profile of Mood States , the State-Trait Anxiety Inventory and question naires indexing perceived coping ability . Seven participants dropped out of each condition during the training period . Expectations of benefit assessed pre-training , and satisfaction assessed post-training , did not differ between conditions . The moderate exercise programme led to significant improvements in aerobic fitness , and was associated with significantly greater reductions in tension-anxiety , depression and other moods than the attention-placebo condition , together with increases in perceived ability to cope with stress . Psychological responses were not correlated with changes in fitness assessed with bicycle ergometry or the 12 min walk/run test . These effects were maintained on 3 month follow up Most cessation studies assume that dropouts are smokers . Instead , the authors analyzed these outcomes separately using multinomial regression to model the relative risk of quitting versus continued smoking and dropping out . Female ( N = 281 ) smokers were r and omly assigned to a 12-week smoking cessation program plus either a 3-times-per-week exercise program or a contact control wellness program . Higher body mass index and longer prior quit attempts predicted cessation . Self-efficacy was associated with a lower likelihood of dropout . Greater nicotine dependence and lower education predicted continued smoking or dropout versus quitting among exercisers . Patterns of smoking , dropping out , and quitting between Weeks 5 and 12 were different between exercisers and controls . Dropouts should be considered as a separate category from smokers 2 . When an image on the Film is obliterated with a round black mark , it is an indication o f either blurred copy because o f movement during exposure , duplicate copy , or copyrighted material s tha t should no t have been filmed . For blurred pages , a good image o f the page can be found in the adjacent frame . If copyrighted material s were deleted , a target note will appear listing the pages in the adjacent frame . The factors predicting smoking abstinence in depressive smokers , and the role of physical activity in precessation , were investigated . One hundred thirty-three smokers with current major depressive disorders ( score ≥10 on the Depression subscale of Hospital Anxiety and Depression Scale ) were recruited from a large prospect i ve cohort of smokers ( n = 1,119 ) . Over a maximum period of 3 years , regression modeling , adjusted for potential confounders , showed that physical activity was associated with relapse ( relapse rate = 0.54 , 95 % confidence interval = 0.34 - 0.85 , p = .008 ) . Also , antidepressants , anxiolytics , level of education , and number of attempts to quit were associated with relapse . The protective role of physical activity on relapse rate could be a modifiable factor in smoking cessation for smokers with depressive disorders There is some evidence to suggest that regular supervised physical activity may be useful as an aid to smoking cessation . It is unclear whether less extensive interventions confer similar benefits . This study examined whether physical activity counseling alone increases long-term smoking abstinence and physical activity levels and reduces weight gain . 299 male and female smokers were r and omized to a 7-week smoking cessation program , including nicotine replacement therapy , plus either ( i ) physical activity counseling ( ' exercise ' , N=154 ) , or ( ii ) health education advice ( ' control ' , N=145 ) . There was no significant difference in rates of continuous smoking abstinence between the exercise group and the controls at 12 months following the quit day ( 9.1 % versus 12.4 % ) . Significant increases in physical activity levels observed for the exercise group versus the controls at six weeks were not maintained at 12 months . There was a non-significant tendency for less weight gain in the exercise group versus the controls at 12 months ( P=0.06 ) . Further trials are needed to examine the effect of more extensive physical activity interventions on smoking cessation , physical activity levels and post-cessation weight gain Many smokers perceive that smoking controls their body weight and that stopping smoking leads to weight gain . This study examined characteristics associated with weight concerns in 72 male smokers enrolled in a controlled trial for smoking cessation . Motivation to quit smoking was found to be significantly lower in those with weight concerns ( P < .001 ) . Further investigation is needed to enable the tailoring of interventions for weight-concerned male smokers AIMS AND DESIGN Moderate-intensity exercise has been shown to reduce common smoking withdrawal symptoms and desire to smoke in acutely abstinent smokers . The aim of the present study was to determine if this was caused by distraction . A secondary aim was to determine whether exercise-related changes in affect were related to a reduction in symptoms . METHODS Forty ' sedentary ' participants who had smoked at least 10 or more cigarettes per day for at least 3 years were assigned r and omly to one of two groups . They completed either 10 minutes of moderate-intensity exercise on a stationary bicycle ergometer or 10 minutes of a cognitive distraction task ( paced visual serial addition task , PVSAT ) after 11 - 15 hours of smoking abstinence . Participants rated smoking withdrawal symptoms and desire to smoke using st and ard scales at 10 , 5 and 0 minutes before the experimental intervention , then at 5 and 10 minutes after the start of the intervention and 5 and 10 minutes after its completion . FINDINGS Significant group x time interactions were observed for ratings of desire to smoke and several withdrawal symptoms ( irritability , depression , restlessness , difficulty concentrating and stress ) . There was a reduction in ratings during and immediately following exercise that was not observed with cognitive distraction . Also it was found the effects were not mediated by changes in affect observed in the exercise condition . CONCLUSIONS A brief bout of moderate-intensity exercise can lead to a rapid reduction in desire to smoke and withdrawal discomfort , which is not due to the distracting effect of exercise or the effects of mood . These findings support recommendations to smokers to use exercise as a means of helping cope with the difficulties encountered when they try to stop Evidence suggests that vigorous-intensity exercise interventions may be effective for smoking cessation among women ; however , few studies have examined the efficacy of a moderate-intensity exercise program . The present study examined the efficacy of moderate-intensity exercise for smoking cessation among female smokers . Healthy , sedentary female smokers ( N = 217 ) were r and omly assigned to an 8-week cognitive-behavioral smoking cessation program plus moderate-intensity exercise ( CBT+EX ) or to the same cessation program plus equal contact ( CBT ) . A sub sample received nicotine replacement therapy . Results indicated that the CBT+EX and CBT groups were equally likely to attain smoking cessation at the end of treatment , as measured by cotinine-verified 7-day point-prevalence abstinence ( 20.2 % for CBT+EX vs. 18.5 % for CBT ) . The CBT+EX group was more likely to report smoking cessation , as measured by 7-day point prevalence at the 3-month follow-up ( 11.9 % vs. 4.6 % , p<.05 ) , compared with the CBT group . No group differences were found at 12 months by either 7-day point prevalence ( 7.3 % for CBT+EX vs. 8.3 % for CBT ) or continuous abstinence ( 0.9 % for CBT+EX vs. 0.9 % for CBT ) . Additionally , among participants in the CBT+EX group , those with higher adherence to the exercise prescription were significantly more likely to achieve smoking cessation at the end of treatment than were participants reporting lower adherence to exercise . Our findings indicate that the empirical support for moderate-intensity exercise as an adjunctive treatment to CBT for smoking cessation may be limited . Perhaps future studies could compare moderate- vs. vigorous-intensity physical activity to test their relative efficacy Cigarette smoking continues to be the leading preventable cause of chronic illness in the United States . A high percentage of smokers attempt to quit each year ; however , smoking cessation success rates are low . Adding an exercise program to traditional therapies can increase smoking cessation rates among women . An experimental design was used to test two hypotheses . The first was that women who engage in a multifaceted approach to smoking cessation that includes a structured exercise program , nicotine replacement therapy ( NRT ) , and weekly counseling sessions will experience less weight gain during an 8-week smoking cessation program and at the 4-month follow-up session than women who engage in NRT and weekly counseling sessions alone . The second was that women who engage in a structured exercise program with NRT and weekly counseling sessions will have higher smoking cessation rates at the end of the 8-week smoking cessation program and at the 4-month follow-up session than women who engage in NRT and weekly counseling sessions alone This study assessed the effect of treating nicotine dependence in smokers undergoing inpatient treatment for other addictions . It was a prospect i ve , nonr and omized , controlled trial with a 1-year outcome . The subjects were smoking patients ( 50 controls , 51 in intervention group ) in an inpatient addictions treatment unit in a medical center . The enrollment of subjects was sequential : controls were enrolled first ; after a 6-week washout period , intervention subjects were enrolled . Controls received usual care , and the intervention group received nicotine dependence treatment consisting of a consultation , 10 intervention sessions , and a structured relapse prevention program . Smoking cessation rate and abstinence from alcohol or other drug use were the main outcome measures . The confirmed smoking cessation rate at 1 year was 11.8 % in the intervention group and 0.0 % in the control group ( p = 0.027 ) . Nicotine dependence intervention did not seen to interfere with abstinence from alcohol or other drugs ( 1-year relapse rate was 31.4 % in the intervention group and 34.0 % in controls ) . In this study , nicotine dependence treatment provided as part of addictive disorders treatment enhanced smoking cessation and did not have a substantial adverse effect on abstinence from the nonnicotine drug of dependence Quitting smoking often results in weight gain . The causes of the gain are not known . The present study evaluated changes in calories , total sugars , sucrose , fat , protein , and nonsugar carbohydrates as well as changes in activity levels after quitting smoking . Ninety-five subjects were r and omly assigned to either early ( Week 2 ) or late ( Week 6 ) quit date s. Subjects were assessed on weight , food intake , activity levels , and smoking levels at baseline , at Weeks 4 and 8 , and at Weeks 12 and 26 postquit . The results indicated significant increases in calories , sucrose , and fats 2 weeks after the quit date . Changes for total sugars were less consistent . Activity levels did not change significantly . Early caloric increases predicted weight gain at 26 weeks for abstinent women . No relation was found for abstinent men , but interpretation of this finding is weakened by a small sub sample size . Abstinent subjects gained over 9 lb by 26 weeks postquit . Despite this gain , Week 26 results showed that caloric intake for abstinent women was approximately equal to that observed at baseline , whereas that for abstinent men had dropped significantly We examined the effects of physical exercise on smoking relapse . Twenty previously sedentary female smokers were r and omly assigned to smoking cessation plus exercise or smoking cessation with frequency contact control . The smoking cessation program included 12 professionally led sessions over 12 weeks . Exercise treatment included three supervised exercise sessions per week for 15 weeks . Contact control included three women 's health/wellness lectures per week for 15 weeks . Smoking abstinence was vali date d by carbon monoxide and saliva cotinine . Mean exercise attendance for exercise subjects was 88 % with an increase in estimated VO2 of 25 % . The percentage of subjects who quit for 24 hours was 80 % for the exercise and 90 % for the contact group . One subject in the contact group remained abstinent at the end of the 12-week treatment and at 1- , 3- , and 12-month follow-ups , whereas three subjects in the exercise group were abstinent at these time points . These results suggest that exercise training improves short-term quit rates and may prove a useful strategy for long-term maintenance of smoking cessation AIMS To examine prospect ively continuity and change in smoking behaviour and associated attributes over a 10-year period . DESIGN , SETTING AND PARTICIPANTS Participants ( initially aged 18 - 23 years ) in the Australian Longitudinal Study on Women 's Health completed postal question naires in 1996 , 2000 , 2003 and 2006 . The analysis sample was 6840 women who participated in all surveys and provided complete smoking data . MEASUREMENTS Outcome variables were transitions in smoking behaviour between surveys 1 and 2 , 2 and 3 , 3 and 4 and 1 and 4 . Attributes that differentiated continuing smokers from quitters , relapsers from ex-smokers and adopters from never smokers were examined for each survey period . Explanatory variables included previous smoking history , demographic , psychosocial , life-style risk behaviour and life-stage transition factors . FINDINGS Over 10 years , 23 % of participants either quit , re-started , adopted or experimented with smoking . Recent illicit drug use and risky or high-risk drinking predicted continued smoking , relapse and smoking adoption . Marriage or being in a committed relationship was associated significantly with quitting , remaining an ex-smoker and not adopting smoking . Living in a rural or remote area and lower educational attainment were associated with continued smoking ; moderate and high physical activity levels were associated positively with remaining an ex-smoker . CONCLUSIONS Life-style and life-stage factors are significant determinants of young women 's smoking behaviour . Future research needs to examine the inter-relationships between tobacco , alcohol and illicit drug use , and to identify the determinants of continued smoking among women living in rural and remote areas . Cessation strategies could examine the role of physical activity in relapse prevention OBJECTIVES For smoking cessation , physical activity ( PA ) may help manage withdrawal symptoms , mood , stress , and weight ; yet studies of PA as an aid for smoking cessation have been mixed . This study examined : ( 1 ) the impact of an extended relapse prevention program on increasing moderate to vigorous PA ( MVPA ) in adults enrolled in a tobacco cessation treatment trial ; ( 2 ) whether changes in MVPA were associated with sustained abstinence from smoking ; and ( 3 ) mechanisms by which MVPA may support sustained abstinence from smoking . METHODS In a r and omized controlled trial conducted from 2003 - 2006 in San Francisco , California , 407 adult smokers received a 12 week group-based smoking cessation treatment with bupropion and nicotine patch with the quit date set at week 3 . At week 12 , participants were r and omized to no further treatment or to 40 weeks of bupropion or placebo with or without an 11-session relapse prevention intervention of which 2 sessions ( held at weeks 16 and 20 ) focused on PA . Participants receiving the PA intervention ( n=163 ) received a pedometer , counseling to increase steps 10 % biweekly towards a 10,000 steps/day goal , and personalized reports graphing progress with individualized goals . The International Physical Activity Question naire assessed weekly minutes of MVPA at baseline and weeks 12 and 24 . Sustained abstinence from tobacco at week 24 was vali date d with expired carbon monoxide . RESULTS In a repeated mixed model analysis , intervention participants significantly increased their MVPA relative to control participants , F(1,475)=3.95 , p=.047 . Pedometer step counts also increased significantly , t(23)=2.36 , p=.027 , though only 15 % of intervention participants provided 6 weeks of pedometer monitoring . Controlling for treatment condition , increased MVPA predicted sustained smoking abstinence at week 24 , odds ratio=1.84 ( 95 % CI : 1.07 , 3.05 ) . Among participants with sustained abstinence , increased MVPA was associated with increased vigor ( r=0.23 , p=.025 ) and decreased perceived difficulty with staying smoke-free ( r=-0.21 , p=.038 ) . CONCLUSION PA promotion as an adjunct to tobacco treatment increases MVPA levels ; changes in MVPA predict sustained abstinence , perhaps by improving mood and self-efficacy The association of physical activity to the initiation of health risk behaviors was examined in a 3-yr prospect i ve study of a population -based cohort of 1245 adolescents aged 12 - 16 yr . Four hundred thirty-seven students ( 35 % of the cohort ) were identified at baseline via self-report survey as never having smoked cigarettes , consumed alcohol , used marijuana , or carried a weapon . Three measures of physical activity were obtained at baseline : leisure-time physical activity ( LTPA ) , level of aerobic fitness ( AF ) , and participation in competitive athletics . Significant associations , with notable gender differences , were observed between physical activity and the initiation of cigarette smoking and alcohol use . The cumulative proportion of male students initiating alcohol use was 48 % , 42 % , and 24 % for high , moderate , and low LTPA , respectively ( P < 0.01 ) . Males who participated in competitive athletics were significantly more likely than nonathletes to initiate alcohol use ( 44 % vs 17 % , P < 0.01 ) . The cumulative proportion of female students initiating cigarette use was 10 % , 23 % , and 22 % for high , moderate , and low LTPA , respectively ( P < 0.05 ) and 7 % , 28 % , and 16 % for high , moderate , and low AF , respectively ( P < 0.05 ) . No association was found between physical activity and weapon carrying . These results indicate that in this cohort of adolescents , the most active or most fit females were less likely to initiate cigarette smoking . In contrast , the most active males or males who participated in competitive athletics appeared more at-risk for initiating alcohol consumption than their less active counterparts We evaluated in a r and omized prospect i ve trial the possible effect of smoking cessation on exercise performance in middle-aged female smokers who underwent vigorous exercise training as an adjunct to a cognitive-behavioral smoking cessation treatment program . A total of 109 subjects met the criteria for this sub study ; of these , 51 were in the contact control ( nonexercising ) group and 58 were in the exercise training group . Both groups had a grade d maximal exercise stress test performed on a bicycle ergometer before and after 12 weeks of treatment . All subjects participated in a 12-session , group-based , cognitive-behavioral treatment program for nicotine dependence . Subjects in the contact condition participated in 3 supervised health education lectures per week but did not engage in regular exercise . Subjects in the exercise group trained 3 times a week , averaging 83 % of maximum heart rate achieved on their baseline exercise test . On the 12-week exercise stress test , the exercise group did significantly better than control in all aspects of exercise performance . Those who quit showed a further increase in their exercise test duration ( p < 0.001 ) and had a greater increase in calculated peak oxygen consumption expressed as fat-free weight ( p = 0.031 ) . In conclusion , women who undergo a vigorous exercise training program and quit smoking demonstrate improved exercise performance over those who continue to smoke |
771 | 32,152,435 | ABI-to-ENZ sequential therapy in patients with CRPC was associated with better PFS , PSA – PFS , and PSA response rates .
Regardless of sequencing , response to drug therapy was transient for both ABI and ENZ when either agent was used as a secondary therapy . | This systematic review and meta- analysis aim ed to assess the prognostic value of sequential of abiraterone ( ABI ) and enzalutamide ( ENZ ) therapy in patients with castration-resistant prostate cancer ( CRPC ) . | BACKGROUND Enzalutamide ( formerly called MDV3100 ) targets multiple steps in the and rogen-receptor-signaling pathway , the major driver of prostate-cancer growth . We aim ed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy . METHODS In our phase 3 , double-blind , placebo-controlled trial , we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity . We r and omly assigned them , in a 2:1 ratio , to receive oral enzalutamide at a dose of 160 mg per day ( 800 patients ) or placebo ( 399 patients ) . The primary end point was overall survival . RESULTS The study was stopped after a planned interim analysis at the time of 520 deaths . The median overall survival was 18.4 months ( 95 % confidence interval [ CI ] , 17.3 to not yet reached ) in the enzalutamide group versus 13.6 months ( 95 % CI , 11.3 to 15.8 ) in the placebo group ( hazard ratio for death in the enzalutamide group , 0.63 ; 95 % CI , 0.53 to 0.75 ; P<0.001 ) . The superiority of enzalutamide over placebo was shown with respect to all secondary end points : the proportion of patients with a reduction in the prostate-specific antigen ( PSA ) level by 50 % or more ( 54 % vs. 2 % , P<0.001 ) , the soft-tissue response rate ( 29 % vs. 4 % , P<0.001 ) , the quality -of-life response rate ( 43 % vs. 18 % , P<0.001 ) , the time to PSA progression ( 8.3 vs. 3.0 months ; hazard ratio , 0.25 ; P<0.001 ) , radiographic progression-free survival ( 8.3 vs. 2.9 months ; hazard ratio , 0.40 ; P<0.001 ) , and the time to the first skeletal-related event ( 16.7 vs. 13.3 months ; hazard ratio , 0.69 ; P<0.001 ) . Rates of fatigue , diarrhea , and hot flashes were higher in the enzalutamide group . Seizures were reported in five patients ( 0.6 % ) receiving enzalutamide . CONCLUSIONS Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy . ( Funded by Medivation and Astellas Pharma Global Development ; AFFIRM Clinical Trials.gov number , NCT00974311 . ) Primary resistance to and rogen receptor (AR)-directed therapies in metastatic castration-resistant prostate cancer ( mCRPC ) is poorly understood . We r and omized 202 patients with treatment-naïve mCRPC to abiraterone or enzalutamide and performed whole-exome and deep targeted 72-gene sequencing of plasma cell-free DNA prior to therapy . For these agents , which have never been directly compared , time to progression was similar . Defects in BRCA2 and ATM were strongly associated with poor clinical outcomes independently of clinical prognostic factors and circulating tumor DNA abundance . Somatic alterations in TP53 , previously linked to reduced tumor dependency on AR signaling , were also independently associated with rapid resistance . Although detection of AR amplifications did not outperform st and ard prognostic biomarkers , AR gene structural rearrangements truncating the lig and binding domain were identified in several patients with primary resistance . These findings establish genomic drivers of resistance to first-line AR-directed therapy in mCRPC and identify potential minimally invasive biomarkers . Significance : Leveraging plasma specimens collected in a large r and omized phase II trial , we report the relative impact of common circulating tumor DNA alterations on patient response to the most widely used therapies for advanced prostate cancer . Our findings suggest that liquid biopsy analysis can guide the use of AR-targeted therapy in general practice . Cancer Discov ; 8(4 ) ; 444 - 57 . © 2018 AACR.See related commentary by Jayaram et al. , p. 392This article is highlighted in the In This Issue feature , p. 371 PURPOSE Persistent and rogen signaling is implicated in castrate-resistant prostate cancer ( CRPC ) progression . This study aim ed to evaluate and rogen signaling in bone marrow-infiltrating cancer and testosterone in blood and bone marrow and to correlate with clinical observations . PATIENTS AND METHODS This was an open-label , observational study of 57 patients with bone-metastatic CRPC who underwent transiliac bone marrow biopsy between October 2007 and March 2010 . Patients received oral abiraterone acetate ( 1 g ) once daily and prednisone ( 5 mg ) twice daily . And rogen receptor ( AR ) and CYP17 expression were assessed by immunohistochemistry , testosterone concentration by mass spectrometry , AR copy number by polymerase chain reaction , and TMPRSS2-ERG status by fluorescent in situ hybridization in available tissues . RESULTS Median overall survival was 555 days ( 95 % CI , 440 to 965 + days ) . Maximal prostate-specific antigen decline ≥ 50 % occurred in 28 ( 50 % ) of 56 patients . Homogeneous , intense nuclear expression of AR , combined with ≥ 10 % CYP17 tumor expression , was correlated with longer time to treatment discontinuation ( > 4 months ) in 25 patients with tumor-infiltrated bone marrow sample s. Pretreatment CYP17 tumor expression ≥ 10 % was correlated with increased bone marrow aspirate testosterone . Blood and bone marrow aspirate testosterone concentrations declined to less than picograms-per-milliliter levels and remained suppressed at progression . CONCLUSION The observed pretreatment and rogen-signaling signature is consistent with persistent and rogen signaling in CRPC bone metastases . This is the first evidence that abiraterone acetate achieves sustained suppression of testosterone in both blood and bone marrow aspirate to less than picograms-per-milliliter levels . Potential admixture of blood with bone marrow aspirate limits our ability to determine the origin of measured testosterone |
772 | 11,279,716 | Pelvic floor muscle training was better than no treatment or placebo treatments for women with stress or mixed incontinence . '
Intensive ' appeared to be better than ' st and ard ' pelvic floor muscle training .
There is insufficient evidence to determine if pelvic floor muscle training is better or worse than other treatments .
Evidence of the effect of adding other adjunctive treatments to PFMT ( e.g. vaginal cones , intravaginal resistance ) is equally limited .
The effectiveness of biofeedback assisted PFMT is not clear , but on the basis of the evidence available there did not appear to be any benefit over PFMT alone at post treatment assessment .
Long-term outcomes of pelvic floor muscle training are unclear .
Side effects of pelvic floor muscle training were uncommon and reversible .
REVIEW ER 'S CONCLUSIONS Pelvic floor muscle training appeared to be an effective treatment for adult women with stress or mixed incontinence .
Pelvic floor muscle training was better than no treatment or placebo treatments .
The limitations of the evidence available mean that is difficult to judge if pelvic floor muscle training was better or worse than other treatments .
Most trials to date have studied the effect of treatment in younger , premenopausal women . | BACKGROUND Pelvic floor muscle training is the most commonly recommended physical therapy treatment for women with stress leakage of urine .
It is also used in the treatment of women with mixed incontinence , and less commonly for urge incontinence .
Adjuncts , such as biofeedback or electrical stimulation , are also commonly used with pelvic floor muscle training .
The content of pelvic floor muscle training programmes is highly variable .
OBJECTIVES To determine the effects of pelvic floor muscle training for women with symptoms or urodynamic diagnoses of stress , urge and mixed incontinence , in comparison to no treatment or other treatment options . | In a prospect i ve r and omized study the efficiacy of physical therapy in female stress incontinence could be verified . The greatest success rate was achieved by medical gymnastics , whereas the perineal electrical stimulation should be used as supporting measure like a biofeedback mechanism because of its low effective intensity . Despite of the good therapeutic success ( 51.5 % ) with lasting effects no objective criteria to the use of physical therapy in female stress incontinence were found Fifty consecutive female patients with genuine urinary stress incontinence were r and omized either to surgery or to a pelvic floor training program . The operative procedure was chosen according to the type of bladder suspension defect on micturition cystourethrography . The training program was given 5 times in weekly lessons and the patients were guided by trained physiotherapists . Surgery was superior to the pelvic floor training program both subjectively and objective ly . However , a significant improvement was found following the training program . Forty-two percent were satisfied with the outcome of the training and did not want operation . We find physiotherapist-guided pelvic floor exercise a realistic alternative to surgery in patients with mild degrees of stress incontinence . Also patients with residual symptoms after surgery are c and i date s for pelvic floor training CONTEXT Urinary incontinence is a common condition caused by many factors with several treatment options . OBJECTIVE To compare the effectiveness of biofeedback-assisted behavioral treatment with drug treatment and a placebo control condition for the treatment of urge and mixed urinary incontinence in older community-dwelling women . DESIGN R and omized placebo-controlled trial conducted from 1989 to 1995 . SETTING University-based outpatient geriatric medicine clinic . PATIENTS A volunteer sample of 197 women aged 55 to 92 years with urge urinary incontinence or mixed incontinence with urge as the predominant pattern . Subjects had to have urodynamic evidence of bladder dysfunction , be ambulatory , and not have dementia . INTERVENTION Subjects were r and omized to 4 sessions ( 8 weeks ) of biofeedback-assisted behavioral treatment , drug treatment ( with oxybutynin chloride , possible range of doses , 2.5 mg daily to 5.0 mg 3 times daily ) , or a placebo control condition . MAIN OUTCOME MEASURES Reduction in the frequency of incontinent episodes as determined by bladder diaries , and patients ' perceptions of improvement and their comfort and satisfaction with treatment . RESULTS For all 3 treatment groups , reduction of incontinence was most pronounced early in treatment and progressed more gradually thereafter . Behavioral treatment , which yielded a mean 80.7 % reduction of incontinence episodes , was significantly more effective than drug treatment ( mean 68.5 % reduction ; P=.04 ) and both were more effective than the placebo control condition ( mean 39.4 % reduction ; P<.001 and P=.009 , respectively ) . Patient-perceived improvement was greatest for behavioral treatment ( 74.1 % " much better " vs 50.9 % and 26.9 % for drug treatment and placebo , respectively ) . Only 14.0 % of patients receiving behavioral treatment wanted to change to another treatment vs 75.5 % in each of the other groups . CONCLUSION Behavioral treatment is a safe and effective conservative intervention that should be made more readily available to patients as a first-line treatment for urge and mixed incontinence PURPOSE We determine the efficacy and user acceptability of the urethral occlusive device ( FemAssist ) for incontinence for 1 month and identify factors that may predict successful use of the device . MATERIAL S AND METHODS Baseline and posttreatment outcome measures included a 1-hour pad test , frequency volume chart ( leakage , voiding and number of pads per 24 hour ) , visual analog scale for incontinence impact and quality of life ( Urogenital Distress Inventory ) . The last 36 consecutive women also completed a linear analog scale about attitudes toward touching the genitalia . RESULTS The device was offered to 100 consecutive incontinent women of whom 3 did not enroll in the study and 57 ( 57 % ) completed the 1-month trial . Age , incontinence type or severity and attitudes about touching the genitalia were not significantly different between dropouts and participants . Only 13 % of recruits were disinclined to place the device on the urethra . Significant reduction of incontinence was observed for all outcome measures with the device in situ . Pad testing revealed that 47 % of the patients became continent and 33 % had more than 50 % benefit , while 9 % had worse leakage . Those with severe baseline leakage were equally likely to respond as those with mild or moderate pad test loss . Women with stress , urge or mixed incontinence appeared to respond equally well . CONCLUSIONS The urethral occlusive device provides a further nonsurgical treatment option which is useful for a range of incontinence types In the United Kingdom regular urinary incontinence affects over 2000000 women and costs the NHS about pounds sterling70 million a year on aids and appliances . The assessment and treatment services lack a coherent plan for its recognition and treatment , and where and from whom care is best received is debated.1 Few of the current management strategies ( pelvic exercises , appliances , drugs , and surgery ) have been the subject of well design ed r and omised controlled trials in primary care , and few studies have reported long term results .2 3 4 Thus lack of evidence combined with poorly trained primary care physicians and nurses has meant that fewer than one in three patients are recognised and fewer still are appropriately managed.1 In 1991 we reported the results Sixty-nine female patients with symptoms of stress urinary incontinence were r and omized to treatment with either interferential therapy or weighted vaginal cones . Fifty-four patients completed treatment ( interferential therapy , 30 patients ; weighted vaginal cones , 24 patients ) . Patients were assessed by subjective response , pad testing , continence charts , and the maximum weight of cone that could be held actively and passively . Forty-seven patients were reassessed at 6 months ( 19 cones ; 28 interferential ) , five patients ( 9.26 % ) required surgery , and two patients ( 3.7 % ) could not be reassessed . Subjective response to treatment was good , with 80 % to 90 % of patients cured or improved after treatment . After 6 months , 41.67 % in the cone group and 40 % in the interferential group were subjectively cured , with improvement in 50 % and 30 % , respectively . Of those patients initially referred for treatment , greater than 30 % in each group were cured of symptoms . There was an objective improvement in both groups . In the cone group 50 % had improved after treatment and greater than 60 % had improved at 6 months as assessed by pad testing , while in the interferential group 76 % had improved after treatment and 73 % had improved at 6 months . There was no significant difference in improvement between the two groups in any of the methods of assessment . However , the cones require less supervision by trained staff and can be used at home by the patient . Their use results in a savings in time for the physiotherapy department . The use of the cones is recommended as a cost-effective method of treatment that can be added to the present therapy options available to the physiotherapist The aim of this study was to assess the usefulness of pelvic floor exercises in the treatment of urinary incontinence in women and to analyse the factors which determine a successful outcome . The study involved 66 women who had reported ' genuine stress incontinence ' to their general practitioner . They were assigned at r and om to the treatment or control group . The treatment group received instructions in pelvic floor exercises from a general practitioner . The control group received no therapy . At the start of the trial the severity of the patients ' incontinence was assessed objective ly . This assessment was repeated after three months and patients were also asked for their own perception of whether their incontinence had improved . After the three months ' evaluation the patients in the control group were also given instructions in pelvic floor exercises . After another three months they were assessed in the same way . About 60 % of the patients in the treatment group were dry or mildly incontinent after three months compared with only one patient in the control group ; the mean weekly frequency of incontinence episodes fell from 17 to five in the treatment group but remained virtually unchanged in the control group ; and about 85 % of the women in the treatment group felt that their incontinence had improved or was cured compared with no one in the control group . These results were later corroborated by those for the control group . The most important factor in the success of the treatment was the patients ' motivation , as demonstrated by their adherence to the daily exercises . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract Objective : To compare the effect of pelvic floor exercises , electrical stimulation , vaginal cones , and no treatment for genuine stress incontinence . Design : Stratified , single blind , r and omised controlled trial . Setting : Multicentre . Participants : 107 women with clinical ly and urodynamically proved genuine stress incontinence . Mean ( range ) age was 49.5 ( 24 - 70 ) years , and mean ( range ) duration of symptoms 10.8 ( 1 - 45 ) years . Interventions : Pelvic floor exercise ( n=25 ) comprised 8 - 12 contractions 3 times a day and exercise in groups with skilled physical therapists once a week . The electrical stimulation group ( n=25 ) used vaginal intermittent stimulation with the MS 106 Twin at 50 Hz 30 minutes a day . The vaginal cones group ( n=27 ) used cones for 20 minutes a day . The untreated control group ( n=30 ) was offered the use of a continence guard . Muscle strength was measured by vaginal squeeze pressure once a month . Main outcome measures : Pad test with st and ardised bladder volume , and self report of severity . Results : Improvement in muscle strength was significantly greater ( P=0.03 ) after pelvic floor exercises ( 11.0 cm H2O ( 95 % confidence interval 7.7 to 14.3 ) before v 19.2 cm H2O ( 15.3 to 23.1 ) after ) than either electrical stimulation ( 14.8 cm H2O ( 10.9 to 18.7 ) v 18.6 cm H2O ( 13.3 to 23.9 ) ) or vaginal cones ( 11.8 cm H2O ( 8.5 to 15.1 ) v 15.4 cm H2O ( 11.1 to 19.7 ) ) . Reduction in leakage on pad test was greater in the exercise group ( −30.2 g ; −43.3 to 16.9 ) than in the electrical stimulation group ( −7.4 g ; −20.9 to 6.1 ) and the vaginal cones group ( −14.7 g ; −27.6 to −1.8 ) . On completion of the trial one participant in the control group , 14 in the pelvic floor exercise group , three in the electrical stimulation group , and two in the vaginal cones group no longer considered themselves as having a problem . Conclusion : Training of the pelvic floor muscles is superior to electrical stimulation and vaginal cones in the treatment of genuine stress incontinence OBJECTIVE --To measure the unmet need of patients with regular urinary incontinence ( incontinence twice or more a month ) treatable by a nurse . DESIGN --Self completed postal question naire and r and omised controlled trial of assessment and intervention by a nurse . SETTING --One urban and one rural general practice in Somerset . SUBJECTS--7300 adults r and omly selected from 10,300 aged 35 and over on the combined practice lists . 515 women and 185 men with regular incontinence were offered assessment and treatment , of whom 134 women and 49 men had no intervention for three months ( historical controls ) . They then joined the assessment and treatment programme . INTERVENTION -- Four sessions of pelvic floor exercises and bladder retraining supervised by non-specialist nurse who had taken a three week course on assessing and treating uncomplicated incontinence . MAIN OUTCOME MEASURES --Number of patients desiring treatment ; self reported cure , improvement , or deterioration in continence after three months . RESULTS --The question naire achieved a 79 % response . Vali date d responses showed a prevalence of 4.4 % in men and 16.4 % in women aged 35 - 64 . 315 ( 45 % ) of the 700 patients offered assessment refused it and seven had moved away or died , 64 men and 41 women were referred to their general practitioner . 197 of 292 treated women ( 68 % ) reported cure or improvement compared with seven ( 5 % ) of controls . 22 of the 86 men desiring treatment were suitable for intervention by the nurse . Seventeen were cured or improved compared with none of the men in the control group . CONCLUSIONS --About half the people with regular urinary incontinence took up the offer of treatment ( 9.2 % of women and 3.4 % of men in the study population ) . This condition can be effectively managed by a nurse with limited training Regular urinary incontinence affects one in six adult women . However , for the majority , good continence services are difficult to access and few primary care-based assessment and treatment facilities are available . A large r and omised trial of assessment and treatment in primary care using a trained nurse was conducted in Somerset in 1990 . This report summarises the methods and results of the initial study and reports the four-year follow-up results . The results show that 70 per cent of women will gain long lasting benefit . This model of service provision will also benefit secondary care specialist services by ensuring that patients are appropriately managed in primary care before any possible referral Previous workers have debated the value of maximal perineal stimulation ( MPS ) in the treatment of urinary incontinence in women . In order to assess the efficacy of this simple technique a prospect i ve study was undertaken on 107 consecutive incontinent women . They included those with stress , urge and mixed patterns of leakage . Patients were placed at r and om into treatment and control groups . All underwent clinical assessment , urodynamic study and a single session of pelvic floor re-education with measurement of pelvic contraction and cystoscopy . Those in the treatment group were given MPS using monophasic square wave pulses while under anaesthesia . Independent follow-up assessment was performed 6 and 12 weeks after treatment . Of the 107 patients 94 completed the trial . Forty-five were treated and 49 acted as controls . Analysis of age , parity , duration and severity of incontinence showed that r and omisation had produced comparable results between the treated and the control groups . Sixty per cent of the treatment group and 66 % of the control group had significant symptomatic improvement . Pelvic floor function was re-assessed , using a perineometer , and found to be more efficient , having increased equally in both groups . Both groups of women improved irrespective of the pattern of incontinence . This suggests that MPS does not contribute to the management and that a single physiotherapy session with skillful counselling can produce beneficial results in women with all types of urinary incontinence OBJECTIVES Our purpose was ( 1 ) to evaluate the efficacy on an intent-to-treat basis of a 3-month course of pelvic floor muscle exercises as first-line therapy for urinary incontinence in consecutive women seen in a tertiary care center with stress , urge , and mixed urinary incontinence and ( 2 ) to evaluate whether a specially design ed audiotape improves compliance and efficacy of the exercises . STUDY DESIGN A prospect i ve r and omized trial wa conducted with 71 women seen for treatment of urinary incontinence in two tertiary care center referral clinics ( in the departments of gynecology and urology ) . The primary outcome measure was the number of incontinent episodes , as documented with a 3-day voiding diary . Statistical analysis included t tests and Wilcoxon signed-ranks test , as appropriate . A value of p < or = 0.05 was considered significant . RESULTS Forty-four percent of all enrollees had a > or = 50 % improvement in the number of incontinent episodes per day . This increased to 56 % of enrolles who completed the treatment course . For all enrollees the mean number of incontinent episodes per day decreased from 2.6 to 1.7 for genuine stress incontinence , from 3.5 to 2.3 for detrusor instability , and from 3.9 to 3.2 for mixed incontinence . For enrollees who completed the 3-month course the mean number of incontinent episodes per day decreased from 2.5 to 1.4 for genuine stress incontinence , from 2.8 to 0.5 for detrusor instability , and from 3.0 to 1.7 for mixed incontinence . Six months after completing the course of exercises approximately one third of all enrollees reported that they continued to note good or excellent improvement and desired no further treatment . There was no difference in outcome measures and no difference in compliance between the women who exercised with the aid of the audiotape and those who exercised according to our usual office routine ( p > 0.05 ) . CONCLUSIONS One third of all participants remained improved to the patient 's satisfaction 6 months after completion of a risk-free , inexpensive , simply provided therapy . Our audiotape did not improve our success rate or decrease the dropout rate . In this study the exercises were equally effective for all three urodynamic diagnoses . Inexpensive methods that could be used by primary care providers to improve the success rate of this therapy merits further attention The purpose of this study was to compare the effect of three conservative interventions : pelvic floor muscle training , bladder training , or both , on urodynamic parameters in women with urinary incontinence . Two hundred four women with genuine stress incontinence ( GSI ) or detrusor instability with or without GSI ( DI + /- GSI ) participated in a two-site trial comparing pelvic floor muscle training , bladder training , or both . Patients were stratified based on severity of urinary incontinence , urodynamic diagnosis , and treatment site , then r and omized to a treatment group . All women underwent a comprehensive st and ardized evaluation including multi-channel urodynamics at the initial assessment and at the end of 12 weeks of therapy . Analysis of covariance was used to detect differences among treatment groups on urodynamic parameters . Post-treatment evaluations were available for 181 women . No differences were found among treatments on the following measurements : maximum urethral closure pressure , mean urethral closure pressure , maximum Kegel urethral closure pressure , mean Kegel urethral closure pressure , functional urethral length , pressure transmission ratios , straining urethral axis , first sensation to void , maximum cystometric capacity , and the MCC minus FSV . The effect of treatment did not differ by urodynamic diagnosis . Behavioral therapy had no effect on commonly measured urodynamic parameters . The mechanism by which clinical improvement occurs remains unknown . Neurourol . Urodynam . 18:427 - 436 , 1999 PURPOSE The effectiveness of intravaginal electrical stimulation was compared to st and ard therapy in the treatment of genuine stress urinary incontinence and detrusor instability . MATERIAL S AND METHODS A total of 57 women with urinary incontinence was evaluated with video urodynamics and voiding diaries before and after treatment . Of the women 18 with stress urinary incontinence were r and omized to electrical stimulation or Kegel exercise and 38 with detrusor instability were r and omized to anticholinergic therapy or electrical stimulation . RESULTS Of patients using electrical stimulation in the stress urinary incontinence group 66 % improved and 72 % of the patients with detrusor instability treated with electrical stimulation improved . These rates were not statistically significant when compared to traditional therapy . CONCLUSIONS Electrical stimulation is safe and at least as effective as properly performed Kegel and anticholinergic therapy in the treatment of stress urinary incontinence and detrusor instability OBJECTIVE We compared the efficacy of bladder training , pelvic muscle exercise with biofeedback-assisted instruction , and combination therapy , on urinary incontinence in women . The primary hypothesis was that combination therapy would be the most effective in reducing incontinent episodes . STUDY DESIGN A r and omized clinical trial with three treatment groups was conducted in gynecologic practice s at two university medical centers . Two hundred and four women diagnosed with genuine stress incontinence ( n = 145 ) and /or detrusor instability ( n = 59 ) received a 12-week intervention program ( 6 weekly office visits and 6 weeks of mail/telephone contact ) with immediate and 3-month follow-up . Outcome variables included number of incontinent episodes , quality of life , perceived improvement , and satisfaction . Data analyses consisted of analysis of covariance using baseline values as covariates and chi2 tests . RESULTS The combination therapy group had significantly fewer incontinent episodes , better quality of life , and greater treatment satisfaction immediately after treatment . No differences among groups were observed 3 months later . Women with genuine stress incontinence had greater improvement in life impact , and those with detrusor instability had less symptom distress at the immediate follow-up ; otherwise , no differences were noted by diagnosis , incontinence severity , or treatment site . CONCLUSIONS Combination therapy had the greatest immediate efficacy in the management of female urinary incontinence regardless of urodynamic diagnosis . However , each of the 3 interventions had similar effects 3 months after treatment . Results suggest that the specific treatment may not be as important as having a structured intervention program with education , counseling , and frequent patient contact UNLABELLED We performed a r and omized clinical trial on the efficacy of physical therapy on genuine stress incontinence . STUDY OBJECTIVE " Is a physical therapeutical training program ( pelvic floor muscle training ) combined with biofeedback , more effective than the same program without biofeedback in patients with mild or moderate stress incontinence ? " Forty-four patients were referred by a general practitioner or a urologist . After informed consent , 40 patients were r and omized in an exercises and biofeedback group ( BF ) , or treated with exercises exclusively ( pelvic floor muscle training = PFMT ) . After a diagnostic phase of 1 week every patient received twelve treatment sessions , three times weekly . The primary measure of effect , the quantity of involuntary urine loss , was measured with the 48 hours PAD test ( Inco-test Mölnlycke ) . Before every treatment session the Symptoms question naire was filed out by the patient and the Patient dairy was controlled . The data of the trial were analysed according to the principal of intention to treat . During the trial there was 100 % compliance . There were no drop-outs . Both treatment modalities appeared to be effective . After twelve treatment sessions there was a mean improvement of + /- 55 % ( P = 0.00 ) in both treatment groups , measured by the primary measure of effect . In the group with BF this improvement was already realized after six treatment sessions ( P = 0.01 ) . Yet , the difference between BF and PFMT faded to reach significance at six treatment sessions ( P = 0.08 ) . Although differences in treatment effects between both groups were not significant , our findings suggest that adding biofeedback to pelvic floor muscle exercises might be more effective than pelvic floor muscle exercises alone after six treatments One-third of 450 female soldiers surveyed indicated that they experienced problematic urinary incontinence during exercise and field training activities . The other crucial finding of this survey was probably that 13.3 % of the respondents restricted fluids significantly while participating in field exercises . Although only 5.3 % of respondents felt that their urine leakage had a significant impact on their regular duties , it is obvious that many more are sufficiently worried about leakage to put themselves at significant risk for dehydration-related injuries . This study tested whether behavioral interventions effective among older people could help younger soldiers . Thirty-nine female soldiers reporting exercise-induced urinary incontinence underwent urodynamic assessment s of bladder capacity , urethral closure pressure , and detrusor contraction pressures as well as a symptom question naire before and after therapy . They were stratified by diagnosis of physical stress incontinence or mixed urge/stress incontinence and r and omized into two groups . Twenty-three participants performed pelvic muscle exercises with urethral biofeedback for 8 weeks , and 16 participants performed pelvic muscle exercises alone . Patient reports as well as the post-treatment examinations indicated that all subjects improved significantly . Only five subjects in the biofeedback/exercise and three in the exercise-only group desired further treatment . All subjects initially diagnosed with detrusor dysfunction had normal readings at the end of the study . Thus , behavioral treatments can be effective against exercise-induced urinary incontinence among most female soldiers The purpose of this investigation was to study adherence to exercise , pelvic floor muscle ( PFM ) function and strength and patient satisfaction 5 years after cessation of organized PFM exercise for stress urinary incontinence . All 23 women who had taken part in an " intensive exercise group " in a r and omized trial 5 years ago participated in the follow-up study . Structured interview , vaginal palpation and vaginal squeeze pressure were used to assess the condition , PFM function and muscle strength , respectively . Seventy percent of the women were exercising the PFM once a week or more often . Two women were not able to correctly contract the PFM . Mean PFM strength was 18.1 cm H2O . Three had undergone surgery since the initial study . Sixty-one percent were satisfied with their condition PURPOSE To compare pelvic muscle exercise to pharmacologic treatment of stress urinary incontinence , the most common cause of urine leakage reported by community-living elderly women . SUBJECTS Convenience sample of 157 community-living women , aged 55 to 90 years , after completion of a comprehensive diagnostic evaluation . METHODS Eighty-two subjects were r and omly assigned to the exercise protocol ( with a 34 % attrition rate ) . Pelvic muscle exercises were taught and monitored for 6 months . Phenylpropanolamine hydrochloride was given to the other group in a dose of 50 mg a day , increasing to 50 mg twice a day . MAIN RESULTS Treatment outcomes ( subjective improvement , self recorded frequency of wetting ) were equally satisfactory in both groups . The response to exercises was as good in 5 months as in 6 . It was also as good when the minimum recommended number of exercises per day was 80 as when it was 125 . CONCLUSIONS Among those completing the protocol , pelvic exercises were beneficial in reducing stress incontinence , and the benefit was comparable to that produced by phenylpropanolamine BACKGROUND Urinary incontinence remains a hidden and inadequately treated problem in a high proportion of women . METHODS Ninety women 50 - 74 years of age were recruited to a population -based , r and omized , controlled clinical trial of conservative treatment for urinary incontinence , with delayed treatment for the control group . The study was performed in general practice in three north-Norwegian municipalities , in cooperation with two local departments of gynecology . Three patients were found protocol deviant and analysis was based on 87 patients . INTERVENTION Local estrogen , physiotherapy and electrostimulation combined with close follow-up . MAIN OUTCOME MEASURES 1 . Change in severity of incontinence from start of treatment ( index range 0 - 8 ) . 2 . Change in impact from start of treatment ( index range 0 - 4 ) . 3 . Quantitative measures in relation to micturition . 4 . Criteria based classification into cured , improved , unchanged , worse . RESULTS Treatment reduced severity ( index change 1.8 in the intervention group vs. 0.1 in the control group at six months ) and impact ( index change 0.8 vs. 0.0 ) of leakage . Almost one third of the patients did not complete all micturition tests , but in those who did , average number of wet episodes per 24 hours decreased with treatment , and so did average number of micturitions in urge and mixed incontinence . Forty-nine patients ( 56 % ) were cured or improved after one year . CONCLUSION Women 50 to 74 years of age with urinary incontinence may improve considerably through conservative treatment in general practice Voiding colpo-cysto-urethrography was performed in 52 consecutive female patients with genuine urinary stress incontinence before treatment and in 50 of the patients after treatment . The patients were r and omized to either pelvic floor training or surgery . Surgery included a colposuspension operation in patients with an anterior suspension defect and a vaginal repair in patients with a posterior suspension defect . All pre- and posttreatment examinations were reevaluated blindly by one observer 4 to 6 years later . The pretreatment radiologic reevaluation was in agreement with the original classification in 79 per cent and not in agreement in 21 per cent . Pelvic floor training did not change the degree of suspension defect systematic ally . The effect of squeezing was significantly improved following pelvic floor training . A colposuspension gave rise to a typical radiologic configuration of the bladder and urethra . A vaginal repair was not detectable radiologically and it did not correct a posterior descent . The degree of descent and the degree of incontinence were not correlated and it was not possible radiologically to distinguish treatment failures from treatment success A total of 110 women who had reported urinary incontinence to their general practitioners were r and omly assigned to a treatment or control group . Treatment consisted of pelvic floor exercises in the case of stress incontinence and bladder training in the case of urge incontinence . The results were measured after 3 and 12 months by a research assistant on the basis of a constructed severity scale , an incontinence diary , and a comparison by the patients themselves of their previous and current conditions . After 3 months the control group were given the same treatment . After a further 3 and 12 months , they were assessed in exactly the same way as the treatment group . After 3 months about 60 % of the patients were either dry or only mildly incontinent ; the mean number of wet episodes had gone down from 20 to 7 , and 74 % of the women felt improved or cured . These results were later corroborated by the control group . After 12 months this successful outcome was improved slightly further . It may be concluded that the majority of women with incontinence can be successfully treated by the general practitioner . The effect of this treatment continues after one year OBJECTIVE To compare pelvic floor exercises and vaginal weight cones in the treatment of genuine stress incontinence . STUDY DESIGN R and omised controlled trial . METHODS Sixty ambulatory and fit white women ( mean age 56 years ) with urinary stress incontinence , treated by a single physiotherapist as out patients during twelve weeks . Thirty women were allocated to a weekly session of pelvic floor exercises . Thirty were allocated to using cones , they were seen every two weeks . OUTCOME MEASURES Objective : stress test , vaginal squeezing capacity . Subjective : urinary diary , visual analogue scales . RESULTS Characteristics of both study groups were comparable . Unfortunately , there was an early withdrawal of fourteen ( 47 % ) women in the group treated with cones , and none in the other group . Therefore the pelvic floor exercise group was compared not only with the group intended to be treated with cones , but also with the selected group that only received cone therapy . No statistically significantly differences in outcome measures were found between the groups : 53 % in the group assigned to pelvic floor exercises and 57 % into the group assigned to cones , of which 50 % in the group actually treated with cones , considered themselves as cured or improved to a significant degree . Long-term follow-up was not possible as all cone users refused continued exercises with cones once the twelve weeks had ended . CONCLUSION Pelvic floor exercises and cones are equally effective in the treatment of genuine stress incontinence . Cones are cost and time saving . However , the low patient compliance with the cones importantly limits its clinical applicability , especially in the long run . Therefore , we do not recommend the use of cones BACKGROUND Research using biofeedback as a treatment for sphincteric incontinence began with Kegel 's early studies using a perineometer and pelvic muscle exercises demonstrating a 90 % improvement in urine loss symptoms . More recent studies using varying combinations of biofeedback and pelvic muscle exercises found symptom reduction rates of 78 % to 90 % , but these studies lacked the rigor of a " phase three , " or r and omized controlled clinical trial . METHODS A r and omized controlled trial assessed the efficacy of biofeedback for older women for treatment of sphincteric incompetence . One hundred thirty-five community-dwelling women were r and omized in a single-blind trial to three groups : biofeedback , pelvic muscle exercise , or control . Incontinent episodes were monitored over 8 weeks of treatment and at 3 and 6 months thereafter . RESULTS The number of incontinent episodes decreased significantly in the biofeedback and pelvic muscle exercise subjects but not in the control subjects for all severity of incontinence frequency subgroups . Improvement was maintained within the moderate and severe symptom subgroups for both treatments for at least 6 months but declined in subjects with mild incontinence frequency . Pelvic muscle activity ( EMG ) was significantly correlated with decreases in incontinent episodes , and only the biofeedback subjects showed significant improvement in EMGs . CONCLUSIONS Biofeedback and pelvic muscle exercises are efficacious for sphincteric incompetence in older women . Benefits are maintained and improvement continues for at least 6 months postintervention . These therapies may be useful before considering invasive treatment Pelvic floor muscle exercises are recommended as an initial treatment to women with stress urinary incontinence . This treatment is often unsuccessful because of patient noncompliance . A post-test , experimental control group design was used to examine Pender 's ( 1992 ) concept of an external cue to action , an audiocassette tape , to enhance patient compliance to pelvic floor exercises . Eighty-six women with urodynamically evaluated stress urinary incontinence participated through a Pelvic Floor Exercise Unit at a large teaching hospital . Patients received biofeedback training and written information to reinforce pelvic floor muscle exercises during a 45-min appointment with a nurse . Patients were instructed to perform the exercises for 10 min twice daily . Forty-three women r and omly assigned to an experimental group received an audiocassette tape . Four to 6 weeks later all patients completed a research er-developed question naire that was validity and reliability tested assessing pelvic floor exercise compliance . The 43 patients ( 100 % ) who received the audiocassette tape reported compliance with " routine " exercises . Twenty-two of 34 patients ( 65 % ) who did not receive the tape were compliant ( P = 0.0003 ) . Thirty-four of 41 patients ( 83 % ) who received the tape reported exercise compliance twice a day , while 4 of 34 patients ( 12 % ) in the control group were similarly compliant ( P = 0.0000 ) . The findings suggest adding an audiocassette tape to a pelvic floor exercise program enhances patient compliance for incontinent women compared to verbal and written instruction combined with biofeedback The purpose of this study was to clarify the mechanism by which bladder training affects urinary incontinence . Urodynamic data and specific urodynamic diagnoses of 108 women with urinary incontinence were compared before and 6 months after treatment with bladder training . Before treatment , 76 women had sphincteric incompetence , 11 had detrusor instability , and 16 had both . After treatment , 33 women no longer fulfilled the urodynamic diagnostic criteria for either sphincter or detrusor dysfunction . Controlling for severity before treatment , the number of incontinent episodes post-treatment was not associated with change in urodynamic diagnosis . Only the first sensation to void , voided volume , compliance , functional urethral length , and flow time showed any significant changes between pre- and post-treatment evaluations ; however , none were correlated with change in the number of incontinent episodes . Bladder training does not appear to affect lower tract urodynamic variables or specific urodynamic diagnosis , and it is likely that its mechanism of action reflects adaptive behavioral changes . Physiologic changes not detected with techniques and /or criteria used in this study may still occur & NA ; Nurse practitioners ( NP ) are often confronted with female clients who describe various types of urine loss symptoms . To establish an accurate diagnosis and therapeutic intervention , it is important for the NP to identify the etiology of the urine loss complaint . The purpose of the study is to compare symptoms and physical findings that differentiate between the urodynamic diagnoses of genuine stress incontinence ( GSI ) and mixed incontinence ( MI ) in 135 clinical trial subjects : 123 diagnosed as GSI and 12 as MI . These subjects participated in a r and omized controlled clinical trial to investigate the efficacy of biofeedback and pelvic floor exercises for incontinence treatment . Data were analyzed for significant differences between these two groups on urologic and gynecologic symptoms , pelvic muscle relaxation , vaginal mucosa , vaginal electromyograph readings , urodynamic parameters , and quantified measure of urine loss . One‐way analysis of variance ( ANOVA ) showed significant difference in nocturnal and diurnal voidings and urine loss immediately after sensing the urge to void in the MI and GSI subjects . Chi‐square analyses found a significantly decreased incidence of poor vaginal tone and atrophic vaginal mucosa in the MI group as compared to the GSI group . The MI group also lost significantly more urine than did the GSI group on the h and wash maneuver of the perineal pad test . Although the sample size of MI subjects was small , these results show that a noninvasive history and physical examination can differentiate between urologic diagnoses . This approach provides a cost‐effective expedient protocol to aid the NP in establishing a differential diagnosis between genuine stress and mixed incontinence We aim ed to study the impact of conservative non-pharmacological , non-surgical management on quality of life in elderly incontinent patients . Community-dwelling patients age 60 years or older were r and omized to receive immediate or delayed conservative management . A number of questions relating to quality of life were administered at admission and then at 2 , 4 , 8 and 12 months . By 4 months , incontinence was cured in 25 % and improved in 63 % of patients . The frequency and severity of incontinence was reduced ( p < 0.001 ) , and deferment time was improved ( p < 0.01 ) . There were statistically significant improvements in subjective quality of life measures at 4 and 12 months involving depression ( p < 0.001 ) , isolation ( p < 0.03 ) , embarrassment ( p < 0.001 ) , laundry ( p < 0.001 ) and smell ( p < 0.02 ) when comparing these variables with initial assessment . This effect did not appear to be a placebo effect as evidence d by comparison with the delayed intervention group , and was sustained over 12 months . There are significant short- and long-term benefits to the quality of life of older patients with incontinence when treated by conservative measures . Intervention studies should measure and report quality of life as an outcome variable |
773 | 22,161,378 | Results on criminal activity and incarceration were not possible to be pooled but where the outcome were measured results of single studies do provide evidence that heroin provision can reduce criminal activity and incarceration/imprisonment .
Social functioning improved in all the intervention groups with heroin groups having slightly better results .
If all the studies comparing heroin provision in any conditions vs any other treatment are pooled the direction of effect remain in favour of heroin .
AUTHORS ' CONCLUSIONS The available evidence suggests an added value of heroin prescribed alongside flexible doses of methadone for long-term , treatment refractory , opioid users , to reach a decrease in the use of illicit substances , involvement in criminal activity and incarceration , a possible reduction in mortaliity ; and an increase in retention in treatment . | BACKGROUND Several types of medications have been used for stabilizing heroin users : Methadone , Buprenorphine and levo-alpha-acetyl-methadol ( LAAM . )
The present review focuses on the prescription of heroin to heroin-dependent individuals .
OBJECTIVES To compare heroin maintenance to methadone or other substitution treatments for opioid dependence regarding : efficacy and acceptability , retaining patients in treatment , reducing the use of illicit substances , and improving health and social functioning . | BACKGROUND Heroin-assisted treatment has been found to be effective for people with severe opioid dependence who are not interested in or do poorly on methadone maintenance . AIMS To study heroin-assisted treatment in people on methadone who continue intravenous heroin and in those who are heroin dependent but currently not in treatment . METHOD In an open-label multicentre r and omised controlled trial , 1015 people with heroin dependence received a variable dose of injectable heroin ( n=515 ) or oral methadone ( n=500 ) for 12 months . Two response criteria , improvement of physical and /or mental health and decrease in illicit drug use , were evaluated in an intent-to-treat analysis . RESULTS Retention was higher in the heroin ( 67.2 % ) than in the methadone group ( 40.0 % ) and the heroin group showed a significantly greater response on both primary outcome measures . More serious adverse events were found in the heroin group , and were mainly associated with intravenous use . CONCLUSIONS Heroin-assisted treatment is more effective for people with opioid dependence who continue intravenous heroin while on methadone maintenance or who are not enrolled in treatment . Despite a higher risk , it should be considered for treatment resistance under medical supervision Abstract Objective : To evaluate an experimental heroin maintenance programme . Design : R and omised trial . Setting : Outpatient clinic in Geneva , Switzerl and . Subjects : Heroin addicts recruited from the community who were socially marginalised and in poor health and had failed in at least two previous drug treatments . Intervention : Patients in the experimental programme ( n=27 ) received intravenous heroin and other health and psychosocial services . Control patients ( n=24 ) received any other conventional drug treatment ( usually methadone maintenance ) . Main outcome measures : Self reported drug use , health status ( SF-36 ) , and social functioning . Results : 25 experimental patients completed 6 months in the programme , receiving a median of 480 mg of heroin daily . One experimental subject and 10 control subjects still used street heroin daily at follow up ( difference 44 % ; 95 % confidence interval 16 % to 71 % ) . Health status scores that improved significantly more in experimental subjects were mental health ( 0.58 SD ; 0.07 to 1.10 ) , role limitations due to emotional problems ( 0.95 SD ; 0.11 to 1.79 ) , and social functioning ( 0.65 SD ; 0.03 to 1.26 ) . Experimental subjects also significantly reduced their illegal income and drug expenses and committed fewer drug and property related offences . There were no benefits in terms of work , housing situation , somatic health status , and use of other drugs . Unexpectedly , only nine ( 38 % ) control subjects entered the heroin maintenance programme at follow up . Conclusions : A heroin maintenance programme is a feasible and clinical ly effective treatment for heroin users who fail in conventional drug treatment programmes . Even in this population , however , another attempt at methadone maintenance may be successful and help the patient to stop using injectable opioids The effects of maintenance on a narcotic antagonist , naltrexone ( 50 mg/day p.o . ) , or placebo on patterns of operant acquisition and use of heroin were studied under double-blind conditions . Twelve male heroin addict volunteers lived on a clinical research ward for 34 days . After a 9 day drug-free period , naltrexone or placebo were given and heroin ) 40 mg/day ) was available for 10 days . Subjects could earn money ( $ 1.50 ) or heroin ( 10 mg i.v . ) by responding on a second-order schedule of reinforcement [ FR 300 ( FI 1 sec : S ) ] for approximately 90 min . The three naltrexone-maintained subjects took only 2 to 7.5 % of the total heroin available . Two naltrexone subjects stopped heroin self-administration after the 1st or 2nd heroin injection ; the third subject took a 3rd heroin injection on the 8th day of heroin availability . Naltrexone maintenance for 25 consecutive days did not produce adverse side effects . In contrast , the nine placebo naltrexone subjects used 57.5 to 100 % of the total heroin available . Five placebo subjects used all or all but one of the 40 injections available ; four placebo subjects often used less heroin than was available each day . Heroin intoxication did not impair operant performance . Heroin users worked longer hours and earned more purchase points ( P < .05 ) during heroin self-administration and subsequent methadone detoxification than during the drug-free period . Subjects precisely titrated operant work to acquire the desired amount of heroin , then resumed working for money . These data demonstrate the feasibility of using direct measures of drug self-administration behavior to evaluate new pharmacotherapies for heroin abuse and indicate the effectiveness of naltrexone in suppressing heroin self-administration Abstract Objective To determine whether supervised medical prescription of heroin can successfully treat addicts who do not sufficiently benefit from methadone maintenance treatment . Design Two open label r and omised controlled trials . Setting Methadone maintenance programmes in six cities in the Netherl and s. Participants 549 heroin addicts . Interventions Inhalable heroin ( n = 375 ) or injectable heroin ( n = 174 ) prescribed over 12 months . Heroin ( maximum 1000 mg per day ) plus methadone ( maximum 150 mg per day ) compared with methadone alone ( maximum 150 mg per day ) . Psychosocial treatment was offered throughout . Main outcome measures Dichotomous , multidomain response index , including vali date d indicators of physical health , mental status , and social functioning . Results Adherence was excellent with 12 month outcome data available for 94 % of the r and omised participants . With intention to treat analysis , 12 month treatment with heroin plus methadone was significantly more effective than treatment with methadone alone in the trial of inhalable heroin ( response rate 49.7 % v 26.9 % ; difference 22.8 % , 95 % confidence interval 11.0 % to 34.6 % ) and in the trial of injectable heroin ( 55.5 % v 31.2 % ; difference 24.3 % , 9.6 % to 39.0 % ) . Discontinuation of the coprescribed heroin result ed in a rapid deterioration in 82 % ( 94/115 ) of those who responded to the coprescribed heroin . The incidence of serious adverse events was similar across treatment conditions . Conclusions Supervised coprescription of heroin is feasible , more effective , and probably as safe as methadone alone in reducing the many physical , mental , and social problems of treatment resistant heroin addicts Background The objective of this research was to evaluate data from a r and omized clinical trial that tested injectable diacetylmorphine ( DAM ) and oral methadone ( MMT ) for substitution treatment , using a multi-domain dichotomous index , with a Bayesian approach . Methods Sixty two long-term , socially-excluded heroin injectors , not benefiting from available treatments were r and omized to receive either DAM or MMT for 9 months in Granada , Spain . Completers were 44 and data at the end of the study period was obtained for 50 . Participants were determined to be responders or non responders using a multi-domain outcome index accounting for their physical and mental health and psychosocial integration , used in a previous trial . Data was analyzed with Bayesian methods , using information from a similar study conducted in The Netherl and s to select a priori distributions . On adding the data from the present study to up date the a priori information , the distribution of the difference in response rates were obtained and used to build credibility intervals and relevant probability computations . Results In the experimental group ( n = 27 ) , the rate of responders to treatment was 70.4 % ( 95 % CI 53.2 - 87.6 ) , and in the control group ( n = 23 ) , it was 34.8 % ( 95 % CI 15.3 - 54.3 ) . The probability of success in the experimental group using the a posteriori distributions was higher after a proper sensitivity analysis . Almost the whole distribution of the rates difference ( the one for diacetylmorphine minus methadone ) was located to the right of the zero , indicating the superiority of the experimental treatment . Conclusion The present analysis suggests a clinical superiority of injectable diacetylmorphine compared to oral methadone in the treatment of severely affected heroin injectors not benefiting sufficiently from the available treatments . Trial Registration Current Controlled Trials IS RCT Whilst unsupervised injectable methadone and diamorphine treatment has been part of the British treatment system for decades , the numbers receiving injectable opioid treatment ( IOT ) has been steadily diminishing in recent years . In contrast , there has been a recent expansion of supervised injectable diamorphine programs under trial conditions in a number of European and North American cities , although the evidence regarding the safety , efficacy and cost effectiveness of this treatment approach remains equivocal . Recent British clinical guidance indicates that IOT should be a second-line treatment for those patients in high- quality oral methadone treatment who continue to regularly inject heroin , and that treatment be initiated in newly-developed supervised injecting clinics . The R and omised Injectable Opioid Treatment Trial ( RIOTT ) is a multisite , prospect i ve open-label r and omised controlled trial ( RCT ) examining the role of treatment with injected opioids ( methadone and heroin ) for the management of heroin dependence in patients not responding to conventional substitution treatment . Specifically , the study examines whether efforts should be made to optimise methadone treatment for such patients ( e.g. regular attendance , supervised dosing , high oral doses , access to psychosocial services ) , or whether such patients should be treated with injected methadone or heroin . Eligible patients ( in oral substitution treatment and injecting illicit heroin on a regular basis ) are r and omised to one of three conditions : ( 1 ) optimized oral methadone treatment ( Control group ) ; ( 2 ) injected methadone treatment ; or ( 3 ) injected heroin treatment ( with access to oral methadone doses ) . Subjects are followed up for 6-months , with between-group comparisons on an intention-to-treat basis across a range of outcome measures . The primary outcome is the proportion of patients who discontinue regular illicit heroin use ( operationalised as providing > 50 % urine drug screens negative for markers of illicit heroin in months 4 to 6 ) . Secondary outcomes include measures of other drug use , injecting practice s , health and psychosocial functioning , criminal activity , patient satisfaction and incremental cost effectiveness . The study aims to recruit 150 subjects , with 50 patients per group , and is to be conducted in supervised injecting clinics across Engl and Ninety-six confirmed heroin addicts requesting a heroin maintenance prescription were r and omly allocated to treatment with injectable heroin or oral methadone . Progress was monitored throughout the next 12 months by research workers operating independently of the clinic . Heroin can be seen as maintaining the status quo , with the majority continuing to inject heroin regularly and to supplement their maintenance prescription from other sources ; it was associated with a continuing intermediate level of involvement with the drug subculture and criminal activity . Refusal to prescribe heroin while offering oral methadone constituted a more confrontational response and result ed in a higher abstinence rate , but also a greater dependence on illegal sources of drugs for these who continued to inject . Those offered oral methadone tended to polarize toward high or low categories of illegal drug use and involvement with the drug subculture , and were more likely to be arrested during the 12-month follow-up . There was no difference between the two groups in terms of employment , health , or consumption of nonopiate drugs . Refusal to prescribe heroin result ed in a significantly greater drop out from regular treatment Data from a seven-year follow-up study of heroin addicts were analysed to show group trends . Time spent in various activities was quantified for each person for each year of the follow-up period and used to provide a composite life history . Time spent by the sample using drugs has decreased over the follow-up period . The most marked decrease appeared in the use of heroin , but the analysis suggests that a hard core of heroin users still used heroin several years after coming to the clinic . There seems to be an overall congruence between abstinence and non-clinic attendance . For this sample the use of illegal opiates without attending a clinic was relatively rare , and total time spent in hospitals and in prisons was rather small . Death occurred r and omly during the follow-up period AIMS To investigate whether the neonatal abstinence syndrome ( NAS ) is different in children born to women maintained on slow-release morphine , compared with those maintained on methadone , and to compare additional drug consumption in these groups of women . DESIGN , SETTING AND PARTICIPANTS An open , r and omized trial was conducted in an established clinic . Forty-eight pregnant women who presented to the clinic as opiate or polysubstance abusers were enrolled and maintained on either methadone ( 24 women ) or slow-release morphine ( 24 women ) up to and following delivery . The programme included psychosocial therapy and support for their opiate-addicted partners . MEASUREMENTS St and ard urinalysis methods were used to measure consumption of cocaine and benzodiazepines during pregnancy . Injection sites were monitored to indicate additional opiate use . NAS was measured according to Finnegan score and the amount of phenobarbiturates prescribed to alleviate the symptoms . FINDINGS No difference was found in the number of days that NAS was experienced by neonates born to methadone or morphine maintained mothers ( mean = 16 and 21 days , respectively ) . All children were born healthy and no serious complications arose . Fewer benzodiazepines ( p < 0.05 ) and fewer additional opiates ( p < 0.05 ) were consumed by the morphine-maintained women compared with those who took methadone , but no difference was seen in cocaine consumption . Nicotine consumption was reduced significantly in both groups during pregnancy ( p < 0.02 ) . CONCLUSIONS Both methadone and morphine are suitable maintenance agents for pregnant opiate addicts . Maintenance agents that result in a less prolonged NAS should be studied in further trials AIM This study aim ed to assess the efficacy of the prescription of intravenous diacetylmorphine ( DAM ) versus oral methadone with medical and psychosocial support , with a view of improving physical and mental health as well as social integration among socially excluded , opioid-dependent individuals for whom st and ard treatments have failed . DESIGN This study used an open , r and omized controlled trial . SETTING This study took place in Granada , Spain . PARTICIPANTS Sixty-two opioid-dependent participants were r and omized , 31 in each treatment group , and 50 of them were analyzed . The participants were recruited directly from the streets , through peer outreach , in well-known meeting places for drug-addicted individuals . INTERVENTIONS Participants in the experimental group received injected DAM , twice a day , plus oral methadone , once a day , for 9 months . The control group received only oral methadone , once a day . The two groups received an equivalent opioid dosage . The average DAM dosage was 274.5 mg/day ( range : 15 - 600 mg ) , and an average methadone dosage was 42.6 mg/day ( range : 18 - 124 mg ) . The daily methadone dosage in the control group was 105 mg/day ( range : 40 - 180 mg ) . Comprehensive clinical , psychological , social , and legal support was given to both groups . MEASUREMENTS The following were measured in this study : general health , quality of life , drug-addiction-related problems , nonmedical use of heroin , risk behavior for HIV and HCV , and psychological , family , and social status . FINDINGS Both groups improved with respect to the total domain assessed . Those in the experimental group showed greater improvement in terms of physical health ( the improvement was 2.5 times higher ; p = .034 ) and risk behavior for HIV infection ( the improvement was 1.6 times higher ; p = .012 ) . In addition , this group decreased its street heroin use from 25 days/month to 8 days/month as seen on the Addiction Severity Index ( p = .020 ) , as well as the number of days free from drug-related problems ( the improvement was 2.1 times higher ; p = .004 ) or involvement in crime ( from 11 days/month to < 1 day/month ; p = .096 between groups ) . CONCLUSIONS These findings support the hypothesis that , under the same conditions , DAM could be safely delivered , in our context . Also , in physical health , HIV risk behavior , street heroin use , and days involved in crime , DAM plus methadone was more efficacious than methadone alone . This implies that this treatment could provide an effective alternative for the treatment of socially excluded , opioid-dependent patients with severe physical and mental health problems because of drug addiction , when all available previous treatments have failed AIM To assess the feasibility of a r and omized clinical trial of supervised injectable versus oral methadone maintenance and to assess medium-term treatment outcomes . DESIGN R and omized clinical trial of supervised injectable versus supervised oral methadone maintenance treatment ( MMT ) . Trial participants were dependent illicit opiate injectors allocated at intake to supervised injectable or oral methadone maintenance treatment . SETTING Specialist addictions treatment centre in South London . SUBJECTS Forty dependent illicit opiate injectors seeking methadone maintenance treatment . INTERVENTIONS Daily supervised injectable and oral methadone maintenance , delivered at the treatment centre . MAIN OUTCOME MEASURES Frequency of illicit heroin use and frequency of illicit drug injecting during 30 days before intake to treatment and prior to 6-month follow-up . SECONDARY OUTCOME MEASURES frequency of use of illicit methadone , crack cocaine , benzodiazepines and alcohol , physical and psychological health symptoms and acquisitive crime . RESULTS Injectable and oral MMT were both generally acceptable to the study participants : there was a high level of agreement to enter the r and omized trial , and subsequent retention in treatment was good . The average number of days of illicit heroin use reduced from 22.2 to 7.6 for the injectable MMT group and from 22.4 to 8.7 for the oral MMT group . The average number of days of illicit injecting reduced from 25.7 to 10.8 days for the injectable group and from 20.1 to 11.9 days for the oral group . Patients ' physical and psychological health symptoms and involvement in acquisitive crime also reduced in both groups . Treatment satisfaction ratings at follow-up were higher among patients in the injectable MMT group . The ratio for the actual medication costs between injectable and oral MMT was 6.8:1 , and for the direct operational costs was 4.7:1 . There was some evidence of a differential patient response with greater reductions in heroin use occurring among patients who were daily illicit injectors and had poorer psychological and physical health ( at entry ) who were allocated to injectable MMT . CONCLUSIONS Conduct of the trial has demonstrated that it is feasible to implement supervised injectable methadone maintenance treatment in the context of ( although separate from ) a specialist oral methadone maintenance service . Patients assigned to receive either supervised injectable or oral MMT had broadly equivalent , positive during-treatment outcomes at 6-month follow-up . Future studies should seek to identify patient characteristics which are linked to good outcome in injectable MMT . Practical evidence -based guidance to physicians about determining which patients are more suitable for injectable MMT is urgently needed AIMS To evaluate slow-release oral morphine ( SROM ) as an alternative maintenance pharmacotherapy to methadone for treatment of opioid dependence . DESIGN Open-label crossover study . SETTING Out-patient methadone maintenance programme . PARTICIPANTS Eighteen methadone maintenance patients . Intervention Participants were transferred from methadone to SROM ( once-daily Kapanol trade mark ) for approximately 6 weeks before resuming methadone maintenance . MEASUREMENTS Patient outcomes were assessed ( 1 ) during the transition between medications ( dose requirements , withdrawal severity ) and ( 2 ) after at least 4 weeks on a stable dose of each drug ( treatment preference , patient ratings of treatment efficacy and acceptability , drug use , health , depression and sleep ) . FINDINGS Transfer from methadone to SROM was associated with relatively mild withdrawal for the first 5 days ; the final mean SROM : methadone dose ratio was 4.6 : 1 . Compared to methadone , SROM was associated with improved social functioning , weight loss , fewer and less troublesome side-effects , greater drug liking , reduced heroin craving , an enhanced sense of feeling ' normal ' and similar outcomes for unsanctioned drug use , depression and health . The majority of subjects preferred SROM ( 78 % ) over methadone ( 22 % ) . CONCLUSIONS These findings provide justification for further evaluation of SROM as a maintenance pharmacotherapy for opioid dependence Abstract The purpose of this study is to evaluate the effects of high doses of injected opiates as prescribed maintenance in intravenous drugs users . This was accomplished via a r and omised double-blind study with crossover at an outpatient clinic in Bern , Switzerl and . The subjects were 39 patients with a long history of intravenous opioid use and persistent abuse despite treatment ; they were r and omly allocated to two groups . Group A was started on controlled injection of graduated doses of morphine up to a satisfying individual dose and was then switched as a double blind to heroin at a r and omly determined day between week three and four . Subsequently this group was given heroin for the remaining two to three weeks of the study . Group B was started on heroin and was then switched to morphine in the same manner . Equipotent solutions of 3 % morphine and 2 % heroin were administered . The main outcome measures were clinical observations , structural interviews and self report of subjective experiences to assess the effects of the drugs . In 16 cases , the study had to be discontinued owing to severe morphine-induced histamine reactions . Thirteen participants in Group B presented these adverse reactions on the day of the switch-over . Full data were thus only obtainable for 17 participants . Average daily doses were 491 mg for heroin and 597 mg for morphine . The findings indicate that heroin significantly produced a lower grade of itching , flushing , urticaria and pain/nausea . A negative correlation between dose and euphoria was observed for both heroin and morphine . The authors concluded that as heroin produces fewer side effects it is the preferred highdose maintenance prescription to morphine . The perceived euphoric effects are limited in both substances In the Netherl and s the total number of heroin addicts amounts to approximately 25,000 . Of these about 70 % is in contact with the treatment system . The remaining 30 % have not been seeking help , believes that no help is needed or has lost faith in a better future altogether . Of those who are in treatment , 30 % attempt to stop the use of opiates through participation in drug free abstinence oriented outpatient or inpatient treatment programs . The remaining 70 % have given up the outlook of a drug free existence at least temporarily , and they participate in a methadone maintenance program directed at stabilizing drug use , harm minimization and social integration . In two-thirds these goals are not or only partially achieved . For these patients additional treatment options are needed . Medical prescription of heroin is such an option . However , currently no data are available on the effectiveness of this option . The Dutch study on the effectiveness of medical prescription of heroin is an attempt to obtain these data . In the study , simultaneously two r and omized trials are being executed : one with inhalable and one with injectable heroin . In these trials , 625 ( 375 inhalers and 250 injectors ) chronic treatment-resistant heroin addicts who are currently enrolled in a methadone maintenance program are offered heroin ( in combination with oral methadone ) seven days per week , three times per day for a period of six to twelve months . It is a multi-center study with eight treatment units in six cities in the Netherl and s ( Amsterdam , The Hague , Groningen , Heerlen , Rotterdam , Utrecht ) . At this moment 180 patients have been r and omized . During the treatment no medical complications have been observed and no serious public order or safety problems have occurred . Study participants have been very compliant both with the treatment regimen and the research requirements . The latter is indicated by the fact that 85 % of all the two-monthly assessment s have been completed BACKGROUND Studies in Europe have suggested that injectable diacetylmorphine , the active ingredient in heroin , can be an effective adjunctive treatment for chronic , relapsing opioid dependence . METHODS In an open-label , phase 3 , r and omized , controlled trial in Canada , we compared injectable diacetylmorphine with oral methadone maintenance therapy in patients with opioid dependence that was refractory to treatment . Long-term users of injectable heroin who had not benefited from at least two previous attempts at treatment for addiction ( including at least one methadone treatment ) were r and omly assigned to receive methadone ( 111 patients ) or diacetylmorphine ( 115 patients ) . The primary outcomes , assessed at 12 months , were retention in addiction treatment or drug-free status and a reduction in illicit-drug use or other illegal activity according to the European Addiction Severity Index . RESULTS The primary outcomes were determined in 95.2 % of the participants . On the basis of an intention-to-treat analysis , the rate of retention in addiction treatment in the diacetylmorphine group was 87.8 % , as compared with 54.1 % in the methadone group ( rate ratio for retention , 1.62 ; 95 % confidence interval [ CI ] , 1.35 to 1.95 ; P<0.001 ) . The reduction in rates of illicit-drug use or other illegal activity was 67.0 % in the diacetylmorphine group and 47.7 % in the methadone group ( rate ratio , 1.40 ; 95 % CI , 1.11 to 1.77 ; P=0.004 ) . The most common serious adverse events associated with diacetylmorphine injections were overdoses ( in 10 patients ) and seizures ( in 6 patients ) . CONCLUSIONS Injectable diacetylmorphine was more effective than oral methadone . Because of a risk of overdoses and seizures , diacetylmorphine maintenance therapy should be delivered in setting s where prompt medical intervention is available . ( Clinical Trials.gov number , NCT00175357 . Recently , the Dutch Parliament agreed upon the conduct of a r and omized clinical trial on the effects on heroin provision on general health and psychosocial and criminal behavior in long-term addicts . Previous studies failed to establish the effects beyond reasonable doubt . The main reasons why previous trials failed are massive dropout or noncompliance in the control group . Design ing a new heroin-provision trial , we concluded that the Zelen design provides the best guarantee for obtaining valid study results . Compared with the traditional design , the Zelen design probably reduces noncompliance and dropout considerably , thus increasing validity . Depending on the study population , the Zelen design may reduce study precision . However , in a trial aim ed at badly integrated addicts , the Zelen design can be conducted without loss of precision because baseline measurements will only weakly correlate with effect measurements . The arguments favoring the Zelen design may be generalized to trials in which the experimental treatment is highly attractive to the study participants . However , the use of the Zelen design precludes blinding of participants who receive the experimental treatment . We argue that the conduct of studies that predictably tend to produce invalid results is ethically dubious . The ethical problem of study ing participants without their consent can be solved by a slight modification of the Zelen design in which the sampling of a control group is postponed . Both the traditional and the Zelen design can imply ethical problems . Both design s can be ethically justifiable and should not be rejected on a priori grounds Data from previously reported studies suggest that methadone may be more euphorigenic than other morphine-like drugs . To determine whether methadone is more potent in producing euphoria relative to its other opiate-like effects , single doses of intravenously administered methadone , morphine , heroin and placebo were compared in non-dependent post-addict volunteers . Morphine-like physiologic , subjective and behavioral effects were measured periodically for 24 h after drug administration . Under the conditions of the experiment methadone produced a profile of effects which was indistinguishable from that of morphine and heroin . Only the time course of miosis , which was longer lasting following methadone , differentiated among the three compounds . The relative potencies of methadone , morphine and heroin for the initial 5 h of effect were constant over all opiate-like effects , including measures of euphoria . Thus , methadone was not a selective euphoriant OBJECTIVE To assess the feasibility of offering the choice of prescribing injectable heroin ( diamorphine ) or injectable methadone to opiate-dependent injecting drug users and to assess whether there are health and social gains associated with prescribing injectable opiates . DESIGN A protocol -driven prospect i ve observational study . Type of injectable opiate received was based on self- selection . SETTING A large west London drug clinic . PATIENTS Fifty-eight patients admitted to the clinic between 1 June 1995 and 31 December 1996 , who were long term opiate-dependent injecting drug users , who had previously tried and failed oral methadone and who were apparently unable or unwilling to give up injecting . MAIN OUTCOME MEASURES Retention in treatment , illicit drug use , HIV risk behaviour , criminal activity , social functioning , health and psychological status as measured by self-report , urinalysis and doctor 's ratings . RESULTS Thirty-seven patients ( 64 % ) chose heroin and 21 ( 36 % ) chose injectable methadone . Fifty ( 86 % ) were retained in treatment after three months , 40 ( 69 % ) after six months and 33 ( 57 % ) after 12 months . Among those in treatment at three months , there were significant reductions in illicit drug use , illicit drug-injecting risk behaviour , and criminal activity , and significant improvements in social functioning , health status and psychological adjustment . Generally , these gains were sustained between three , six and 12 months . Doctors ' ratings of health and urinalysis results further supported these findings . CONCLUSIONS Injectable heroin is not always the drug of choice . This intervention retained most patients in treatment with substantial benefits to both patients and the community . Prescribing injectable opiates to long term injecting drug users is a feasible treatment option BACKGROUND Some heroin addicts persistently fail to benefit from conventional treatments . We aim ed to compare the effectiveness of supervised injectable treatment with medicinal heroin ( diamorphine or diacetylmorphine ) or supervised injectable methadone versus optimised oral methadone for chronic heroin addiction . METHODS In this multisite , open-label , r and omised controlled trial , we enrolled chronic heroin addicts who were receiving conventional oral treatment ( > or=6 months ) , but continued to inject street heroin regularly ( > or=50 % of days in preceding 3 months ) . R and omisation by minimisation was used to assign patients to receive supervised injectable methadone , supervised injectable heroin , or optimised oral methadone . Treatment was provided for 26 weeks in three supervised injecting clinics in Engl and . Primary outcome was 50 % or more of negative specimens for street heroin on weekly urinalysis during weeks 14 - 26 . Primary analysis was by intention to treat ; data were adjusted for centre , regular crack use at baseline , and treatment with optimised oral methadone at baseline . Percentages were calculated with Rubin 's rules and were then used to estimate numbers of patients in the multiple imputed sample s. This study is registered , IS RCT N01338071 . FINDINGS Of 301 patients screened , 127 were enrolled and r and omly allocated to receive injectable methadone ( n=42 patients ) , injectable heroin ( n=43 ) , or oral methadone ( n=42 ) ; all patients were included in the primary analysis . At 26 weeks , 80 % ( n=101 ) patients remained in assigned treatment : 81 % ( n=34 ) on injectable methadone , 88 % ( n=38 ) on injectable heroin , and 69 % ( n=29 ) on oral methadone . Patients on injectable heroin were significantly more likely to have achieved the primary outcome ( 72 % [ n=31 ] ) than were those on oral methadone ( 27 % [ n=11 ] , OR 7.42 , 95 % CI 2.69 - 20.46 , p<0.0001 ; adjusted : 66 % [ n=28 ] vs 19 % [ n=8 ] , 8.17 , 2.88 - 23.16 , p<0.0001 ) , with number needed to treat of 2.17 ( 95 % CI 1.60 - 3.97 ) . For injectable methadone ( 39 % [ n=16 ] ; adjusted : 30 % [ n=14 ] ) versus oral methadone , the difference was not significant ( OR 1.74 , 95 % CI 0.66 - 4.60 , p=0.264 ; adjusted : 1.79 , 0.67 - 4.82 , p=0.249 ) . For injectable heroin versus injectable methadone , a significant difference was recorded ( 4.26 , 1.63 - 11.14 , p=0.003 ; adjusted : 4.57 , 1.71 - 12.19 , p=0.002 ) , but the study was not powered for this comparison . Differences were evident within the first 6 weeks of treatment . INTERPRETATION Treatment with supervised injectable heroin leads to significantly lower use of street heroin than does supervised injectable methadone or optimised oral methadone . UK Government proposals should be rolled out to support the positive response that can be achieved with heroin maintenance treatment for previously unresponsive chronic heroin addicts . FUNDING Community Fund ( Big Lottery ) Research section , through Action on Addiction |
774 | 26,999,550 | People with SMI ( particularly MDD ) have a high prevalence of OSA . | BACKGROUND Obstructive sleep apnea ( OSA ) is a health hazard since it is associated with neurocognitive dysfunction and cardio-metabolic diseases .
The prevalence of OSA among people with serious mental illness ( SMI ) is unclear . | The aim of this study was to evaluate prevalence of obstructive sleep apnea among patients undergoing bariatric surgery and the predictive value of various clinical parameters : body mass index ( BMI ) , neck circumference ( NC ) and the Epworth Sleepiness Scale ( ESS ) . We performed a prospect i ve , multidisciplinary , single-center observational study including all patients on the waiting list for bariatric surgery between June 2009 and June 2010 , irrespective of history or clinical findings . Patients visited our ENT outpatient clinic for patient history , ENT and general examination and underwent a full night polysomnography , unless performed previously . As much as 69.9 % of the patients fulfilled the criteria for OSA ( mean BMI 44.2 ± SD 6.4 kg/m2 ) ; 40.4 % of the patients met the criteria for severe OSA . The regression models found BMI to be the best clinical predictor , while the ROC curve found the NC to be the most accurate predictor of the presence of OSA . The discrepancy of the results and the poor statistical power suggest that all three clinical parameters are inadequate predictors of OSA . In conclusion , in this large patient series , 69.9 % of patients undergoing BS meet the criteria for OSA . More than 40 % of these patients have severe OSA . A mere 13.3 % of the patients were diagnosed with OSA before being placed on the waiting list for BS . On statistical analysis , increased neck circumference , BMI and the ESS were found to be insufficient predictors of the presence of OSA . Polysomnography is an essential component of the preoperative workup of patients undergoing BS . When OSA is found , specific perioperative measures are indicated BACKGROUND Limited data have suggested that sleep-disordered breathing , a condition of repeated episodes of apnea and hypopnea during sleep , is prevalent among adults . Data from the Wisconsin Sleep Cohort Study , a longitudinal study of the natural history of cardiopulmonary disorders of sleep , were used to estimate the prevalence of undiagnosed sleep-disordered breathing among adults and address its importance to the public health . METHODS A r and om sample of 602 employed men and women 30 to 60 years old were studied by overnight polysomnography to determine the frequency of episodes of apnea and hypopnea per hour of sleep ( the apnea-hypopnea score ) . We measured the age- and sex-specific prevalence of sleep-disordered breathing in this group using three cutoff points for the apnea-hypopnea score ( > or = 5 , > or = 10 , and > or = 15 ) ; we used logistic regression to investigate risk factors . RESULTS The estimated prevalence of sleep-disordered breathing , defined as an apnea-hypopnea score of 5 or higher , was 9 percent for women and 24 percent for men . We estimated that 2 percent of women and 4 percent of men in the middle-aged work force meet the minimal diagnostic criteria for the sleep apnea syndrome ( an apnea-hypopnea score of 5 or higher and daytime hypersomnolence ) . Male sex and obesity were strongly associated with the presence of sleep-disordered breathing . Habitual snorers , both men and women , tended to have a higher prevalence of apnea-hypopnea scores of 15 or higher . CONCLUSIONS The prevalence of undiagnosed sleep-disordered breathing is high among men and is much higher than previously suspected among women . Undiagnosed sleep-disordered breathing is associated with daytime hypersomnolence CONTEXT Excess body weight is positively associated with sleep-disordered breathing ( SDB ) , a prevalent condition in the US general population . No large study has been conducted of the longitudinal association between SDB and change in weight . OBJECTIVE To measure the independent longitudinal association between weight change and change in SDB severity . DESIGN Population -based , prospect i ve cohort study conducted from July 1989 to January 2000 . SETTING AND PARTICIPANTS Six hundred ninety r and omly selected employed Wisconsin residents ( mean age at baseline , 46 years ; 56 % male ) who were evaluated twice at 4-year intervals for SDB . MAIN OUTCOME MEASURES Percentage change in the apnea-hypopnea index ( AHI ; apnea events + hypopnea events per hour of sleep ) and odds of developing moderate-to-severe SDB ( defined by an AHI > or = 15 events per hour of sleep ) , with respect to change in weight . RESULTS Relative to stable weight , a 10 % weight gain predicted an approximate 32 % ( 95 % confidence interval [ CI ] , 20%-45 % ) increase in the AHI . A 10 % weight loss predicted a 26 % ( 95 % CI , 18%-34 % ) decrease in the AHI . A 10 % increase in weight predicted a 6-fold ( 95 % CI , 2.2 - 17.0 ) increase in the odds of developing moderate-to-severe SDB . CONCLUSIONS Our data indicate that clinical and public health programs that result in even modest weight control are likely to be effective in managing SDB and reducing new occurrence of SDB Daytime sleepiness , impaired cognitive performance and dysphoric mood are often present in patients with obstructive sleep apnoea syndrome ( SAS ) . This prospect i ve controlled study evaluates the effects of treatment with continuous positive airway pressure ( CPAP ) during 1 yr on daytime functioning in a large group of patients with SAS . The authors studied 80 patients ( mean+/-sem 49+/-1 yrs ) with SAS with a mean apnoea-hypopnoea index of 60+/-2 h-1 , and 80 healthy control subjects matched for sex and age ( 46+/-1 yrs . ) . Measurements were obtained at the beginning of the study and 12+/-1 months later , and included : daytime sleepiness ( Epworth scale ) , depression and anxiety ( Beck tests ) , vigilance ( Steer-Clear ) and reaction time ( Psychometer Vigilance Test 192 ) . Drug , coffee and alcohol intake , as well as the sleep schedule , were also recorded . Results showed that , before treatment , patients were more somnolent ( p<0.001 ) , anxious ( p<0.01 ) and depressed ( p<0.001 ) than control subjects . Also , they had a longer reaction time ( p<0.05 ) and poorer vigilance ( p<0.01 ) . The use of CPAP improved significantly the levels of somnolence ( p<0.0001 ) and vigilance ( p<0.01 ) , but failed to modify anxiety and depression . Reaction time changes were minor . Variables with a potential confounding effect did not change during the study . These results provide firm evidence to substantiate the use of continuous positive airway pressure in patients with sleep apnoea syndrome BACKGROUND Results of clinical studies suggest that there may be a relationship between breathing-related sleep disorders and depressive disorders . This study aims to assess the impact of breathing-related sleep disorder on major depressive disorder in the general population . METHOD A cross-sectional telephone survey was carried out between 1994 and 1999 in the general population of the United Kingdom , Germany , Italy , Portugal , and Spain . A total of 18,980 r and omly selected subjects aged 15 to 100 years and representative of the general population of their respective countries participated in the study . The question naire included a series of questions about sleep quality , breathing-related sleep disorder symptoms , mental disorders , and medical conditions . Data are presented using point prevalence . RESULTS 2.1 % of the subjects were found with obstructive sleep apnea syndrome at the time of the interview , and 2.5 % had some other type of DSM-IV breathing-related sleep disorder diagnosis . The association of DSM-IV breathing-related sleep disorder diagnosis and major depressive disorder diagnosis was found in 0.8 % of the sample . As many as 18 % of individuals with a major depressive disorder diagnosis also have a DSM-IV breathing-related sleep disorders diagnosis , and 17.6 % of subjects with a DSM-IV breathing-related sleep disorders diagnosis have a major depressive disorder diagnosis . Multivariate models showed that even after controlling for obesity and hypertension , the odds of having a DSM-IV breathing-related sleep disorders diagnosis was 5.26 for individuals with a major depressive disorder diagnosis . CONCLUSION About 800 of 100,000 individuals have both a breathing-related sleep disorder and a major depressive disorder . The identification of 1 of these 2 disorders should prompt the investigation of the other disorder since nearly a fifth of them have the other disorder |
775 | 29,771,300 | Statistically significant differences in OIRR were found according to tooth type or jaw , inclusion of extraction s , treatment duration , and diagnostic accuracy of the CBCT .
Conclusions Based on the results of this study , CBCT seems to be a reliable tool to examine OIRR during or at the end of orthodontic treatment .
Although the average OIRR measured with CBCT seems to lack clinical relevance , there are certain factors that may affect OIRR following orthodontic treatment . | Background Orthodontically induced external root resorption ( OIRR ) is a pathologic consequence of orthodontic tooth movement .
However , the limitations of two-dimensional radiography suggest that cone beam computed tomography ( CBCT ) with its three-dimensional capabilities might be more suitable to assess OIRR .
Objective The aim of this study was to assess in an evidence -based manner data on linear or volumetric OIRR measurements of permanent teeth by means of CBCT , during and /or after the end of orthodontic treatment . | The aim of this investigation was to compare root resorption in the same individual after application of continuous intrusive and extrusive forces . In nine patients ( mean age 15.3 years ) , the maxillary first premolars were r and omly intruded or extruded with a continuous force of 100 cN for eight weeks . Eleven maxillary first premolars from six r and omly selected orthodontic patients served as controls . Root resorption was determined using scanning electron microscopy . Quantitative assessment of the percentage of resorbed area of the total root surface was performed on composite micrographs . The severity of root resorption was also assessed by visual scoring of the roots . Root resorption mainly occurred at the apical part of the roots in both experimental groups . A significant difference in root resorption was found between the intruded and the control teeth ( P = .006 ) but not between the extruded and the control teeth . However , the mesial and distal root surfaces showed resorption on 5.78 + /- 3.86 % of the root surface of the intruded teeth and 1.28 + /- 1.24 % of the root surface of the extruded teeth , and this difference was significant ( P = .004 ) . In addition , a large individual variation was found . From this study , it can be concluded that intrusion of teeth causes about four times more root resorption than extrusion . Because the amount of root resorption due to intrusion or extrusion in the same patient is correlated , every clinician should be aware that the extrusion of teeth might also cause root resorption in susceptible patients Background Examination with Cone Beam CT ( CBCT ) is common for localizing maxillary canines with eruption disturbance . The benefits and costs of these examinations are unclear . Objectives To measure : 1 . the proportion of orthodontists ' treatment decisions that were different based on intraoral and panoramic radiography ( M1 ) compared with CBCT and panoramic radiography ( M2 ) ; and 2 . the costs of producing different treatment plans , regarding patients with maxillary canines with eruption disturbance . Subjects and methods Orthodontists participated in a web-based survey and were r and omly assigned to denote treatment decisions and the level of confidence in this decision for four patient cases presented with M1 or M2 at two occasions for the same patient case . Results One hundred and twelve orthodontists made 445 assessment s based on M1 and M2 , respectively . Twenty-four per cent of the treatment decisions were different depending on which method the raters had access to , whereof one case differed significantly from all other cases . The mean total cost per examination was € 99.84 using M1 and € 134.37 using M2 , result ing in an incremental cost per examination of € 34.53 for M2 . Limitations Benefits in terms of number of different treatment decisions must be considered as an intermediate outcome for the effectiveness of a diagnostic method and should be interpreted with caution . Conclusions For the patient cases presented in this study , most treatment decisions were the same irrespective of radiological method . Accordingly , this study does not support routine use of CBCT regarding patients with maxillary canine with eruption disturbance OBJECTIVE : To assess the prevalence of severe external root resorption and its potential risk factors result ing from orthodontic treatment . METHODS : A r and omly selected sample was used . It comprised conventional periapical radiographs taken in the same radiology center for maxillary and m and ibular incisors before and after active orthodontic treatment of 129 patients , males and females , treated by means of the St and ard Edgewise technique . Two examiners measured and defined root resorption according to the index proposed by Lev and er et al. The degree of external apical root resorption was registered defining resorption in four degrees of severity . To assess intra and inter-rater reproducibility , kappa coefficient was used . Chi-square test was used to assess the relationship between the amount of root resorption and patient 's sex , dental arch ( maxillary or m and ibular ) , treatment with or without extraction s , treatment duration , root apex stage ( open or closed ) , root shape , as well as overjet and overbite at treatment onset . RESULTS : Maxillary central incisors had the highest percentage of severe root resorption , followed by maxillary lateral incisors and m and ibular lateral incisors . Out of 959 teeth , 28 ( 2.9 % ) presented severe root resorption . The following risk factors were observed : anterior maxillary teeth , overjet greater than or equal to 5 mm at treatment onset , treatment with extraction s , prolonged therapy , and degree of apex formation at treatment onset . CONCLUSION : This study showed that care must be taken in orthodontic treatment involving extraction s , great retraction of maxillary incisors , prolonged therapy , and /or completely formed apex at orthodontic treatment onset OBJECTIVE To evaluate the perception of Greek and Swedish orthodontic practitioners regarding the possible occurrence and prognosis of root resorption occurring during orthodontic treatment and to estimate practitioners ' approaches to the diagnosis of preexisting root resorption , screening of prevalence , and treatment planning approach when moderate or severe root resorption is present . MATERIAL S AND METHODS Question naires were received from r and omly selected Greek ( n = 90 ) and Swedish ( n = 106 ) practitioners . Topics of the questions included ( a ) the presence of history ; ( b ) the radiographic evaluation of root resorption before , during , and after treatment ; ( c ) the treatment approach of initial prevention and protocol s in cases of radiographic diagnosis of root resorption during treatment . RESULTS Of the respondents , 47.1 % of the Swedish practitioners and 32.3 % of the Greek practitioners use periapical and panoramic radiographs to diagnose root resorption , mostly in the anterior region . Both groups recognize trauma , root form , and oral habits as predisposing factors . The majority of Swedish orthodontists perform radiographic follow-up in the first 6 months . In contrast , the Greek orthodontists perform it at 1 year or at the end of treatment . The treatment approach for root resorption that is most frequently used by Swedish orthodontists is altering the treatment plan , using light forces , and allowing resting periods , while the Greek orthodontists most frequently use lighter forces and reduce the total duration of the treatment . CONCLUSIONS Because there is no specific approach offered in the literature , the prevention and treatment re assessment in cases of root resorption relies on individual practitioner perception OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity INTRODUCTION There is still ambiguity about whether continuous or intermittent orthodontic forces produce more root resorption . This prospect i ve r and omized clinical trial was design ed to compare root resorption with these 2 force application patterns . METHODS The sample consisted of 16 maxillary first premolars from 8 patients who required bilateral extraction s as part of their orthodontic treatment . In each subject , a fixed experimental appliance was placed on the maxillary teeth on each side , allowing a buccally directed force . The force was generated by a segmental wire of beta-titanium-molybdenum alloy . The first premolar on 1 side received a buccally directed continuous force , and the contralateral premolar received intermittent force . The initial force magnitude for both sides was 225 cN. After 14 days of initial continuous force , the intermittent force application was obtained with subsequently repeated periods until the end of the eighth week of a 3-day rest period followed by a 4-day force application period . Force levels were set to 225 cN at each patient visit . After the experimental period of 8 weeks , the teeth were extracted under a strict protocol to prevent root surface damage and analyzed with a microcomputed-tomography scan system , and specially design ed software was used for direct volumetric measurements . RESULTS Intermittent force produced less root resorption than continuous force ( P < 0.05 ) . Analysis by position showed that the buccal-cervical region had significantly more root resorption than the other positions ( P < 0.001 ) , corresponding to a region of compression generated by tipping . CONCLUSIONS The application of intermittent orthodontic forces of 225 cN for 8 weeks ( 14 days of force application , 3 days of rest , then 4 days of force application repeated for 6 weeks ) caused less root resorption than continuous forces of 225 cN for 8 weeks . Although it might not be clinical ly practical , compared with continuous forces , intermittent forces might be a safer method to prevent significant root resorption . This regimen , however , could compromise the efficiency of tooth movement Aim : The aim of this prospect i ve study was to radiographically assess root morphology changes in maxillary and m and ibular premolars following Herbst appliance treatment . Patients and Methods : Twenty-five consecutive adolescents ( 19 boys and six girls , mean age 13.08 years ) with Class II , Division 1 malocclusion were treated with the b and ed Herbst appliance for a mean period of 13.16 months . Periapical radiographs of the upper and lower premolars were obtained before appliance insertion and immediately after appliance removal using the parallel technique . All radiographs were scanned , digitized and analyzed using appropriately adjusted cephalometric software . The pre- and post-treatment length and area of the first and second maxillary and m and ibular premolar roots were calculated . Statistical analysis included paired t-tests to evaluate pre- and posttreatment changes , and independent t-tests to compare the pre and post-treatment differences between the first and the second premolars , which served as controls . The level of significance was set at p ≤ 0.05 for all tests . Results : No statistically significant decrease in premolar root lengths or areas was noted following removal of the Herbst appliance . We observed a statistically-significant decrease in the root area of the first m and ibular premolars compared to that of the second m and ibular premolars . Conclusions : Although we observed no statistically-significant root morphology changes in the first and second premolars following Herbst appliance treatment , the m and ibular first premolars revealed significantly more root resorption than did the m and ibular second premolars . ZusammenfassungZiel : Ziel dieser prospektiven Studie war , radiologische Veränderungen der Wurzelmorphologie an Oberkiefer- und Unterkieferprämolaren nach einer Beh and lung mit der Herbst-Apparatur nachzuweisen . Patienten und Method ik:25 aufein and er folgende jugendliche Patienten ( 19 Jungen und sechs Mädchen , mittleres Alter 13,08 Jahre ) mit einer Klasse-II/1-Anomalie wurden i m Schnitt für 13,16 Monate mit einem an Bändern befestigten Herbst-Scharnier beh and elt . Periapikale Röntgenaufnahmen der oberen und unteren Prämolaren wurden vor dem Einsetzen und unmittelbar nach der Entfernung der Apparatur mittels der Paralleltechnik angefertigt . Alle Röntgenaufnahmen wurden eingescannt , digitalisiert und mittels einer adäquat angepassten kephalometrischen Software analysiert . Die Wurzellänge und -fläche der ersten und zweiten Ober- und Unterkieferprämolaren wurden sowohl vor als auch nach der Beh and lung berechnet . Die statistische Analyse enthielt paarige t-Tests zur Evaluation der eingetretenen Veränderungen und unabhängige t-Tests , um diese Veränderungen bei den ersten Prämolaren mit denen der zweiten Prämolaren , die als Kontrollgruppe dienten , zu vergleichen . Das Signifikanz niveau wurde für alle Tests auf p ≤ 0,05 gesetzt . Ergebnisse : Es wurde keine statistisch signifikante Abnahme der Wurzellänge und -fläche der Prämolaren nach Entfernung der Herbst-Apparatur nachgewiesen . Eine statistisch signifikante Abnahme der Wurzelfläche der ersten unteren Prämolaren wurde i m Vergleich zu den zweiten unteren Prämolaren festgestellt . Schlussfolgerungen : Obwohl keine statistisch signifikanten Veränderungen in der Wurzelmorphologie der ersten und zweiten Prämolaren nach Beh and lung mit dem Herbst-Scharnier beobachtet wurden , war eine signifikant erhöhte Wurzelresorption bei den ersten unteren Prämolaren i m Vergleich zu den zweiten unteren Prämolaren offensichtlich OBJECTIVE To compare , through cone-beam computed tomography ( CBCT ) , the root resorption and treatment efficiency of two different mini-implant-assisted modalities in intruding the maxillary incisors . MATERIAL S AND METHODS Thirty-two adults who had deep bite and elongated maxillary incisors were r and omly allocated to two groups : anterior mini-implant group ( AMG ) and posterior mini-implant group ( PMG ) . In the AMG , approximately 40 g of force was applied per side with elastic chains from mini-implants placed between the lateral incisors and canines and in the PMG , with beta-titanium wires from mini-implants placed between the second premolars and first molars . This study was conducted on CBCT scans taken before intrusion and after 4 months of intrusion . Data were analyzed by means of a paired t-test , independent t-test , and Pearson 's correlation test . RESULTS One patient was excluded from the AMG due to mini-implant loosening . While the incisors showed a significant reduction in length and volume , this amount was greater in the AMG , especially in the central incisors ( P < .05 ) . Together with the mean intrusion rates of 0.62 and 0.39 mm/mo in the AMG and PMG respectively , the center of resistance of the incisors showed distal movement with labial tipping ; these changes were greater in the PMG ( P < .001 ) . Volumetric root resorption was correlated with the amount of intrusion ( P < .05 ) . CONCLUSIONS Intrusion anchoring from posterior mini-implants is preferred in cases of upright incisors , as the use of such mechanics directs the roots into the spongiosa where they undergo less root resorption and more labial tipping |
776 | 19,504,035 | Exercise effects appear to be modest , site-specific , and preferentially influence cortical rather than trabecular components of bone .
Exercise type also plays a role , with the most prominent mass and geometric changes being observed in response to high-impact loading exercise .
Exercise appears to positively influence bone mass and geometry in postmenopausal women . | The cumulative risk of fracture for a postmenopausal woman over the age of 50 can reach up to 60 % .
Exercise has the potential to modify fracture risk in postmenopausal women through its effects on bone mass and geometry ; however , these effects are not well characterized . | Summary This study showed that combination of strength , balance , agility and jumping training prevented functional decline and bone fragility in home-dwelling elderly women . The finding supports the idea that it is possible to maintain good physical functioning by multi-component exercise program and thus postpone the age-related functional problems . Introduction This 1-year r and omized , controlled exercise intervention trial assessed the effects of two different training programs and their combination on physical functioning and bone in home-dwelling elderly women . Methods One hundred and forty-nine healthy women aged 70–78 years were r and omly assigned into : group 1—resistance training ( RES ) , group 2—balance-jumping training ( BAL ) , group 3—combination of resistance and balance-jumping training ( COMB ) , and group 4—controls ( CON ) . Self-rated physical functioning , leg extensor force , dynamic balance , and bone mass and structure were measured . Results Self-rated physical functioning improved in the COMB group , but was reduced in the CON group ; the mean inter-group difference was 10 % ( 95 % CI : 0–22 % ) . Mean increase in the leg extensor force was higher in the RES ( 14 % ; 4–25 % ) and COMB ( 13 % ; 3–25 % ) compared with the CON groups . Dynamic balance improved in the BAL ( 6 % ; 1–11 % ) and in the COMB ( 8 % ; 3–12 % ) groups . There were no inter-group differences in BMC at the proximal femur . In those COMB women who trained at least twice a week , the tibial shaft structure weakened 2 % ( 0–4 % ) less than those in the CON group . Conclusions Strength , balance , agility , and jumping training ( especially in combination ) prevented functional decline in home-dwelling elderly women . In addition , positive effects seen in the structure of the loaded tibia indicated that exercise may also play a role in preventing bone fragility Summary This study showed that about a half of the exercise-induced gain in dynamic balance and bone strength was maintained one year after cessation of the supervised high-intensity training of home-dwelling elderly women . However , to maintain exercise-induced gains in lower limb muscle force and physical functioning , continued training seems necessary . Introduction Maintenance of exercise-induced benefits in physical functioning and bone structure was assessed one year after cessation of 12-month r and omized controlled exercise intervention . Methods Originally 149 healthy women 70–78 years of age participated in the 12-month exercise RCT and 120 ( 81 % ) of them completed the follow-up study . Self-rated physical functioning , dynamic balance , leg extensor force , and bone structure were assessed . Results During the intervention , exercise increased dynamic balance by 7 % in the combination resistance and balance-jumping training group ( COMB ) . At the follow-up , a 4 % ( 95 % CI : 1–8 % ) gain compared with the controls was still seen , while the exercise-induced isometric leg extension force and self-rated physical functioning benefits had disappeared . During the intervention , at least twice a week trained COMB subjects obtained a significant 2 % benefit in tibial shaft bone strength index compared to the controls . A half of this benefit seemed to be maintained at the follow-up . Conclusions Exercise-induced benefits in dynamic balance and rigidity in the tibial shaft may partly be maintained one year after cessation of a supervised 12-month multi-component training in initially healthy elderly women . However , to maintain the achieved gains in muscle force and physical functioning , continued training seems necessary UNLABELLED We prospect ively examined vBMD and structural bone parameters assessed by QCT among participants of the InCHIANTI study over a 6-yr follow-up . Periosteal apposition occurred both in men and women . Endocortical resorption causes bone loss in older women despite periosteal apposition . INTRODUCTION To address the hypothesis that age-related changes in BMD and bone geometry may be different in men and women , we prospect ively examined volumetric BMD ( vBMD ) and structural bone parameters assessed by QCT among participants of the InCHIANTI study over a 6-yr follow-up . MATERIAL S AND METHODS Three hundred forty-five men and 464 women 21 - 102 yr of age from the InCHIANTI study , a population -based study in Tuscany , Italy , were included . Tibial QCT bone parameters were measured at enrollment ( 1998 - 2000 ) and at 3- ( 2001 - 2003 ) and 6-yr ( 2004 - 2006 ) follow-ups . RESULTS Periosteal apposition occurred both in men and women . The annual rate of bone periosteal apposition was higher in younger than in older men , whereas in women , the rate of apposition was homogenous across age groups . The age-related medullary expansion , expression of endocortical resorption , was significantly higher in women compared with men . In women , but not in men , accelerated endocortical resorption not sufficiently balanced by periosteal apposition caused accelerated loss in cortical bone mass . The cross-sectional moment of inertia decreased progressively over the life span in both sexes . CONCLUSIONS Endocortical resorption causes bone loss in older women despite periosteal apposition . Obtaining a balance between endocortical resorption and periosteal apposition should be the target for interventions aim ed to decrease bone loss and prevent osteoporosis in older women UNLABELLED The increase in bone fragility after menopause results from reduced periosteal bone formation and increased endocortical resorption . Women with highest remodeling had greatest loss of bone mass and estimated bone strength , whereas those with low remodeling lost less bone and maintained estimated bone strength . INTRODUCTION Bone loss from the inner ( endocortical ) surface contributes to bone fragility , whereas deposition of bone on the outer ( periosteal ) surface is believed to be an adaptive response to maintain resistance to bending . MATERIAL S AND METHODS To test this hypothesis , changes in bone mass and estimated indices of bone geometry and strength of the one-third distal radius , bone turnover markers , and fracture incidence were measured annually in 821 women 30 - 89 years of age for 7.1 + /- 2.5 years . The analyses were made in 151 premenopausal women , 33 perimenopausal women , 279 postmenopausal women , and 72 postmenopausal women receiving hormone replacement therapy ( HRT ) . RESULTS In premenopausal women , periosteal apposition increased the radius width , partly off setting endocortical resorption ; therefore , the estimated cortical thickness decreased . Outward displacement of the thinner cortex maintained bone mass and cortical area and increased estimated bending strength . Estimated endocortical resorption accelerated during perimenopause , whereas periosteal apposition decreased . Further cortical thinning occurred , but estimated bending strength was maintained by modest outward cortical displacement . Endocortical resorption accelerated further during the postmenopausal years , whereas periosteal apposition declined further ; cortices thinned , but because outward displacement was minimal , estimated cortical area and bending strength now decreased . Women with highest remodeling had the greatest loss of bone mass and strength . Women with low remodeling lost less bone and maintained estimated bone strength . In HRT-treated women , loss of bone strength was partly prevented . These structural indices predicted incident fractures ; a 1 SD lower section modulus doubled fracture risk . CONCLUSIONS Periosteal apposition does not increase after menopause to compensate for bone loss ; it decreases . Bone fragility of osteoporosis is a consequence of reduced periosteal bone formation and increased endocortical resorption . Underst and ing the mechanisms of the age-related decline in periosteal apposition will identify new therapeutic targets . On the basis of our results , it may be speculated that the stimulation of periosteal apposition will increase bone width and improve skeletal strength CONTEXT Despite decades of accumulated observational evidence , the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain . OBJECTIVE To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States . DESIGN Estrogen plus progestin component of the Women 's Health Initiative , a r and omized controlled primary prevention trial ( planned duration , 8.5 years ) in which 16608 postmenopausal women aged 50 - 79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993 - 1998 . INTERVENTIONS Participants received conjugated equine estrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOMES MEASURES The primary outcome was coronary heart disease ( CHD ) ( nonfatal myocardial infa rct ion and CHD death ) , with invasive breast cancer as the primary adverse outcome . A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke , pulmonary embolism ( PE ) , endometrial cancer , colorectal cancer , hip fracture , and death due to other causes . RESULTS On May 31 , 2002 , after a mean of 5.2 years of follow-up , the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits . This report includes data on the major clinical outcomes through April 30 , 2002 . Estimated hazard ratios ( HRs ) ( nominal 95 % confidence intervals [ CIs ] ) were as follows : CHD , 1.29 ( 1.02 - 1.63 ) with 286 cases ; breast cancer , 1.26 ( 1.00 - 1.59 ) with 290 cases ; stroke , 1.41 ( 1.07 - 1.85 ) with 212 cases ; PE , 2.13 ( 1.39 - 3.25 ) with 101 cases ; colorectal cancer , 0.63 ( 0.43 - 0.92 ) with 112 cases ; endometrial cancer , 0.83 ( 0.47 - 1.47 ) with 47 cases ; hip fracture , 0.66 ( 0.45 - 0.98 ) with 106 cases ; and death due to other causes , 0.92 ( 0.74 - 1.14 ) with 331 cases . Corresponding HRs ( nominal 95 % CIs ) for composite outcomes were 1.22 ( 1.09 - 1.36 ) for total cardiovascular disease ( arterial and venous disease ) , 1.03 ( 0.90 - 1.17 ) for total cancer , 0.76 ( 0.69 - 0.85 ) for combined fractures , 0.98 ( 0.82 - 1.18 ) for total mortality , and 1.15 ( 1.03 - 1.28 ) for the global index . Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events , 8 more strokes , 8 more PEs , and 8 more invasive breast cancers , while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures . The absolute excess risk of events included in the global index was 19 per 10 000 person-years . CONCLUSIONS Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women . All-cause mortality was not affected during the trial . The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases , and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD Introduction Bone fragility and decreased functional performance are risk factors for osteoporotic fractures . The influence of long-term recreational gymnastics on the maintenance of bone rigidity and physical performance was evaluated . Methods One hundred and seven gymnasts and 110 referents ( 93 % of the original sample ) participated in this 6-year prospect i ve study . Analysis of covariance ( ANCOVA ) was used to estimate the between-group differences and changes by time , and regression analyses to find predictors for changes . Results In both groups agility and leg extensor power decreased by over 3 % and 10 % , respectively , but the original between-group differences , favoring the gymnasts , persisted . Proximal femur bone mineral content ( BMC ) decreased approximately 0.5 % per year in both groups , and femoral neck section modulus decreased . Trabecular density of the distal tibia declined only marginally , and cortical area of the tibial midshaft remained unchanged , while cortical density decreased about 2 % in both groups . After adjustment by age , height , weight , change in weight , and follow-up time , antiresorptive medication and high calcium intake accounted most for the maintenance of bone rigidity . Conclusions In spite of similar rates of decline in bone characteristics and physical performance , the recreational gymnasts ’ overall physical condition was comparable to the level that their less active referents had shown approximately 5 years earlier The separate and combined effects of weight-bearing exercise and hormone replacement therapy ( HRT ) on bone mineral density ( BMD ) were studied in 32 women , 60 to 72 years of age . HRT consisted of continuous conjugated estrogens 0.625 mg/day and trimonthly medroxyprogesterone acetate 5 mg/day for 13 days . Exercise consisted of 2 months of low-intensity exercise followed by 9 months of more vigorous weight-bearing exercise approximately 45 minutes/day , > or = 3 days/week , at 65 - 85 % of maximal heart rate . Lumbar spine and proximal femur BMD were significantly increased in response to exercise and to HRT , and total body BMD was significantly increased in response to HRT ; neither exercise nor HRT had an effect on wrist BMD . The combination of exercise + HRT result ed in increased BMD at all sites except the wrist , with effects being additive for the lumbar spine and Ward 's triangle and synergistic for the total body . Based on reductions in serum osteocalcin levels , it appears that increases in BMD in response to HRT and exercise + HRT were due to decreased bone turnover . The lack of change in serum osteocalcin and IGF-I in response to exercise alone suggests that increases in BMD were due to decreased bone resorption and not increased formation . Results indicate that weight-bearing exercise + HRT may be effective in preventing and /or treating osteoporosis . It is likely that the additive effects of weight-bearing exercise and HRT on bone mineral accretion , coupled with other adaptations to the exercise ( i.e. , increased strength and functional capacity ) , could effectively reduce the incidence of falls and osteoporotic fractures Peak bone mass is an important determinant of bone mass later in life , and an increase in peak bone mass should decrease the risk for osteoporotic fractures [ 1 - 3 ] . Therefore , exact identification of the determinants of peak bone mass could help clinicians devise strategies to prevent fractures . In healthy persons , suggested main determinants of peak bone mass are race , sex , heredity , hormonal status , nutrition , and physical activity [ 4 ] . Of these , genetic factors play a major part , accounting for 60 % to 80 % of the variance [ 1 ] . Still , 20 % to 40 % of the variance may be due to environmental factors , including nutrition and physical activity , and it is important to focus on these factors because both can be easily controlled in generally acceptable ways . The importance of physical activity in maintaining adult bone mass is widely recognized [ 1 , 4 - 6 ] . However , the effects of physical activity on growing bone have received only scant and general attention [ 7 - 10 ] , and , to our knowledge , no prospect i ve , controlled follow-up studies have been done . Cross-sectional studies have provided preliminary evidence of the beneficial effect of exercise on the skeleton during growth , but they left many questions unanswered because of insufficient information about the type , intensity , frequency , and duration of the exercise and because of other limitations in the study design . Therefore , exact determination of the optimal age or level of exercise necessary to achieve maximal peak bone mass has not been possible [ 8 ] . Recent studies have shown unequivocally that bone mass increases dramatically and naturally during puberty and that bone mass reaches its peak before the end of the second decade of life , which is much earlier than was previously thought [ 11 - 15 ] . However , the extent to which physical activity can modify this development and the age at which the effects of exercise are most crucial are unknown . Our objective was to determine the effect of biological age at which unilateral loading was started ( that is , the starting age of training relative to the age at menarche ) on the difference in bone mass in playing and nonplaying arms of female racket-sport players . Using athletes with a known history of unilateral loading and a wide range of starting ages of playing ( from early childhood to early middle age ) , adequately matched nonplaying controls , and a study design with side-to-side comparison , we could control many confounding factors encountered in earlier cross-sectional studies ( intrinsic factors such as age , height , weight , and hormonal status and extrinsic factors such as nutrition , smoking , and alcohol consumption ) . Methods Participants We recruited 105 currently ranked national-level female tennis and squash players for our study through the Finnish tennis and squash federations . The ethical committee for clinical investigation at our institute approved the investigational protocol , and we obtained informed consent from all participants . Ninety-seven players were right-h and ed ( played with the right , dominant h and ) , and the remaining eight were left-h and ed . The mean age of players was 27.7 11.4 years ( SD ) . They were clinical ly healthy with no known diseases and were not receiving medications known to affect bone metabolism ; none had previously had upper extremity fractures . The players ' active training history had to be 5 years or more ( mean , 10 6 years ) . The mean starting age of the playing career ( that is , the age at which the athlete started to practice at least 2 sessions each week on a regular basis ) was 16 9 years . They trained 4.4 times per week on average , and the average duration of each session was 80 minutes ( range , 60 to 180 minutes ) . None of the participants performed or had performed activities , other than playing the racket sport , that affected only one extremity . For the control group , we recruited 50 healthy Finnish women from local schools and work places . All but 2 of them were right-h and ed ( that is , the right h and was dominant ) . The mean age of this group was 27.2 9.2 years . All participants in this group were also clinical ly healthy and had had no previous upper extremity fractures . Although some of them did participate in casual recreational sports ( such as jogging , biking , skiing , swimming , and aerobics ) , none was involved in intense physical training or activities or work affecting the dominant or nondominant arm only . Interview The participants received a mailed question naire , which they completed independently at home . At the session during which anthropometric and strength measurements were obtained , one of three investigators ( PK , HH , or MS ) quickly review ed the question naire responses with participants . This review determined whether the participants had understood and answered all questions . The three procedures ( anthropometric measurements , strength measurements , and question naire review ) were done in r and om order and always after bone measurements were obtained . The investigator was blinded to the bone measurement results . The question naire included data on years of active playing , starting age of playing , number of training sessions per week , training intensity , average duration of each session , physical activities other than tennis or squash playing , injuries , medication , known diseases , diet , possible vitamin or mineral supplementation , consumption of alcohol , and use of cigarettes . We assessed the daily dietary calcium intake using a prospect i ve 7-day question naire on consumed food , and we analyzed the results using Micro-nutrica software ( Social Insurance Institution , Helsinki , Finl and ) . We also asked all participants about the age at onset of menses . We determined the menstrual status and divided the participants into three categories : 1 ) normal cycle of 23 to 35 days , with or without use of low-dose oral contraceptives , 2 ) any irregularity in menstrual pattern [ such as short or long period , anovulatory cycles , short luteal phase , or oligomenorrhea ] , and 3 ) amenorrhea ( no menstruation during the previous 6 months ) . We also asked the participants whether they had ever had disturbances in menstruation and the duration ( in years ) of such disturbances . To test our hypothesis that the biological age at which the playing career was started was important for the development of the side-to-side difference in bone mass , we divided the players into six groups according to the starting age of playing relative to the age at menarche : more than 5 years before menarche , 3 to 5 years before menarche , 2 to 0 years before menarche , 1 to 5 years after menarche , 6 to 15 years after menarche , and more than 15 years after menarche . This division was based on the general knowledge of the pubertal and growth development of healthy Finnish and other white girls [ 11 - 16 ] : Puberty , once begun , is generally complete within 3 years ; growth spurts and accelerated natural bone accumulation begin at the onset of Tanner stage 2 , reach a peak at stages 3 to 4 , and end at stage 5 ; menarche usually occurs during stage 4 ; and the longitudinal growth and natural bone accumulation rates markedly decrease soon after menarche , so that increases are only minimal in Tanner stage 5 . Thus , the women in the six groups could be named as players who had started their playing careers at childhood [ mean starting age , 7.4 1.4 ] years ) prepuberty ( 10.1 1.2 years ) , puberty ( 12.0 1.4 years ) , postpuberty ( 15.2 2.4 years ) , early adulthood ( 24.0 3.0 years ) , and adulthood ( 33.7 3.8 years ) . Anthropometric Measurements We measured the height and weight of each participant . Using a measuring tape , we determined the circumference of upper extremities . We measured upper arm circumference just below the lateral part of the triceps brachii muscle and measured forearm circumference at the middle of the medial epicondyle of the humerus and the styloid process of the ulna . Strength Measurements We determined the maximal isometric strength of upper extremities using an arm flexion-extension dynamometer ( Digitest , Inc. , Muurame , Finl and ) . We measured grip strength using a st and ard grip strength meter . Bone Mineral Measurements Using a Norl and XR-26 DXA scanner ( Norl and , Inc. , Fort Atkinson , Wisconsin ) , a technician determined bone mineral content ( expressed in grams ) from four sites in the upper extremity ( proximal humerus , humeral shaft , radial shaft , and distal radius ) and from the right calcaneus . The same experienced laboratory technician did all measurements . Her day-to-day coefficient of variation for repeated bone mineral content measurements of the same participants was low , ranging from 0.5 % to 1.2 % depending on the site measured [ 17 , 18 ] . Statistical Analyses We made intra-individual side-to-side comparisons using the matched , paired t-test . We used the Student nonpaired t-test to compare the continuous-type background variables , arm and calcaneus bone mineral content , and percentage of side-to-side differences among the players and controls . To compare the noncontinuous background variables of players and controls , we used the chi-square or Fisher exact test . We tested the players ' side-to-side bone mineral content differences across the six groups of players using analysis of variance , analysis of covariance , and a test for linear trend for adjusted group means . According to the previously noted hypothesis that puberty is critical in natural bone accumulation and that menarche is the first sign of cessation of bone development , the analysis of covariance was design ed to include 5 ( 6 1 ) orthogonal or pairwise uncorrelated contrasts : 1 ) starting playing no later than at menarche ( the first three groups ) compared with starting thereafter ( the remaining three groups ) ; 2 ) starting no later than 3 years before menarche ( the first two groups ) compared with starting at menarche ( the third group ) ; 3 ) starting more than 5 years before menarche ( the first group ) compared with starting 3 to 5 years before menarche ( the second group ) ; 4 ) starting 1 It is uncertain whether or how rapidly elderly women continue to lose bone with advancing age . To determine rates of change in bone mass at the hip and at the calcaneus in elderly women and to compare these rates of change among estrogen users and nonusers , we prospect ively measured rates of change in bone mineral density ( BMD ) at the total hip and its four subregions ( mean + /- SD , 3.55 + /- 0.29 years between examinations ) and at the calcaneus ( mean + /- SD , 5.69 + /- 0.33 years between examinations ) in 5689 community-dwelling white women aged 65 years or older at the baseline examination . The rate of decline in total hip BMD steadily increased from 2.5 mg/cm 2/year ( 95 % confidence interval 2.0 to 2.9 ) in women 67 - 69 years old to 10.4 mg/cm 2/year in those aged 85 or older ( 95 % confidence interval 8.4 to 12.4 ) . The rate of bone loss also increased with aging at all subregions of the hip and at the calcaneus . The average loss of bone from the total hip is sufficient to increase the risk of hip fracture by 21 % per 5 years in women aged 80 years or older . Compared with nonusers , current estrogen users had a 33 % lower age-adjusted mean rate of loss at the total hip ( 2.9 vs 4.3 mg/cm 2/year , p < or = 0.0001 ) and a 35 % lower age-adjusted mean rate of loss at the calcaneus ( 3.9 vs 6.0 mg/cm 2/year , p < or = 0.0001 ) . The rate of bone loss in the hip and calcaneus steadily increases with advancing age in older women . Estrogen therapy may significantly decrease this loss . Efforts to underst and and prevent bone loss should include elderly women The effects of a vertical jumping exercise regime on bone mineral density ( BMD ) have been assessed using r and omized controlled trials in both pre- and postmenopausal women , the latter stratified for hormone replacement therapy ( HRT ) . Women were screened for contraindications or medication likely to influence bone . The premenopausal women were at least 12 months postpartum and not lactating ; the postmenopausal women had been stable on , or off , HRT for the previous 12 months and throughout the study . BMD was measured blind using dual-energy X-ray absorptiometry at the spine ( L2-L4 ) and the proximal femur . The exercise consisted of 50 vertical jumps on 6 days/week of mean height 8.5 cm , which produced mean ground reactions of 3.0 times body weight in the young women and 4.0 times in the older women . In the premenopausal women , the exercise result ed in a significant increase of 2.8 % in femoral BMD after 5 months ( p < 0.001 , n = 31 ) . This change was significantly greater ( p < 0.05 ) than that found in the control group ( n = 26 ) . In the postmenopausal women , there was no significant difference between the exercise and control groups after 12 months ( total n = 123 ) nor after 18 months ( total n = 38 ) . HRT status did not affect this outcome , at least up to 12 months . It appears that premenopausal women respond positively to this brief high-impact exercise but postmenopausal women do not A r and omized , controlled , single-blinded 25-wk prospect i ve study was conducted to compare the effects of group-based resistance and agility training on bone , as measured by both dual-energy X-ray absorptiometry ( DXA ) and peripheral quantitative computed tomography ( pQCT ) , in older women with low bone mass . Ninety-eight community-dwelling women aged 75 - 85 yr were r and omized to one of three experimental groups : resistance training ( n = 32 ) , agility training ( n = 34 ) , or stretching ( sham exercise ) ( n = 32 ) . Total hip , femoral neck , and trochanteric bone mineral density ( BMD ) were measured by DXA . Peripheral QCT measurements were performed at the tibia and radius . The pQCT outcome measures at the shaft regions were cortical bone content , cortical bone cross-sectional area , cortical bone density , and density-weighted polar section modulus ( SSI ) . The pQCT outcome measures at the distal sites were total bone content , total bone cross-sectional area , and total bone density . At trial completion , the agility training group significantly increased cortical bone density by 0.5 + /- 0.2 % ( SE ) at the tibial shaft compared with a 0.4 + /- 0.3 % loss in the stretching group . The resistance training group significantly increased cortical bone density ( 1.4 + /- 0.6 % ) at the radial shaft compared , with a 0.4 + /- 0.5 % loss in the agility training group . No significant between-group differences were observed in the other bone outcome measures ( by DXA or pQCT ) . Future research is needed to determine the mechanism(s ) responsible for the observed adaptation of the cortical bone to mechanical loading In this r and omized , double-blind , placebo-controlled 12-month trial we evaluated effects of weight- bearing jumping exercise and oral alendronate , alone or in combination , on the mass and structure of bone , risk factors for falling ( muscle strength and power , postural sway , and dynamic balance ) , and cardiorespiratory fitness in postmenopausal women . A total of 164 healthy , sedentary , early postmenopausal women were r and omly assigned to one of four experimental groups : ( 1 ) 5 mg of alendronate daily plus progressive jumping exercise , ( 2 ) 5 mg alendronate , ( 3 ) placebo plus progressive jumping exercise , or ( 4 ) placebo . The primary endpoint was 12-month change in bone mass and geometry ( measured with dual-energy X-ray absorptiometry and peripheral computed tomography at several axial and limb sites ) and physical performance ; the secondary endpoint was change in biochemical markers of bone turnover . The jumping exercise was conducted an average 1.6 + /- 0.9 ( mean + /- SD ) times a week . Alendronate daily was effective in increasing bone mass at the lumbar spine ( alendronate vs placebo 3.5 % ; 95 % CI , 2.2 - 4.9 % ) and femoral neck ( 1.3 % ; 95 % CI , 0.2 - 2.4 % ) but did not affect other bone sites . Exercise alone had no effect on bone mass at the lumbar spine or femoral neck ; it had neither an additive nor an interactive effect with alendronate at these bone sites . However , at the distal tibia the mean increase of 3.6 % ( 0.3 - 7.1 % ) in the section modulus ( that is , bone strength ) and 3.7 % ( 0.1 - 7.3 % ) increase in the ratio of cortical bone to total bone area were statistically significant in the exercise group compared to the nonexercise group , indicating exercise-induced thickening of the bone cortex . Bone turnover was reduced in alendronate groups only . Alendronate had no effect on physical performance while the jumping exercise improved leg extensor power , dynamic balance , and cardiorespiratory fitness . As conclusion Alendronate is effective in increasing bone mass at the lumbar spine and femoral neck , while exercise is effective in increasing the mechanical properties of bone at some of the most loaded bone sites , as well as improving the participants ' muscular performance and dynamic balance . Together alendronate and exercise may effectively decrease the risk of osteoporotic fractures OBJECTIVE To evaluate the potential benefits of programmed Tai Chi Chun ( TCC ) exercise on the weight-bearing bones of early postmenopausal women . DESIGN Age-matched and r and omized prospect i ve intervention . SETTING University medical school . PARTICIPANTS One hundred thirty-two healthy postmenopausal women ( mean age , 54.0+/-3.5y ) within 10 years of menopause onset were recruited and r and omized into the TCC exercise group ( n=67 ) or the sedentary control group ( n=65 ) . INTERVENTION Supervised TCC exercise was performed by the TCC group for 45 minutes a day , 5 days a week , for 12 months ; control subjects retained a sedentary life style . Main outcome measures Bone mineral density ( BMD ) was measured in the lumbar spine and proximal femur by using dual-energy x-ray absorptiometry and in the distal tibia by using multislice peripheral quantitative computed tomography ( pQCT ) . All BMD measurements were repeated after 12 months in both groups . Fracture rate was also documented . RESULTS Baseline measurements showed homogeneity in age , anthropometric variables , and menstruation status between the TCC and control groups . Exactly 81.6 % of the subjects in the TCC group and 83.1 % of subjects in the control group completed the 12-month follow-up study . BMD measurements revealed a general bone loss in both TCC and sedentary control subjects at all measured skeletal sites , but with a reportedly slower rate in the TCC group . A significant 2.6- to 3.6-fold retardation of bone loss ( P<.01 ) was found in both trabecular and cortical compartments of the distal tibia in the TCC group as compared with the controls , as measured by pQCT . A total of 4 fracture cases were documented during follow-up , including 3 subjects in the control group and 1 in the TCC group . CONCLUSIONS This is the first prospect i ve and r and omized study to show that a programmed TCC exercise intervention is beneficial for retarding bone loss in weight-bearing bones in early postmenopausal women . Long-term follow-up is needed to substantiate the role of TCC exercise in the prevention of osteoporosis and its related fracture Knowledge of the effects of exercise on bone mass in postmenopausal women is limited and controversial . Animal studies have shown that the response of bone to bending strain is an alteration of bone geometry . We studied 250 postmenopausal women , aged 52 - 72 years , willing to participate in a 6-month exercise program . The first 125 started the program immediately and the remaining 125 served as controls . The training program included exercises design ed to maximize the stress on the wrist . One hundred and eighteen of the active group and 116 of the control group completed the study and were reassessed 6 months later . Bone mineral density ( BMD ) of the femoral neck , lumbar spine , ultradistal and proximal radius was measured by dual-energy X-ray absorptiometry ( DXA ) both before and at the end of the exercise program . The forearm was also evaluated by peripheral quantitative computed tomography , which measures the area , bone mineral content ( BMC ) , and volumetric density for both the cortical and the trabecular component . The results showed that the DXA measurements at the femoral neck , lumbar spine , ultradistal and proximal radius were similar between the two groups . No significant difference was detected after the exercise program at the proximal radius . At the ultradistal radius , the cross-sectional area of cortical bone rose by 2.8 + /- 15.0 % ( SD , p < 0.05 ) , apparently for both periosteal apposition and corticalization of the trabecular tissue . The volumetric density of cortical bone rose by 2 . 2 + /- 15.8 % ( p < 0.1 ) , and that of trabecular bone decreased by 2.6 + /- 10.7 % ( p < 0.01 ) . The combined changes in both bone volume and density in the exercise group were associated with marked increase in cortical BMC ( 3.1 + /- 10.7 % , p < 0.01 ) and decrease in trabecular BMC ( -3.4 + /- 14.2 % , p < 0.05 ) , which were statistically different from those observed in the control group ( p < 0.05 ) . In conclusion , these results confirm that site-specific moderate physical exercises have very little effect on bone mass . However , it appears that some exercises may reshape the bone segment under stress by increasing both the cross-sectional area and the density of the cortical component . These structural changes are theoretically associated with increases in the bending strength |
777 | 24,740,584 | Authors ' conclusions Algorithms incorporating RDTs can substantially reduce antimalarial prescribing if health workers adhere to the test results .
Introducing RDTs has not been shown to improve health outcomes for patients , but adherence to the test result does not seem to result in worse clinical outcomes than presumptive treatment .
Concentrating on improving the care of RDT negative patients could improve health outcomes in febrile children | Background In 2010 , the World Health Organization recommended that all patients with suspected malaria are tested for malaria before treatment .
In rural African setting s light microscopy is often unavailable .
Diagnosis has relied on detecting fever , and most people were given antimalarial drugs presumptively .
Rapid diagnostic tests ( RDTs ) provide a point‐of‐care test that may improve management , particularly of people for whom the RDT excludes the diagnosis of malaria .
Objectives To evaluate whether introducing RDTs into algorithms for diagnosing and treating people with fever improves health outcomes , reduces antimalarial prescribing , and is safe , compared to algorithms using clinical diagnosis . | In a cluster r and omized trial , Kojo Yeboah-Antwi and colleagues find that integrated management of malaria and pneumonia in children under five by community health workers is both feasible and effective Objective To test in West Africa the impact of rapid diagnostic tests on the prescription of antimalarials and antibiotics both where microscopy is used for the diagnosis of malaria and in clinical ( peripheral ) setting s that rely on clinical diagnosis . Design R and omised , controlled , open label clinical trial . Setting Four clinics in the rural Dangme West district of southern Ghana , one in which microscopy is used for diagnosis of malaria ( “ microscopy setting ” ) and three where microscopy is not available and diagnosis of malaria is made on the basis of clinical symptoms ( “ clinical setting ” ) . Participants Patients with suspected malaria . Interventions Patients were r and omly assigned to either a rapid diagnostic test or the current diagnostic method at the clinic ( microscopy or clinical diagnosis ) . A blood sample for a research microscopy slide was taken for all patients . Main outcome measures The primary outcome was the prescription of antimalarials to patients of any age whose double read research slide was negative for malaria . The major secondary outcomes were the correct prescription of antimalarials , the impact of test results on antibiotic prescription , and the correct prescription of antimalarials in children under 5 years . Results Of the 9236 patients screened , 3452 were r and omised in the clinical setting and 3811 in the microscopy setting . Follow-up to 28 days was 97.6 % ( 7088/7263 ) . In the microscopy setting , 722 ( 51.6 % ) of the 1400 patients with negative research slides in the rapid diagnostic test arm were treated for malaria compared with 764 ( 55.0 % ) of the 1389 patients in the microscopy arm ( adjusted odds ratio 0.87 , 95 % CI 0.71 to 1.1 ; P=0.16 ) . In the clinical setting , 578 ( 53.9 % ) of the 1072 patients in the rapid diagnostic test arm with negative research slides were treated for malaria compared with 982 ( 90.1 % ) of the 1090 patients with negative slides in the clinical diagnosis arm ( odds ratio 0.12 , 95 % CI 0.04 to 0.38 ; P=0.001 ) . The use of rapid diagnostic tests led to better targeting of antimalarials and antibiotics in the clinical but not the microscopy setting , in both children and adults . There were no deaths in children under 5 years at 28 days follow-up in either arm . Conclusion Where microscopy already exists , introducing rapid diagnostic tests had limited impact on prescriber behaviour . In setting s where microscopy was not available , however , using rapid diagnostic tests led to a significant reduction in the overprescription of antimalarials , without any evidence of clinical harm , and to better targeting of antibiotics . Trial registration Clinical Trials.gov NCT00493922 Background Early diagnosis and prompt , effective treatment of uncomplicated malaria is critical to prevent severe disease , death and malaria transmission . We assessed the impact of rapid malaria diagnostic tests ( RDTs ) by community health workers ( CHWs ) on provision of artemisinin-based combination therapy ( ACT ) and health outcome in fever patients . Methodology /Principal Findings Twenty-two CHWs from five villages in Kibaha District , a high-malaria transmission area in Coast Region , Tanzania , were trained to manage uncomplicated malaria using RDT aided diagnosis or clinical diagnosis ( CD ) only . Each CHW was r and omly assigned to use either RDT or CD the first week and thereafter alternating weekly . Primary outcome was provision of ACT and main secondary outcomes were referral rates and health status by days 3 and 7 . The CHWs enrolled 2930 fever patients during five months of whom 1988 ( 67.8 % ) presented within 24 hours of fever onset . ACT was provided to 775 of 1457 ( 53.2 % ) patients during RDT weeks and to 1422 of 1473 ( 96.5 % ) patients during CD weeks ( Odds Ratio ( OR ) 0.039 , 95 % CI 0.029–0.053 ) . The CHWs adhered to the RDT results in 1411 of 1457 ( 96.8 % , 95 % CI 95.8–97.6 ) patients . More patients were referred on inclusion day during RDT weeks ( 10.0 % ) compared to CD weeks ( 1.6 % ) . Referral during days 1–7 and perceived non-recovery on days 3 and 7 were also more common after RDT aided diagnosis . However , no fatal or severe malaria occurred among 682 patients in the RDT group who were not treated with ACT , supporting the safety of withholding ACT to RDT negative patients . Conclusions / Significance RDTs in the h and s of CHWs may safely improve early and well-targeted ACT treatment in malaria patients at community level in Africa . Trial registration Clinical Trials.gov Objective To compare rapid diagnostic tests ( RDTs ) for malaria with routine microscopy in guiding treatment decisions for febrile patients . Design R and omised trial . Setting Outpatient departments in northeast Tanzania at varying levels of malaria transmission . Participants 2416 patients for whom a malaria test was requested . Intervention Staff received training on rapid diagnostic tests ; patients sent for malaria tests were r and omised to rapid diagnostic test or routine microscopy Main outcome measure Proportion of patients with a negative test prescribed an antimalarial drug . Results Of 7589 outpatient consultations , 2425 ( 32 % ) had a malaria test requested . Of 1204 patients r and omised to microscopy , 1030 ( 86 % ) tested negative for malaria ; 523 ( 51 % ) of these were treated with an antimalarial drug . Of 1193 patients r and omised to rapid diagnostic test , 1005 ( 84 % ) tested negative ; 540 ( 54 % ) of these were treated for malaria ( odds ratio 1.13 , 95 % confidence interval 0.95 to 1.34 ; P=0.18 ) . Children aged under 5 with negative rapid diagnostic tests were more likely to be prescribed an antimalarial drug than were those with negative slides ( P=0.003 ) . Patients with a negative test by any method were more likely to be prescribed an antibiotic ( odds ratio 6.42 , 4.72 to 8.75 ; P<0.001 ) . More than 90 % of prescriptions for antimalarial drugs in low-moderate transmission setting s were for patients for whom a test requested by a clinician was negative for malaria . Conclusions Although many cases of malaria are missed outside the formal sector , within it malaria is massively over-diagnosed . This threatens the sustainability of deployment of artemisinin combination treatment , and treatable bacterial diseases are likely to be missed . Use of rapid diagnostic tests , with basic training for clinical staff , did not in itself lead to any reduction in over-treatment for malaria . Interventions to improve clinicians ' management of febrile illness are essential but will not be easy . Trial registration Clinical trials NCT00146796 Background Presumptive treatment of all febrile patients with anti-malarials leads to massive over-treatment . The aim was to assess the effect of implementing malaria rapid diagnostic tests ( m RDTs ) on prescription of anti-malarials in urban Tanzania . Methods The design was a prospect i ve collection of routine statistics from ledger books and cross-sectional surveys before and after intervention in r and omly selected health facilities ( HF ) in Dar es Salaam , Tanzania . The participants were all clinicians and their patients in the above health facilities . The intervention consisted of training and introduction of m RDTs in all three hospitals and in six HF . Three HF without m RDTs were selected as matched controls . The use of routine m RDT and treatment upon result was advised for all patients complaining of fever , including children under five years of age . The main outcome measures were : ( 1 ) anti-malarial consumption recorded from routine statistics in ledger books of all HF before and after intervention ; ( 2 ) anti-malarial prescription recorded during observed consultations in cross-sectional surveys conducted in all HF before and 18 months after m RDT implementation . Results Based on routine statistics , the amount of artemether-lumefantrine blisters used post-intervention was reduced by 68 % ( 95%CI 57 - 80 ) in intervention and 32 % ( 9 - 54 ) in control HF . For quinine vials , the reduction was 63 % ( 54 - 72 ) in intervention and an increase of 2.49 times ( 1.62 - 3.35 ) in control HF . Before- and -after cross-sectional surveys showed a similar decrease from 75 % to 20 % in the proportion of patients receiving anti-malarial treatment ( Risk ratio 0.23 , 95%CI 0.20 - 0.26 ) . The cluster r and omized analysis showed a considerable difference of anti-malarial prescription between intervention HF ( 22 % ) and control HF ( 60 % ) ( Risk ratio 0.30 , 95%CI 0.14 - 0.70 ) . Adherence to test result was excellent since only 7 % of negative patients received an anti-malarial . However , antibiotic prescription increased from 49 % before to 72 % after intervention ( Risk ratio 1.47 , 95%CI 1.37 - 1.59 ) . Conclusions Programmatic implementation of m RDTs in a moderately endemic area reduced drastically over-treatment with anti-malarials . Properly trained clinicians with adequate support complied with the recommendation of not treating patients with negative results . Implementation of m RDT should be integrated h and -in-h and with training on the management of other causes of fever to prevent irrational use of antibiotics OBJECTIVES To assess if the clinical outcome of patients treated after performing a Rapid Diagnostic Test for malaria ( RDT ) is at least equivalent to that of controls ( treated presumptively without test ) and to determine the impact of the introduction of a malaria RDT on clinical decisions . METHODS R and omized , multi-centre , open clinical trial in two arms in 2006 at the end of the dry and of the rainy season in 10 peripheral health centres in Burkina Faso : one arm with use of RDT before treatment decision , one arm managed clinical ly . Primary endpoint : persistence of fever at day 4 . Secondary endpoints : frequency of malaria treatment and of antibiotic treatment . RESULTS A total of 852 febrile patients were recruited in the dry season and 1317 febrile patients in the rainy season , and r and omized either to be su bmi tted to RDT ( P_RTD ) or to be managed presumptively ( P_CLIN ) . In both seasons , no significant difference was found between the two r and omized groups in the frequency of antimalarial treatment , nor of antibiotic prescription . In the dry season , 80.8 % and 79.8 % of patients with a negative RDT were nevertheless diagnosed and treated for malaria , and so were 85.0 % and 82.6 % negative patients in the rainy season . In the rainy season only , both diagnosis and treatment of other conditions were significantly less frequent in RDT positive vs. negative patients ( 48.3 % vs. 61.4 % and 46.2 % vs. 59.9 % , P = 0.00 and 0.00 , respectively ) . CONCLUSION Our study was inconclusive on RDT safety ( clinical outcome in the two r and omized groups ) , because of an exceedingly and unexpectedly low compliance with the negative test result . Further research is needed on best strategies to promote adherence and on the safety of a test based strategy compared with the current , presumptive treatment strategy Shortly after Kenya introduced artemether-lumefantrine ( AL ) for first-line treatment of uncomplicated malaria , we conducted a pre-post cluster r and omized controlled trial to assess the effect of providing malaria rapid diagnostic tests ( RDTs ) on recommended treatment ( patients with malaria prescribed AL ) and overtreatment ( patients without malaria prescribed AL ) in out patients > /= 5 years old . Sixty health facilities were r and omized to receive either RDTs plus training , guidelines , and supervision ( TGS ) or TGS alone . Of 1,540 patients included in the analysis , 7 % had uncomplicated malaria . The provision of RDTs coupled with TGS emphasizing AL use only after laboratory confirmation of malaria reduced recommended treatment by 63%-points ( P = 0.04 ) , because diagnostic test use did not change ( -2%-points ) , but health workers significantly reduced presumptive treatment with AL for patients with a clinical diagnosis of malaria who did not undergo testing ( -36%-points ; P = 0.03 ) . Health workers generally adhered to RDT results when prescribing AL : 88 % of RDT-positive and 9 % of RDT-negative patients were treated with AL , respectively . Overtreatment was low in both arms and was not significantly reduced by the provision of RDTs ( -12%-points , P = 0.30 ) . RDTs could potentially improve malaria case management , but we urgently need to develop more effective strategies for implementing guidelines before large scale implementation |
778 | 30,340,498 | Self-monitoring interventions and individual lifestyle counselling led to , or were associated with reduced meat consumption .
Providing information about the health or environmental consequences of eating meat was associated with reduced intentions to consume and select meat in virtual environments , but there was no evidence to suggest this approach influenced actual behaviour .
Education about the animal welfare consequences of eating meat was associated with reduced intentions to consume meat , while interventions implicitly highlighting animal suffering were not .
Education on multiple consequences of eating meat led to mixed results .
Tailored education was not found to reduce actual or intended meat consumption , though few studies assessed this approach .
ConclusionS ome interventions targeting conscious determinants of human behaviour have the potential to reduce the dem and for meat .
In particular , self-monitoring interventions and individual lifestyle counselling can help to reduce meat consumption .
There was evidence of effectiveness of some educational messages in reducing intended consumption and selection of meat in virtual environments . | Background Reducing meat consumption can help prevent non-communicable diseases and protect the environment .
Interventions targeting conscious determinants of human behaviour are generally acceptable approaches to promote dietary change , but little is known about their effectiveness to reduce the dem and for meat .
Objective To evaluate the effectiveness of interventions targeting conscious determinants of human behaviour to reduce the dem and for meat . | The present study aim ed to extend the literature on text messaging interventions involved in promoting healthy eating behaviours . The theoretical framework was the Theory of Planned Behaviour ( TPB ) . A r and omized controlled trial was used to test the impact of daily text messages compared to no message ( groups ) for reducing processed meat consumption ( PMC ) over a 2 week period , testing the sequential mediation role of anticipated regret and intention on the relationship between groups and PMC reduction . PMC and TPB variables were assessed both at Time 1 and Time 2 . Participants were Italian undergraduates ( at Time 1 N = 124 ) r and omly allocated to control and message condition groups . Undergraduates in the message condition group received a daily SMS , which focused on anticipated regret and urged them to self-monitor PMC . Participants in the control group did not receive any message . Those who completed all measures at both time points were included in the analyses ( N = 112 ) . Findings showed that a daily messaging intervention , controlling for participants ' past behaviour , reduced self-reported consumption of PMC . Mediation analyses indicated partial serial mediation via anticipated regret and intentions . The current study provided support for the efficacy of a daily messaging intervention targeting anticipated regret and encouraging self-monitoring in decreasing PMC . Outcomes showed the important mediating role of anticipated regret and intentions for reducing PMC RATIONALE The present studies aim ed to contribute to the literature on psychological variables involved in reducing red meat consumption ( RMC ) . OBJECTIVE Study 1 investigated whether the theory of planned behaviour ( TPB ) , plus healthy-eating and meat-eating identities , could explain intentions to reduce RMC . Study 2 evaluated the effectiveness of an SMS text message intervention on self-monitoring to reduce RMC . METHODS In Study 1 , data were collected daily using online food diaries for one week and a TPB question naire . Study 2 was a r and omised controlled trial assessing pre- and post-RMC and TPB constructs by online food diaries and question naires over a one-week period . Participants were Italian undergraduates in each study ( Study 1 : N = 405 ; Study 2 : N = 244 ) . In Study 2 , participants were r and omly allocated to control and message condition groups . Participants in the message condition group received a daily SMS , which reminded them to monitor RMC , while participants in the control group did not receive any message . Only students who completed all measures were considered in the analyses ( Study 1 : N = 342 ; Study 2 : N = 228 ) . RESULTS Study 1 showed that affective and instrumental attitudes , perceived behavioural control , and meat-eating identity explained intentions to reduce RMC , while subjective norm , past behaviour , and healthy-eating identity did not . Study 2 showed that an SMS intervention was effective in increasing intentions and reducing RMC . Mediation analyses indicated partial serial mediation through healthy-eating and meat-eating identities and intentions . CONCLUSION The present studies provide support for the predictive validity of TPB in explaining intentions to reduce RMC and for the efficacy of an SMS intervention targeting self-monitoring in reducing RMC . Findings confirmed the important role of eating identities in explaining intentions to reduce RMC and in changing this behaviour Disease risk factors identified in epidemiological studies serve as important public health tools , helping clinicians identify individuals who may benefit from more aggressive screening or risk-modification procedures , allowing policymakers to prioritize intervention programs , and encouraging at-risk individuals to modify behavior and improve their health . These factors have been based primarily on evidence from cross-sectional and prospect i ve studies , as most do not lend themselves to r and omized trials . While some risk factors are not modifiable , eating habits are subject to change through both individual action and broader policy initiatives . Meat consumption has been frequently investigated as a variable associated with diabetes risk , but it has not yet been described as a diabetes risk factor . In this article , we evaluate the evidence supporting the use of meat consumption as a clinical ly useful risk factor for type 2 diabetes , based on studies evaluating the risks associated with meat consumption as a categorical dietary characteristic ( i.e. , meat consumption versus no meat consumption ) , as a scalar variable ( i.e. , gradations of meat consumption ) , or as part of a broader dietary pattern With growing awareness that sustainable consumption is important for quality of life on earth , many individuals intend to act more sustainably . In this regard , interest in reducing meat consumption is on the rise . However , people often do not translate intentions into actual behavior change . To address this intention-behavior gap , we tested the self-regulation strategy of mental contrasting with implementation intentions ( MCII ) . Here , people identify and imagine a desired future and current obstacles st and ing in its way . They address the obstacles with if-then plans specifying when , where , and how to act differently . In a 5-week r and omized controlled experimental study , we compared an information + MCII intervention with an information-only control intervention . As hypothesized , only MCII participants ’ intention of reducing their meat consumption was predictive of their actual reduction , while no correspondence between intention and behavior change was found for control participants . Participants with a moderate to strong intention to reduce their meat consumption reduced it more in the MCII than in the control condition . Thus , MCII helped to narrow the intention-behavior gap and supported behavior change for those holding moderate and strong respective intentions Background Swaps are often used to encourage healthier food choices , but there is little evidence of their effectiveness . The current study assessed the impact of offering swaps on groceries purchased within a bespoke online supermarket ; specifically the objective was to measure the impact on energy density ( ED ) of food purchases following the offer of lower ED alternatives ( a ) at point of selection or at checkout , and ( b ) with or without explicit consent to receive swap prompts . Method Participants were asked to complete a 12-item shopping task within an online shopping platform , developed for study ing food purchasing . 1610 adults were r and omly assigned to a no swap control condition or to one of four interventions : consented swaps at selection ; consented swaps at checkout ; imposed swaps at selection ; or imposed swaps at checkout . Each swap presented two lower ED options from the same category as the participant ’s chosen food . Swap acceptance rate and purchased food ED were the primary outcomes . Results Of the mean 12.36 ( SD 1.26 ) foods purchased , intervention participants were offered a mean of 4.1 ( SD 1.68 ) swaps , with the potential to reduce the ED of purchased food ( effect ( 95 % CI ) : −83 kJ/100 g ( −110 – -56 ) , p = < 0.0001 ) . A median of one swap ( IQR 0 to 2 ) was accepted , not significantly reducing the purchased food ED ( effect ( 95 % CI ) : −24 kJ/100 g ( 4 – -52 ) , p = 0.094 ) . More swaps were accepted when offered at selection than at checkout ( OR ( 95 % CI ) = 1.224 ( 1.11 – 1.35 ) , p < 0.0001 ) , but no differences were seen with consent . Purchased food ED was unaffected by point of swap or consent , but reduced with number of swaps accepted ( effect per swap ( 95 % CI ) = −24 kJ/100 g ( −35 – -14 ) , p < 0.0001 ) . Conclusion Within category swaps did not reduce the ED of food purchases reflecting the observation that the use of swaps within an on-line shopping platform offered small potential gains in ED and a minority was accepted OBJECTIVE To investigate the feasibility and short-term effectiveness of a lifestyle intervention for colorectal cancer ( CRC ) survivors . METHODS CanChange was telephone-delivered to 20 CRC survivors by health coaches over 6 weeks supported by an interactive participant h and book . We assessed program feasibility ( program retention and satisfaction ) and health outcomes [ CRC-specific symptoms ( fatigue , nausea , diarrhoea ) , quality of life ( QOL ) , and lifestyle variables ( physical activity , dietary intake , alcohol intake , smoking , body mass index ( BMI ) ) ] at baseline and post-intervention . RESULTS Post-intervention , 76 % of participants rated the program as excellent , 100 % rated the health coach as excellent , and 75 % rated the h and book as excellent . In addition , 80 % said that CanChange addressed their issues , 72 % said that CanChange helped them deal more effectively with their problems , and 100 % said that CanChange made them more motivated to make positive life changes . Finally , all participants said that they would recommend CanChange to other CRC survivors . From baseline to post-intervention we observed : non-significant improvements in all CRC-specific symptoms and QOL ; a significant decrease in processed meat intake [ median ( interquartile range ) : 1.0 ( 3.0 ) vs 0.0 ( 1.0 ) , p=0.01 ] ; as well as non-significant improvements in sedentary behaviour , and the proportion of participants meeting the national guidelines for fruit and vegetable intake . We observed no change in smoking status , while the results for alcohol intake , physical activity , and BMI were variable . CONCLUSIONS CanChange was a feasible and potentially effective lifestyle intervention to improve health outcomes for CRC survivors . A large r and omised controlled trial will follow to test the longer-term effects of this approach Background : This report examines the outcome data for Project PREVENT , a two-site r and omized control trial design ed to reduce behavioral risk factors for colorectal cancer among individuals who have been diagnosed with adenomatous colon polyps . Methods : The study sample included 1,247 patients with recent diagnosis of adenomatous colorectal polyps . Within 4 weeks following the polypectomy , participants completed a baseline survey by telephone , and were r and omized to either Usual Care ( UC ) or the PREVENT intervention , which was design ed to target multiple risk factors . The intervention consisted of a telephone-delivered intervention plus tailored material s , and focused on the six primary behavioral risk factors for colorectal cancer , including red meat consumption , fruit and vegetable intake , multivitamin intake , alcohol , smoking , and physical inactivity . Results : Participation in the PREVENT intervention was associated with a significantly greater reduction in prevalence of multiple risk factors for colorectal cancer compared with UC . Only about one third of UC participants dropped any risk factors during the study period , compared with almost half of the PREVENT participants . PREVENT participants were also significantly more likely to change more than one behavior than UC participants . Conclusions : The PREVENT intervention was effective in helping patients change multiple risk factors . These results provide further support that more comprehensive interventions that move beyond emphasis on a single risk factor are acceptable to patient population s , can result in improvements , and are cost effective OBJECTIVES We analyzed outcomes from a study that examined social- context ual factors in cancer prevention interventions for working class , multiethnic population s. METHODS Ten community health centers were r and omized to intervention or to control . Patients who resided in low-income , multiethnic neighborhoods were eligible ; the intervention targeted fruit and vegetable consumption , red meat consumption , multivitamin intake , and physical activity . Outcomes were measured at 8 months . RESULTS The intervention led to significant increases in fruit and vegetable consumption and multivitamin intake and reductions in red meat consumption ; no change was found in physical activity levels . The intervention effect was not changed when context ual variables that may function as confounders or effect modifiers ( e.g. , gender , education , race/ethnicity , respondent and parents ' country of birth , and poverty status ) were included in the analyses . CONCLUSIONS The intervention led to significant improvements in health behaviors among a working class , multiethnic population , regardless of race/ ethnicity and socioeconomic status . Interventions that respond to the social context of working class individuals across racial/ethnic categories hold promise for improving cancer-related risk behaviors BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application OBJECTIVES To assess the effect of a nutrition education intervention on nutritional factors and oxidative stress during treatment of breast cancer . DESIGN Nonr and omized clinical trial conducted in 2010 - 2011 , including an evaluation at baseline and after 12 months . PARTICIPANTS Women from Brazil who had breast cancer , divided into an intervention group ( IG ) ( n = 18 ) and comparison group ( n = 75 ) . INTERVENTION To increase intake of fruits and vegetables and reduce red and processed meats , via telephone and printed material s. MAIN OUTCOME MEASURES Food intake , anthropometry , and levels of lipid hydroperoxide , carbonyl proteins , reduced glutathione , and ferric reducing antioxidant power . ANALYSES Chi-square , Mann-Whitney or t tests for baseline data ; Wilcoxon or paired t tests for intra-group outcomes , linear regression models , and Bonferroni multiplicity adjustment . RESULTS The research ers observed an increase in fruit and vegetable intake , reduction in red and processed meat intake , no change in body weight , and an increase in glutathione in the IG over the comparison group . However , after Bonferroni adjustment , only the consumption of fruits and vegetables and fruit was significantly higher in IG . CONCLUSIONS AND IMPLICATION S This study presents improved dietary changes after a theory-driven nutrition education intervention . Although the sample size is small , it has proven to be clinical ly relevant ABSTRACT Background Diet is an important determinant of health , and food purchasing is a key antecedent to consumption . Objective We set out to evaluate the effectiveness of grocery store interventions to change food purchasing , and to examine whether effectiveness varied based on intervention components , setting , or socioeconomic status . Design We conducted a systematic review of r and omized controlled trials ( search performed June 2017 ) . Studies must have : aim ed to change food purchasing ; been implemented in grocery stores ( real or simulated ) ; reported purchasing ; and had a minimal control or compared interventions fulfilling our criteria . Search ing , screening , bias assessment , and data extraction followed Cochrane methods . We grouped studies by intervention type ( economic , environmental , swaps , and /or education ) , synthesized results narratively , and conducted an exploratory qualitative comparative analysis . Results We included 35 studies representing 89 interventions , > 20,000 participants , and > 800 stores . Risk of bias was mixed . Economic interventions showed the most promise , with 8 of the 9 studies in real stores and all 6 in simulated environments detecting an effect on purchasing . Swap interventions appeared promising in the 2 studies based in real stores . Store environment interventions showed mixed effects . Education-only interventions appeared effective in simulated environments but not in real stores . Available data suggested that effects of economic interventions did not differ by socioeconomic status , whereas for other interventions impact was variable . In our qualitative comparative analysis , economic interventions ( regardless of setting ) and environmental and swap interventions in real stores were associated with statistically significant changes in purchasing in the desired direction for ≥1 of the foods targeted by the intervention , whereas education-only interventions in real stores were not . Conclusions Findings suggest that interventions implemented in grocery stores — particularly ones that manipulate price , suggest swaps , and perhaps manipulate item availability — have an impact on purchasing and could play a role in public health strategies to improve health . Review protocol registered at https://www.crd.york.ac.uk/ PROSPERO / as CRD42017068809 Summary Background Reducing meat consumption could help to protect the natural environment and promote population health . Interventions restructuring physical micro-environments might help to change habitual behaviour . We synthesis ed the scientific evidence pertaining to whether , and which , interventions restructuring physical micro-environments effectively reduce the dem and for meat . Methods We did a systematic review of quantitative studies evaluating the effectiveness of interventions restructuring physical micro-environments to reduce the dem and for meat . We identified relevant records by search ing six electronic data bases ( CAB Abstract s , Embase , PsycINFO , Science Citation Index , MEDLINE , and Dissertations & Theses ) on Aug 31 , 2017 , contacting experts , screening publicly accessible online re sources , and search ing references . We included studies that evaluated the effectiveness of interventions restructuring physical micro-environments to reduce the dem and for meat , defined as the actual or intended consumption , purchase , or selection of meat in real or virtual environments . We extracted data pertaining to the study sample s , the interventions , and meat dem and at the follow-up closest to intervention completion and at the longest follow-up , with the former representing our primary outcome . We synthesis ed data narratively and did a qualitative comparative analysis to identify configurations of intervention characteristics associated with , and those not found to be associated with , significant reductions in meat dem and . Our Systematic Review is registered with PROSPERO , number CRD42017081532 . Results Of 10 733 titles and abstract s screened for eligibility , we assessed 60 full papers and included 14 papers reporting on 18 studies with 22 intervention conditions . Three interventions reducing the portion size of meat servings reduced meat consumption in r and omised trials . Three interventions providing meat alternatives with supporting educational material were associated with reduced meat dem and in pre-post design studies . Three of four interventions altering the sensory properties ( eg , visual presentation ) of meat or meat alternatives at point of purchase reduced meat dem and in r and omised trials . Four interventions repositioning meat products to be less prominent at point of purchase were associated with lower meat dem and , but only two such interventions reached statistical significance in a r and omised trial and a multiple treatment reversal design . Only one of five interventions manipulating the description of meat or meat alternatives at point of purchase was associated with lower meat dem and in a multiple treatment reversal design . Evidence from r and omised trials evaluating a pricing intervention or interventions restructuring several aspects of micro-environments was too scarce or inconsistent to be conclusive . The results from our qualitative comparative analysis supported the findings of this narrative synthesis . Interpretation Some interventions restructuring physical micro-environments could help to promote lower dem and for meat . Interventions reducing portion sizes of meat servings , providing meat alternatives , or changing the sensory properties of meat and meat alternatives at point of purchase offered the most promise in the context of experimental studies . Funding None |
779 | 24,446,384 | There is currently evidence of very low quality which is insufficient to support or refute subcutaneous closure after non-caesarean operations .
The use of subcutaneous closure has the potential to affect patient outcomes and utilisation of healthcare re sources . | BACKGROUND Most surgical procedures involve a cut in the skin that allows the surgeon to gain access to the surgical site .
Most surgical wounds are closed fully at the end of the procedure , and this review focuses on these .
The human body has multiple layers of tissues , and the skin is the outermost of these layers .
The loose connective tissue just beneath the skin is called subcutaneous tissue , and this generally contains fat .
There is uncertainty about closure of subcutaneous tissue after surgery : some surgeons advocate closure of subcutaneous tissue , as they consider this closes dead space and leads to a decrease in wound complications ; others consider closure of subcutaneous tissue to be an unnecessary step that increases operating time and involves the use of additional suture material without offering any benefit .
OBJECTIVES To compare the benefits ( such as decreased wound-related complications ) and consequences ( such as increased operating time ) of subcutaneous closure compared with no subcutaneous closure in participants undergoing non-caesarean surgical procedures . | Objective : To examine early results in patients with incision lines closed only along the skin and subcutaneous tissue after removal of the great saphenous vein during coronary artery bypass surgery . Material s and Methods : We enrolled 82 patients who underwent elective operations in our clinic between December 2008 and April 2009 . The patients had similar demographic characteristics , and the method of incision closure was chosen r and omly . Three patients were excluded due to in-hospital mortality . The saphenous incision lines were closed using continuous skin sutures in 41 patients ( Group 1 ) or using continuous subcutaneous sutures followed by continuous skin sutures in 38 patients ( Group 2 ) . Patients were followed every day that they were in the hospital , in the first week after being discharged , and at the end of the second month after discharge . The incision lines were evaluated for hematomas , infection , edema , pain and numbness . Results : During the follow-up performed in-hospital and in the first week after discharge , infection , edema and numbness were observed significantly more often in Group 2 than in Group 1 . Hematoma was observed more often in Group 1 , and pain was observed more often in Group 2 , but neither of these findings reached statistical significance . During the follow-up at the end of the second month after discharge , infection , edema , and numbness were observed significantly more frequently in Group 2 . Conclusion : In patients undergoing saphenous removal using st and ard procedures , it is sufficient to close the incision line using only skin sutures OBJECTIVE This study was undertaken to determine the most appropriate management of the subcutaneous tissue of midline vertical incisions with 3 cm or more of subcutaneous fat . STUDY DESIGN Patients undergoing surgery within the Division of Gynecologic Oncology at University of South Florida and East Tennessee State University with 3 cm or more of subcutaneous fat were r and omly assigned to 1 of 3 groups : suture approximation of Camper 's fascia , closed suction drainage of the subcutaneous space , or no intervention as a control group . Participants were evaluated daily during postoperative hospitalization and at 2 and 6 weeks postoperatively as an outpatient . Demographic information , perioperative data , and wound complications were recorded and then analyzed with chi2 , t test , analysis of variance , and logistic regression where appropriate . RESULTS Two hundred twenty-five patients were enrolled with 222 eligible for evaluation . Wound complications were observed in 34 ( 15.3 % ) patients , and 25 of these women also had wound disruption . Overall wound complication and wound disruption rates were not significantly different between groups : suture ( 12.8 % , 7.7 % ) , drain ( 17.9 % , 14.9 % ) , control ( 15.6 % , 11.7 % ) ; P = .70 and P = .39 , respectively . CONCLUSION Suture approximation or drainage of the subcutaneous tissues of women with 3 cm or more subcutaneous fat measured in midline vertical incisions result ed in no significant change in the incidence of overall wound complications or superficial wound disruption OBJECTIVE The aim of this study was to determine the effect of the depth of subcutaneous tissue at the operative site and the closure of subcutaneous tissue on abdominal wound disruption after cesarean delivery . METHODS 164 women divided into two groups : 70 with subcutaneous tissue thickness of at least 2 cm and 94 with subcutaneous tissue thickness more than 2 cm . These groups were r and omized to closure of the subcutaneous fat tissue or no closure with cesarean delivery . RESULTS In the 68 women with subcutaneous tissue thickness of at least 2 cm who completed the study , there was no difference between closure and no closure subgroups in terms of incidence of wound disruption . In 91 women with subcutaneous tissue thickness more than 2 cm who completed the study , the incidence of wound disruption was significantly higher in the no closure subgroup . In the no closure subgroup of 91 women with subcutaneous fat thickness more than 2 cm , the incidence of wound disruption was significantly higher than that of the 68 women with subcutaneous tissue thickness at least 2 cm . CONCLUSIONS Subcutaneous tissue approximation with absorbable suture at closure of the abdominal incision during cesarean delivery appears to reduce the rate of postoperative wound disruption in patients with more than 2 cm of subcutaneous tissue Background : The objective of this study was to compare the cosmetic outcome of facial lacerations closed with a single or double layer of sutures . Methods : Patients aged 1 year or older presenting to a university-based emergency department with nongaping ( width , < 10 mm ) , simple , nonbite , facial lacerations were r and omized to closure with a single layer of simple interrupted 6 - 0 polypropylene sutures or a double layer of simple interrupted 6 - 0 polypropylene plus inverted deep dermal 5 - 0 polyglactin sutures . At 90 days , the scar width and cosmetic appearance were determined using a vali date d 100-mm visual analogue scale ranging from 0 ( worst ) to 100 ( best ) and a vali date d wound evaluation score ranging from 0 ( worst ) to 6 ( best ) . Results : Sixty-five patients were r and omized to single-layer ( n = 32 ) or double-layer ( n = 33 ) closure . Mean age ( SD ) was 18.5 years ( 20.0 ) , and 14 percent were female . Groups were similar in baseline patient and wound characteristics . Length of single-layer closure was 7 minutes shorter ( 95 percent CI , 2 to 11 minutes ) than double-layer closure . There were no infections or dehiscences in either group . There were no between-group differences in patient ( mean difference , 0.5 mm ; 95 percent CI , –5.7 to 6.6 mm ) or practitioner ( mean difference , 1.0 mm ; 95 percent CI , –4.8 to 6.7 mm ) visual analogue scale scores . All but one patient had an optimal wound evaluation score of 6 ( p = not significant ) . Scar width was similar at 90 days ( mean difference , 0.2 mm ; 95 percent CI , –0.05 to 0.5 ) . Conclusions : Single-layer closure of nongaping , minor ( <3 cm ) facial lacerations is faster than double-layer closure . Cosmetic outcome and scar width are similar in sutured wounds whether or not deep dermal sutures are used Purpose : The aim of this prospect i ve r and omized study was to investigate the necessity of suturing subcutaneous fat tissue in elective abdominal surgery . Methods : 415 patients undergoing elective abdominal surgery were admitted to the trial . The patients were divided into two basic groups according to wound contamination : clean operations ( n = 201 ) and clean-contaminated operation ( n = 214 ) . Subcutaneous suturing of the subcutaneous fat tissue was performed in half of the patients in each group , determined using the envelope method ( ‘ Suture Yes ’ or ‘ Suture No ’ ) . Wounds were checked on postoperative days 3 , 7 , 14 , and 30 . Infectious and non-infectious wound complications were charted in the records . Data were statistically analyzed . The percentages of complications in groups with and without subcutaneous suturing were statistically compared using Yates ’ corrected χ2 two-tailed test . Results : There were no statistically significant group differences in infectious and non-infectious wound complications . Conclusion : These results suggest that omission of subcutaneous fat tissue suturing does not increase the occurrence of infectious or non-infectious wound complications Purpose Surgical site infections ( SSI ) cause excess morbidity and mortality in modern surgery . Several different approaches to reduce the incidence of SSI have been investigated with variable results . Method This is to our knowledge the first systematic r and omized evaluation in patients undergoing laparotomy in visceral surgery to clarify whether widely used subcutaneous drains ( Redon ) affect wound infection as the primary outcome measure . Results In 200 patients , we were unable to show a statistically significant impact on the postoperative healing process in patients with the full variety of abdominal surgical interventions . Overall , we observed surgical site infection in 9.5 % of all patients ( n = 19 ) , of these n = 9 ( 47.4 % ) were in the control group without a drain , and 10 ( 52.6 % ) were in the experimental group with a Redon drain ( not significant ) . Conclusion As this study could not demonstrate a reduction of SSI by the use of Redon drains , there is no indication for prophylactic subcutaneous suction drains after laparotomy AIMS To evaluate the role of subcutaneous tissue closure in relation to wound disruption after abdominal hysterectomy in obese patients . MATERIAL AND METHODS In a prospect i ve study at a tertiary referral centre in Mumbai , India , 60 obese patients with subcutaneous fat more than 2.5 cms were included in the study . In 30 patients , subcutaneous tissue was closed using synthetic suture ( dexon ) while in 30 control patients subcutaneous tissue was not closed . Average weight in the study and control groups were 69 -/+ 9.2 kg and 63.3 -/+ 11.2 kg respectively . RESULTS The wound disruption occurred in 5 patients in non-closure group as compared to only one in the closure group . Incidence of seroma , haematoma formation and other wound complications were higher in the non-closure group . CONCLUSIONS Closure of the subcutaneous tissue after abdominal hysterectomy of women with at least 2.5 cms of subcutaneous tissue lowers the overall rate of complications leading to disruption of the incision Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . BACKGROUND Wound infection and dehiscence are both major contributors to postoperative morbidity . One potential cause or co-factor is the use of suture material . A recently introduced subcutaneous suture is coated with triclosan ( TC ) , an antiseptic drug . It is suggested to reduce wound complications . METHODS To investigate the effect of TC on wound healing a double blind prospect i ve pilot study in women undergoing a breast reduction was performed . Each patient was her own control . After r and omisation the TC-coated sutures were used either on the left or right side . The contralateral side was used as the control . The incidence of dehiscence was studied . RESULTS Twenty-six patients were included . In the TC breasts there was a wound dehiscence in 16 cases , whereas in the control breasts in seven cases a dehiscence was observed ( P=0.023 ) . CONCLUSION These results suggest that TC-coated sutures should be used with caution . These sutures have already been introduced on to the market without good clinical studies and might have potential adverse effects as shown by these data Wound haematoma is an undesirable complication of surgery . We report a prospect i ve trial to establish whether a subcutaneous fat stitch affects haematoma formation in hip surgery . A series of 50 patients undergoing hip surgery were r and omised to have either a fat stitch or no fat stitch during wound closure . The wounds were assessed clinical ly with a minimum follow-up of 5 weeks . Subcutaneous haematomas were seen more easily with the patient st and ing . As clinical assessment for haematoma formation may be unreliable , each patient also had an ultrasound scan . Although the incidence of subcutaneous haematoma was slightly higher in the no fat stitch group ( 36 % compared with 24 % in the fat stitch group ) this difference was not statistically significant ( chi 2 test , P < 0.5 ) . There were no significant differences in the incidence of wound infection and healing rate . From our study we also showed that ultrasound examination was twice as sensitive as clinical examination in diagnosing subcutaneous haematomas and that subcutaneous haematomas are common after hip surgery We report a prospect i ve trial to establish whether a subcutaneous fat stitch reduces the incidence of haematoma formation , infection and wound dehiscence following saphenous vein excision for coronary revascularization . Two groups of patients undergoing coronary revascularization were studied . In the first group of 100 patients the saphenous vein was harvested from both legs . Legs were r and omized to have either a fat stitch or no fat stitch during wound closure . By using both legs of each patient we eliminated the effect of general factors on wound healing , thus the patients acted as their own controls . In the second group of 200 patients , the saphenous vein was harvested from the thigh , and patients r and omly allocated to either a fat stitch or no fat stitch during wound closure . The wounds were examined daily for 7 days , and again after 6 weeks at the follow-up . There was no difference in the rate of wound complication in the fat stitch groups ( 9 % ) compared with the no fat stitch groups ( 8 % ) , however , the fat stitch groups required more surgical intervention for skin edge necrosis . It appears that closure of the subcutaneous fat following saphenectomy is unnecessary , and may be detrimental to skin healing Objective . The aim of the study was to evaluate the impact of an additional subcutaneous suture line on the incidence of postoperative ( p.o . ) infection at the vena saphena magna harvesting site ( VSMHS ) after coronary artery bypass grafting ( CABG ) . Methods . Two hundred and forty three patients undergoing CABG were included . Patients in Group A ( n = 119 ) all operated by one physical assistant ( PA ) were prospect ively r and omised into Group A1 ( n = 59 ) receiving intracutaneous closure suture alone whereas 60 patients ( Group A2 ) received an additional subcutaneous suture line . Group B ( n = 120 ) , operated by surgical residents , served as control population . All patients were due to follow-up at six weeks p.o . Results . Subcutaneous suture did not impact the p.o . infection rate ( A2 vs. A1 ; 4/60 vs. 2/59 , n.s . ) . A significant lower p.o . infection rate was observed in Group A vs. Group B ( 6/119 ( 5 % ) vs. 15/120 ( 13 % ) p < 0.05 ) . Conclusion . Subcutaneous suture did not impact the p.o . infection rate at VSMHS . The infection rate observed in patients operated by an experienced PA was significantly lower than in patients operated by various surgical residents Objective To test the hypothesis that closure of the subcutaneous fat decreases the incidence of wound disruption after cesarean delivery . Methods Two hundred forty-five women with at least 2 cm of subcutaneous fat were r and omized to closure of the Camper fascia or no closure with cesarean delivery . Results Complications leading to disruption or opening of the incision were classified as wound seromas in 28 women ( 11.4 % ) and as wound infections in 17 ( 7.0 % ) . The relative risk ( RR ) of seroma formation in the subcutaneous closure group was 0.3 with a 95 % confidence interval ( CI ) of 0.1–0.7 ( 5.1 versus 17.2 % ) , a statistically significant difference . There was no significant difference in the incidence of wound infections in the two study groups . Overall , there was a significant difference in the incidence of wound disruption from all causes between the two groups : 14.5 % in the subcutaneous closure group compared with 26.6 % when the subcutaneous tissues were not reapproximated ( RR 0.5 , 95 % CI = 0.3–0.9 ) . Conclusion Closure of the subcutaneous tissue can significantly reduce the rate of postoperative wound disruption in women with at least 2 cm of subcutaneous adipose tissue OBJECTIVE To investigate the impact of postdischarge surveillance ( PDS ) on surgical-site infection ( SSI ) rates for selected surgical procedures in acute care hospitals in Scotl and . DESIGN Prospect i ve surveillance of SSI after selected surgical procedures . SETTING The Scottish Surveillance of Healthcare Associated Infection Programme ( SSHAIP ) , which is based on the methodology of the Centers for Disease Control and Prevention ( CDC ) National Nosocomial Infections Surveillance system ( NNIS ) . Thirty-two of 46 acute care hospitals throughout Scotl and contributed data to SSHAIP for this study . METHODS Data were from 21,710 operations that took place between April 1 , 2002 , and June 30 , 2004 ; nine categories of surgical procedures were analyzed . CDC NNIS system definitions and methods were used for SSI PDS . PDS is a voluntary component of the m and atory SSI surveillance program in Scotl and . PDS was categorized as none , passive , active without direct observation , and active with direct observation . RESULTS From our study information , PDS data were available for 12,885 operations ( 59 % ) . A total of 2,793 procedures ( 13 % ) were associated with passive PDS and 10,092 ( 46 % ) with active PDS . The SSI rate among the 8,825 operations with no PDS was 2.61 % ( 95 % confidence interval [ CI ] , 2.3%-3.0 % ) , which was significantly lower than the SSI rate found among the 12,885 operations for which PDS was performed ( 6.34 % [ 95 % CI , 5.9%-6.8 % ] ) . For breast surgery , cesarean section , hip replacement , and abdominal hysterectomy , the rate of SSI when PDS was performed was significantly higher than that when PDS was not performed ( P<.01 for each procedure ) . No differences in SSI rates were found for surgery to repair fractured neck of the femur or for knee replacement . SSI rates were examined according to procedure type , performance of PDS , and NNIS risk index ; rates of SSI increased with NNIS risk index within procedure group and PDS group . Logistic regression analyses confirmed that procedure type , performance of PDS , and NNIS risk index were all statistically independent predictors of report of an SSI ( P<.05 ) . CONCLUSIONS This Scottish national data set incorporates a substantial amount of PDS data . We recommend a procedure-specific approach to PDS , with direct observation of patients after breast surgery , cesarean section , and hysterectomy , for which the length of stay is typically short . Readmission surveillance may be adequate to detect most SSIs after orthopedic surgery or vascular surgery , for which the length of stay is typically longer OBJECTIVE Surgical site infections after cardiothoracic surgery substantially increase the risk for illness , mortality , and costs . Surveillance of surgical site infections might assist in the prevention of these infections . This study describes the Dutch surveillance methods and results of data collected between 2002 and 2007 . METHODS Three cardiothoracic procedures were included : coronary artery bypass graft procedures , valve surgery , and a combination of coronary artery bypass graft procedures with concomitant valve surgery . The surgical site infections were divided into sternal and harvest-site infections . Postdischarge surveillance of surgical site infections was m and atory for sternal wounds and elective for harvest-site wounds , with a follow-up period of 42 postoperative days . Multivariate logistic regression was used for risk factor analysis of coronary artery bypass grafts , with adjustment for r and om variation among hospitals . RESULTS Eight of the 16 Dutch cardiothoracic centers participated and collected data on 4066 procedures and 183 surgical site infections , revealing a surgical site infection rate of 2.4 % for sternal wounds and 3.2 % for harvest sites . Sixty-one percent of all surgical site infections were recorded after discharge . For sternal surgical site infections after coronary artery bypass graft procedures , the significant risk factors were rethoracotomy , diabetes , preoperative length of stay , and obesity ; for harvest-site infections , the most relevant risk factor was a long time on extracorporeal circulation . Adjusted surgical site infection rates regarding coronary artery bypass graft procedures varied between hospitals from 0.0 % to 9.7 % . CONCLUSIONS Large differences were found in surgical site infection rates between Dutch hospitals , which indicate room for improvement . The follow-up of patients after hospital discharge reduces underestimation of surgical site infection rates Two hundred and eight consecutive patients undergoing surgery were allocated r and omly in a trial of the use of a plain catgut subcutaneous fat stitch , compared with no fat suture . There was no appreciable difference between the two trial groups in wound infection rate following either clean ( 4 out of 74 with and 1 out of 68 without a fat stitch ) or contaminated operations ( 4 out of 27 with and 4 out of 41 without ) . Likewise , there were no differences in haematoma rates . There is therefore no appreciable benefit to be derived from the use of this stitch OBJECTIVE We conducted an intervention study to assess the impact of the use of an alcohol-chlorhexidine-based h and sanitizer on surgical site infection ( SSI ) rates among neurosurgical patients in Ho Chi Minh City , Vietnam . DESIGN A quasi-experimental study with an untreated control group and assessment of neurosurgical patients admitted to 2 neurosurgical wards at Cho Ray Hospital between July 11 and August 15 , 2000 ( before the intervention ) , and July 14 and August 18 , 2001 ( after the intervention ) . A h and sanitizer with 70 % isopropyl alcohol and 0.5 % chlorhexidine gluconate was introduced , and healthcare workers were trained in its use on ward A in September 2000 . No intervention was made in ward B. Centers for Disease Control and Prevention definitions of SSI were used . Patient SSI data were collected on st and ardized forms and were analyzed using Stata software ( Stata ) . RESULTS A total of 786 patients were enrolled : 377 in the period before intervention ( 156 in ward A and 221 in ward B ) and 409 in the period after intervention ( 159 in ward A and 250 in ward B ) . On ward A after the intervention , the SSI rate was reduced by 54 % ( from 8.3 % to 3.8 % ; P=.09 ) , and more than half of superficial SSIs were eliminated ( 7 of 13 vs 0 of 6 in ward B ; P=.007 ) . On ward B , the SSI rate increased by 22 % ( from 7.2 % to 9.2 % ; P=.8 ) . In patients without SSI , the median postoperative length of stay and the duration of antimicrobial use were reduced on ward A ( both from 8 to 6 days ; P<.001 ) but not on ward B. CONCLUSIONS Our study demonstrates that introduction of a h and sanitizer can both reduce SSI rates in neurosurgical patients , with particular impact on superficial SSIs , and reduce the overall postoperative length of stay and the duration of antimicrobial use . H and hygiene programs in developing countries are likely to reduce SSI rates and improve patient outcomes |
780 | 26,037,486 | Neither study reported on QoL. AUTHORS ' CONCLUSIONS Compared with DNR in induction therapy of newly diagnosed AML , IDA prolongs OS and DFS , increases CR rate and reduces relapse rate , although increases the risks of death on induction therapy and grade 3/4 mucositis .
The currently available evidence does not show any difference between IDA and MIT used in induction therapy of newly diagnosed AML .
Additionally , there is no evidence for difference on the effect of IDA compared with DNR , MIT , DOX or ZRB on | BACKGROUND Anthracycline combined with cytarabine has been the st and ard for induction therapy of newly diagnosed acute myeloid leukaemia ( AML ) for several decades .
Due to theoretical advantages , idarubicin ( IDA ) might be the most effective and tolerable anthracycline .
However , there is no evidence that would definitively prove the superiority of IDA over other anthracyclines .
OBJECTIVES To assess the efficacy and safety of IDA versus other anthracyclines in induction therapy of newly diagnosed AML . | PURPOSE Identifying true therapeutic progress in patients with acute myeloid leukemia ( AML ) requires a comparison of treatment strategies and results on the basis of uniform patient selection . To foster comparability across five clinical studies , we introduced a common st and ard arm combined with a general upfront r and omization and performed prospect i ve analyses with adjustment for differences in prognostic baseline characteristics . PATIENTS AND METHODS Whereas the studies ' own regimens differed in chemotherapies , risk adaption , and guidelines for allogeneic stem-cell transplantation , the st and ard arm contained uniform cytarabine- and anthracycline-based st and ard-dose remission induction and high-dose consolidation courses . RESULTS Of 2,995 evaluable patients aged 16 to 60 years , 290 patients were r and omly assigned to the common st and ard arm . Seventy percent of the 290 achieved complete remissions ( 62 % with complete recovery , 8 % with incomplete recovery ; 95 % CI , 65 % to 76 % ) . Five-year survival probabilities were 44.3 % ( 95 % CI , 37.7 % to 50.7 % ) for overall survival , 44.8 % ( 95 % CI , 37.0 % to 52.2 % ) for relapse-free survival , and 31.5 % ( 95 % CI , 25.7 % to 37.4 % ) for event-free survival . Neither the unadjusted survival probabilities of the Kaplan-Meier method nor their adjustment for prognostic variables in multiple Cox regression models led to statistically significant different results in the three survival end points when the outcomes of each study were compared with the st and ard arm . CONCLUSION A strictly prospect i ve comparison of different treatment strategies in patients with AML did not show clinical ly relevant outcome differences when compared through a common st and ard treatment arm . The results provide a representative basis for further therapeutic approaches The optimal induction for older adults with acute myeloid leukemia ( AML ) is unknown . Several anthracyclines have been proposed , but the data remain equivocal . Additionally , few prospect i ve trials of priming with hematopoietic growth factors to cycle leukemia cells prior to induction chemotherapy have been conducted . Three hundred and sixty-two older adults with previously untreated AML were r and omized to either daunorubicin , idarubicin or mitoxantrone with a st and ard dose of cytarabine as induction therapy . In addition , 245 patients were also r and omized to receive granulocyte-macrophage colony-stimulating factor ( GM-CSF ) or placebo beginning 2 days prior to induction chemotherapy and continuing until marrow aplasia . No difference was observed in the disease-free overall survival or in toxicity among patients receiving any of the 3 induction regimens or among those receiving growth factor or placebo for priming . However , the complete remission rate for the first 113 analyzable patients , who did not participate in the priming study and started induction therapy 3 to 5 days earlier than those who did , was significantly higher ( 50 % versus 38 % ; P = .03 ) . None of the anthracyclines is associated with improved outcome in older adults . Priming with hematopoietic growth factor did not improve response when compared with placebo . Furthermore , delaying induction therapy in older adults may lead to a lower complete remission rate The first EORTC ( European Organization of Research and Treatment of Cancer ) acute myeloblastic leukemia ( AML ) pilot study ( 58872 ) was conducted between January 1988 and December 1991 . Out of 108 patients , 78 % achieved complete remission ( CR ) , and event-free survival ( EFS ) and survival rates ( s.e . , % ) at 7 years were 40 ( 5 ) and 51 % ( 6 % ) , respectively . It indicated that mitoxantrone could be substituted for conventional anthracyclines in the treatment of childhood AML without inducing cardiotoxicity . The aim of the next EORTC 58921 trial was to compare the efficacy and toxicity of idarubicin vs mitoxantrone in initial chemotherapy courses , further therapy consisting of allogeneic bone marrow transplantation ( alloBMT ) in patients with an HLA-compatible sibling donor or chemotherapy in patients without a donor . Out of 177 patients , recruited between October 1992 and December 2002 , 81 % reached CR . Overall 7-year EFS and survival rates were 49 ( 4 ) and 62 % ( 4 % ) , respectively . Out of 145 patients who received the first intensification , 39 had a sibling donor . In patients with or without a donor , the 7-year disease-free survival ( DFS ) rate was 63 ( 8) and 57 % ( 5 % ) and the 7-year survival rate was 78 ( 7 ) and 65 % ( 5 % ) , respectively . Patients with favorable , intermediate and unfavorable cytogenetic features had a 5-year EFS rate of 57 , 45 and 45 % and a 5-year survival rate of 89 , 67 and 53 % , respectively CCG-2961 incorporated 3 new agents , idarubicin , fludarabine and interleukin-2 , into a phase 3 AML trial using intensive-timing remission induction/consolidation and related donor marrow transplantation or high-dose cytarabine intensification . Among 901 patients under age 21 years , 5-year survival was 52 % , and event-free survival was 42 % . Survival improved from 44 % between 1996 and 1998 to 58 % between 2000 and 2002 ( P = .005 ) , and treatment-related mortality declined from 19 % to 12 % ( P = .025 ) . Partial replacement of daunomycin with idarubicin in the 5-drug induction combination achieved a remission rate of 88 % , similar to historical controls . Postremission survival was 56 % in patients r and omized to either 5-drug reinduction or fludarabine/cytarabine/idarubicin . For patients with or without a related donor , respective 5-year disease-free survival was 61 % and 50 % ( P = .021 ) ; respective survival was 68 % and 62 % ( P = .425 ) . Donor availability conferred no benefit on those with inv(16 ) or t(8;21 ) cytogenetics . After cytarabine intensification , patients r and omized to interleukin-2 or none experienced similar outcomes . Factors predictive of inferior survival were age more than 16 years , non-white ethnicity , absence of related donor , obesity , white blood cell count more than 100 000 x 10(9)/L , -7/7q- , -5/5q- , and /or complex karyotype . No new agent improved outcomes ; experience may have contributed to better results time PURPOSE To compare the antitumor efficacy of three different anthracyclines in combination with cytarabine and etoposide in adult patients with newly diagnosed acute myeloid leukemia ( AML ) . PATIENTS AND METHODS We r and omly assigned 2,157 patients ( age range , 15 to 60 years ) to receive intensive induction-consolidation chemotherapy containing either daunorubicin , idarubicin , or mitoxantrone . After achieving complete remission ( CR ) , patients were assigned to undergo either allogeneic or autologous stem-cell transplantation ( SCT ) , depending on the availability of a sibling donor . RESULTS The overall CR rate ( 69 % ) was similar in the three groups . Autologous SCT was performed in 37 % of cases in the daunorubicin arm versus only 29 % and 31 % in mitoxantrone and idarubicin , respectively ( P < .001 ) . However , the disease-free survival ( DFS ) and survival from CR were significantly shorter in the daunorubicin arm : the 5-year DFS was 29 % versus 37 % and 37 % in mitoxantrone and idarubicin , respectively . The proportion of patients who underwent allogeneic SCT ( 22 % ) was equivalent in the three treatment groups , and the outcome was similar as well . The [ corrected ] 5-year overall survival rates were 31 % , 34 % , and 34 % , [ corrected ] respectively . CONCLUSION In adult patients with AML who do not receive an allogeneic SCT , the use of mitoxantrone or idarubicin instead of daunorubicin enhances the long-term efficacy of chemotherapy BACKGROUND A complete remission is essential for prolonging survival in patients with acute myeloid leukemia ( AML ) . Daunorubicin is a cornerstone of the induction regimen , but the optimal dose is unknown . In older patients , it is usual to give daunorubicin at a dose of 45 to 50 mg per square meter of body-surface area . METHODS Patients in whom AML or high-risk refractory anemia had been newly diagnosed and who were 60 to 83 years of age ( median , 67 ) were r and omly assigned to receive cytarabine , at a dose of 200 mg per square meter by continuous infusion for 7 days , plus daunorubicin for 3 days , either at the conventional dose of 45 mg per square meter ( 411 patients ) or at an escalated dose of 90 mg per square meter ( 402 patients ) ; this treatment was followed by a second cycle of cytarabine at a dose of 1000 mg per square meter every 12 hours [ DOSAGE ERROR CORRECTED ] for 6 days . The primary end point was event-free survival . RESULTS The complete remission rates were 64 % in the group that received the escalated dose of daunorubicin and 54 % in the group that received the conventional dose ( P=0.002 ) ; the rates of remission after the first cycle of induction treatment were 52 % and 35 % , respectively ( P<0.001 ) . There was no significant difference between the two groups in the incidence of hematologic toxic effects , 30-day mortality ( 11 % and 12 % in the two groups , respectively ) , or the incidence of moderate , severe , or life-threatening adverse events ( P=0.08 ) . Survival end points in the two groups did not differ significantly overall , but patients in the escalated-treatment group who were 60 to 65 years of age , as compared with the patients in the same age group who received the conventional dose , had higher rates of complete remission ( 73 % vs. 51 % ) , event-free survival ( 29 % vs. 14 % ) , and overall survival ( 38 % vs. 23 % ) . CONCLUSIONS In patients with AML who are older than 60 years of age , escalation of the dose of daunorubicin to twice the conventional dose , with the entire dose administered in the first induction cycle , effects a more rapid response and a higher response rate than does the conventional dose , without additional toxic effects . ( Current Controlled Trials number , IS RCT N77039377 ; and Netherl and s National Trial Register number , NTR212 . Between 1990 and 1996 , we conducted a r and omized trial in adults with newly diagnosed acute myeloid leukemia ( AML ) in order to compare relapse-free interval ( RFI ) after double induction ( arm B ) , timed-sequential induction ( arm C ) , or control " 3 + 7 " induction ( arm A ) . Patients achieving complete remission ( CR ) after induction + /- salvage received the same consolidation chemotherapy , which included a dosage stratification according to patient 's age ( younger or older than 50 years ) . This long-term analysis was performed in 592 patients ( arm A/B/C , 197/198/197 patients ) . Overall CR rate was 76 % without differences between the 3 arms , even if a salvage course was less frequently needed in arm B. Treatment-related mortality , either during the induction or the postremission phase , was not significantly higher in arms B and C than in arm A. Among the 449 CR patients , 250 relapsed ( arm A/B/C , 90/87/73 patients ) without significant differences in RFI in arms B and C versus arm A ( P = .39 and .15 , by the Gray test ) . However , when analyzing the 345 patients younger than 50 , RFI was significantly improved in younger patients receiving timed-sequential induction ( P = .038 by the Gray test ) , while not in those receiving double induction . Event-free survival and overall survival were similar in the 3 r and omization arms PURPOSE In patients with acute myeloid leukemia ( AML ) , induction chemotherapy is based on st and ard doses of anthracyclines and cytarabine . High doses of cytarabine have been reported as being too toxic for patients older than age 50 years , but few studies have evaluated intensified doses of anthracyclines . PATIENTS AND METHODS In this r and omized Acute Leukemia French Association 9801 ( ALFA-9801 ) study , high doses of daunorubicin ( DNR ; 80 mg/m(2)/d x 3 days ) or idarubicin ( IDA4 ; 12 mg/m(2)/d x 4 days ) were compared with st and ard doses of idarubicin ( IDA3 ; 12 mg/m(2)/d x 3 days ) for remission induction in patients age 50 to 70 years , with an event-free survival ( EFS ) end point . After two consolidation courses based on intermediate doses of cytarabine , patients in continuous remission were r and omly assigned to receive or not receive maintenance therapy with recombinant interleukin-2 ( rIL-2 ; 5 x 10(6 ) U/m(2 ) x 5 days each month ) for a total duration of 12 months . A total of 468 patients entered the study ( median age , 60 years ) . Results Overall complete remission rate was 77 % with significant differences among the three r and omization arms ( 83 % , 78 % , and 70 % in the IDA3 , IDA4 , and DNR arms , respectively ; P = .04 ) . However , no significant differences were observed in relapse incidence , EFS , or overall survival among the three arms . In the 161 patients r and omly assigned for maintenance therapy , no difference in outcome was observed between the rIL-2 and the no further treatment arms . CONCLUSION Neither intensification of anthracycline doses nor maintenance with rIL-2 showed a significant impact on AML course , at least as scheduled in this trial Outcomes of patients with acute myeloid leukemia ( AML ) improve significantly by intensification of induction . To further intensify anthracycline dosage without increasing cardiotoxicity , we compared potentially less cardiotoxic liposomal daunorubicin ( L-DNR ) to idarubicin at a higher-than-equivalent dose ( 80 vs 12 mg/m(2 ) per day for 3 days ) during induction . In the multicenter therapy-optimization trial AML-BFM 2004 , 521 of 611 pediatric patients ( 85 % ) were r and omly assigned to L-DNR or idarubicin induction . Five-year results in both treatment arms were similar ( overall survival 76 % ± 3 % [ L-DNR ] vs 75 % ± 3 % [ idarubicin ] , Plogrank = .65 ; event-free survival [ EFS ] 59 % ± 3 % vs 53 % ± 3 % , Plogrank = .25 ; cumulative incidence of relapse 29 % ± 3 % vs 31 % ± 3 % , P(Gray ) = .75 ) , as were EFS results for st and ard ( 72 % ± 5 % vs 68 % ± 5 % , Plogrank = .47 ) and high-risk ( 51 % ± 4 % vs 46 % ± 4 % , Plogrank = .45 ) patients . L-DNR result ed in significantly better probability of EFS in patients with t(8;21 ) . Overall , treatment-related mortality was lower with L-DNR than idarubicin ( 2/257 vs 10/264 patients , P = .04 ) . Grade 3/4 cardiotoxicity was rare after induction ( 4 L-DNR vs 5 idarubicin ) . Only 1 L-DNR and 3 idarubicin patients presented with sub clinical or mild cardiomyopathy during follow-up . In conclusion , at the given dose , L-DNR has overall antileukemic activity comparable to idarubicin , promises to be more active in subgroups , and causes less treatment-related mortality . This trial was registered at www . clinical trials.gov as # NCT00111345 We conducted a multi-institutional r and omized study to determine whether high-dose daunorubicin would be as effective as st and ard-dose idarubicin in remission-induction therapy for newly diagnosed adult patients younger than 65 years of age with acute myeloid leukemia . Of 1064 patients registered , 1057 were evaluable . They were r and omly assigned to receive either daunorubicin ( 50 mg/m(2 ) daily for 5 days ) or idarubicin ( 12 mg/m(2 ) daily for 3 days ) in combination with 100 mg/m(2 ) of cytarabine by continuous infusion daily for 7 days as induction therapy . Complete remission was achieved in 407 ( 77.5 % ) of 525 patients in the daunorubicin group and 416 ( 78.2 % ) of 532 in the idarubicin group ( P = .79 ) . Patients achieving complete remission received intensive postremission therapy that consisted of either 3 courses of high-dose cytarabine or 4 courses of st and ard-dose therapy . Overall survival rates at 5 years were 48 % for the daunorubicin group and 48 % for the idarubicin group ( P = .54 ) , and relapse-free survival rates at 5 years were 41 % and 41 % ( P = .97 ) , respectively . Thus , high-dose daunorubicin and st and ard-dose idarubicin were equally effective for the treatment of adult acute myeloid leukemia , achieving a high rate of complete remission and good long-term efficacy . This study is registered at http://www.umin.ac.jp/ctrj/ as C000000157 In elderly patients with acute myeloid leukemia ( AML ) treated intensively , no best postremission strategy has emerged yet . This clinical trial enrolled 416 patients with AML aged 65 years or older who were considered eligible for st and ard intensive chemotherapy , with a first r and omization comparing idarubicin with daunorubicin for all treatment sequences . After induction , an ambulatory postremission strategy based on 6 consolidation cycles administered monthly in out patients was r and omly compared with an intensive strategy with a single intensive consolidation course similar to induction . Complete remission ( CR ) rate was 57 % with 10 % induction deaths , and estimated overall survival was 27 % at 2 years and 12 % at 4 years , without notable differences between anthracycline arms . Among the 236 patients who reached CR , 164 ( 69 % ) were r and omized for the postremission comparison . In these patients , the multivariate odds ratio in favor of the ambulatory arm was 1.51 for disease-free survival ( P.05 ) and 1.59 for overall survival from CR ( P.04 ) . Despite repeated courses of chemotherapy associated with a longer time under treatment , the ambulatory arm was associated with significantly shorter rehospitalization duration and lower red blood cell unit and platelet transfusion requirements than observed in the intensive arm . In conclusion , more prolonged ambulatory treatment should be preferred to intensive chemotherapy as postremission therapy in elderly patients with AML reaching CR after st and ard intensive remission induction OBJECTIVE To evaluate the efficacy and safety of IDA ( Haizheng Parmacy , China ) in the treatment of acute leukemia . METHODS A multi-institutional single-blind r and omized controlled clinical trial was carried out . A total of 155 newly diagnosed patients with AML and ALL were enrolled . The patients were r and omly divided into two groups , one was given IDA ( n = 77 ) and the other given zevodas ( Pharnacia & Upjohn , n = 78 ) for comparison . RESULTS All the patients enrolled in this trial were eligible for assessment of side effects , and 129 patients for evaluation of overall response rate . In patients treated with IDA vs zevodas , the overall response rate ( OR ) was 78.1 % vs 76.9 % , CR was 68.8 % vs 67.7 % ; in AML patients , OR was 82.4 % vs 71.8 % , and CR was 76.5 % vs 64.1 % ; in ALL patients , OR was 80.0 % vs 81.8 % , and CR was 68.0 % vs 68.2 % . There was no sitatistically significant difference in hematologic and non-hematologic toxicities between the two groups . CONCLUSION The efficacy of IDA in the treatment of acute leukemia is comparable to that of zevodas . Both have similar toxic side effects BACKGROUND Allogeneic or autologous bone marrow transplantation and intensive consolidation chemotherapy are used to treat acute myelogenous leukemia in a first complete remission . METHODS After induction treatment with daunorubicin and cytarabine , patients who had a complete remission received a first course of intensive consolidation chemotherapy , combining intermediate-dose cytarabine and amsacrine . Patients with an HLA-identical sibling were assigned to undergo allogeneic bone marrow transplantation ; the others were r and omly assigned to undergo autologous bone marrow transplantation ( with unpurged bone marrow ) or a second course of intensive chemotherapy , combining high-dose cytarabine and daunorubicin . Comparisons were made on the basis of the intention to treat . RESULTS A total of 623 patients had a complete remission ; 168 were assigned to undergo allogeneic bone marrow transplantation , and 254 were r and omly assigned to one of the other two groups . Of these patients , 343 completed the treatment assignment : 144 in the allogeneic-transplantation group , 95 in the autologous-transplantation group , and 104 in the intensive-chemotherapy group . The relapse rate was highest in the intensive-chemotherapy group and lowest in the allogeneic-transplantation group , whereas the mortality rate was highest after allogeneic transplantation and lowest after intensive chemotherapy . The projected rate of disease-free survival at four years was 55 percent for allogeneic transplantation , 48 percent for autologous transplantation , and 30 percent for intensive chemotherapy . However , the overall survival after complete remission was similar in the three groups , since more patients who relapsed after a second course of intensive chemotherapy had a response to subsequent autologous bone marrow transplantation . Other differences were also observed , especially with regard to hematopoietic recovery ( it occurred later after autologous transplantation ) and the duration of hospitalization ( it was longer with bone marrow transplantation ) . CONCLUSIONS Autologous as well as allogeneic bone marrow transplantation results in better disease-free survival than intensive consolidation chemotherapy with high-dose cytarabine and daunorubicin . Transplantation soon after a relapse or during a second complete remission might also be appropriate PURPOSE Although st and ard chemotherapy remains associated with a poor outcome in older patients with acute myeloid leukemia ( AML ) , it is unclear which patients can survive long enough to be considered as cured . This study aim ed to identify factors influencing the long-term outcome in these patients . PATIENTS AND METHODS The study included 727 older patients with AML ( median age , 67 years ) treated in two idarubicin ( IDA ) versus daunorubicin ( DNR ) Acute Leukemia French Association trials . Prognostic analysis was based on st and ard univariate and multivariate models and also included a cure fraction model to focus on long-term outcome . RESULTS Age , WBC count , secondary AML , Eastern Cooperative Oncology Group ( ECOG ) performance status ( PS ) , and adverse-risk and favorable-risk AML subsets ( European LeukemiaNet classification ) all influenced complete remission ( CR ) rate and overall survival ( OS ) . IDA r and om assignment was associated with higher CR rate , but not with longer OS ( P = .13 ) . The overall cure rate was 13.3 % . Older age and ECOG-PS more than 1 negatively influenced cure rate , which was higher in patients with favorable-risk AML ( 39.1 % v 8.0 % in adverse-risk AML ; P < .001 ) and those treated with IDA ( 16.6 % v 9.8 % with DNR ; P = .018 ) . The long-term impact of IDA was still observed in patients younger than age 65 years , although all of the younger patients in the DNR control arm received high DNR doses ( cure rate , 27.4 % for IDA v 15.9 % for DNR ; P = .049 ) . In multivariate analysis , IDA r and om assignment remained associated with a higher cure rate ( P = .04 ) , together with younger age and favorable-risk AML , despite not influencing OS ( P = .11 ) . CONCLUSION In older patients with AML , younger age , favorable-risk AML , and IDA treatment predict a better long-term outcome Despite improvements in the treatment of acute myeloid leukemia ( AML ) , approximately 50 % of children die of the disease . Clinical trials in adult patients with AML indicate that idarubicin may have superior efficacy when compared to daunorubicin in the remission-induction phases of chemotherapy . We conducted consecutive clinical trials in children with newly diagnosed AML in which daunorubicin ( group 1 , n = 102 ) or idarubicin ( group 2 , n = 160 ) was used during the remission-induction ( RI ) and the early consolidation phases of chemotherapy . Idarubicin was given at a dose of either 10 mg/m(2 ) ( group 2A , n = 106 ) or 12 mg/m(2 ) ( group 2B , n = 53 ) . A high rate of RI was achieved for all groups ( 95 % group 1 , 90 % group 2A , 94 % group 2B ) . There were no significant differences in 5-year event-free survival ( EFS ) or in overall survival ( OS ) when the 3 groups were compared ( group 1 : EFS 50 % , OS 56 % ; group 2A : EFS 50 % , OS 60 % ; group 2B : EFS 34 % , OS 50 % ) . RI deaths result ing from treatment toxicity were low-2 % for group 1 and 5 % for group 2 . More gastrointestinal , pulmonary , and renal toxicity but fewer infections were observed in patients receiving idarubicin ( P < .001 , P = .04 , P = .03 , respectively ) . Following RI chemotherapy , all patients received 3 to 4 more courses of identical chemotherapy and then underwent either autologous ( n = 156 ) or an allogeneic bone marrow transplantation ( BMT ) ( n = 35 ) . OS was higher in allogeneic BMT patients than in autologous BMT patients ( 79 % vs 63 % ; P = .23 ) . We conclude that daunorubicin is as effective as idarubicin for remission-induction therapy for childhood AML and has reduced toxicity In the r and omized trial AML-BFM 93 we compared 60 mg/m2/day daunorubicin with 12 mg/m2/day idarubicin for 3 days each , combined with cytarabine and etoposide during induction . Results showed a significant better blast cell reduction in the bone marrow on day 15 in patients of the idarubicin arm ( 25 of 144 = 17 % of patients with ⩾5 % blasts compared to 46 of 149 = 31 % of patients after daunorubicin , Pχ2 = 0.01 ) . This was , however , mainly seen in high risk patients treated with idarubicin ( 19 % vs 38 % , Pχ2 = 0.007 ) . Cardiotoxicity , WHO grade 1–3 shortening fraction reduction after induction occurred in 6 % patients in both arms . Bone marrow toxicity differed slightly with a median recovery time of neutrophils > 500/μl of 25 days ( daunorubicin ) compared to 27 days ( idarubicin ) , P = 0.05 . In the total group of patients probabilities of 5 years event-free survival and disease-free survival were similar for patients treated with daunorubicin or idarubicin ( 49 % ± 4 % vs 55 % ± 4 % and 57 % ± 4 % vs 64 % ± 4 % , P logrank 0.29 and 0.15 , respectively ) . However , in patients presenting with more than 5 % blasts on day 15 there was a trend for a better outcome after treatment with idarubicin ( P logrank 0.06 ) . Together with the early effect seen for high risk patients these results indicate a better efficacy of idarubicin than of daunorubicin during induction with a similar rate of toxicity Most clinical trials for acute leukemia have reported results after 2‐3 years of follow‐up . Comparisons between the original data and longer‐term follow‐up data may be of interest , particularly with regard to promising new therapies From December 1987 to June 1992 , 251 patients aged 50–65 with de novo acute myelogenous leukaemia ( AML ) were recruited to a multi‐institutional r and omized clinical trial . Induction therapy consisted of Ara‐C ( 200 mg/m2 , continuous infusion , days 1–7 ) with either zorubicin ( ZRB ) ( 200 mg/m2 , i.v . , days 1–4 ) or idarubicin ( IDR ) ( 8 mg/m2 , i.v . , days 1–5 ) . Consolidation therapy consisted of a single course of intensive chemotherapy with high‐dose Ara‐C ( 3 g/m2 , 3 h infusion , q 12 h , days 1–4 ) and m‐Amsa ( 100 mg/m2/d , i.v . , days 5–7 ) Various regimens have been explored in the treatment of acute nonlymphoblastic leukaemia ( AML ) , but so far none has been shown to be superior . Here we report on a comparison of three widely used protocol s defined by Berman ( Group 1 ) , MRC AML 10 ( Group 2 ) , and Arlin ( Group 3 ) . Group 1 includes cytosine arabinoside ( Ara-C ) ( 100 mg/m2/d , days 1–7 ) and idarubicin ( Ida ) ( 12 mg/m2/d , days 1–3 ) for induction , and Ara-C ( 200 mg/m2/d , days 1–6 ) and Ida ( 15 mg/m2/d , day 1 ) twice for consolidation . Group 2 includes Ara-C ( 200 mg/m2/d , days 1–10 ) , daunorubicin ( Dnc ) ( 50 mg/m2/d , days 1 , 3 , 5 ) and etoposide ( VP16 ) ( 100 mg/m2/d , days 1–5 ) for induction . The first consolidation therapy consisted of the same schedule except for Ara-C given on days 1–8 . The second consolidation regimen consisted of Ara-C ( 200 mg/m2/d , days 1–8 ) , VP16 ( 100 mg/m2/d , days 1–5 ) and amsacrine ( 100 mg/m2/d , days 1–5 ) . Mitoxantrone ( Mitox ) ( 10 mg/m2/d , days 1–5 ) and Ara-C ( 200 mg/m2/d , days 1–3 ) were given as the third consolidation therapy . Group 3 was identical to Group 1 except for Ida being replaced with Mitox . During the study period 99 patients were enrolled and 34 were allocated r and omly to Group 1 , 36 to Group 2 , and 29 to Group 3 . Except for age distribution all patients ’ characteristics were similar between the groups . As there were more elderly patients in Group 1 , time to complete remission ( CR ) was longer in this group as they needed more second induction . Induction deaths were 9.7 % , 12.9 % and 14.8 % in Groups 1 , 2 and 3 , respectively . Patients in Group 2 received a higher amount of Ara-C compared with the other groups ( P<0.001 ) . After a median follow-up period of 45 months ( 1–67 for survivors ) an advantage in Group 1 was observed . Relapse-free survival ( RFS ) was better in Group 1 ( P=0.014 ) at 3 years . Fourteen of the patients were transplanted ( 11 allografts , 3 autografts ) . When patients with transplants were excluded , overall survival was longer in Group 1 both at 3 years and 5 years ( P=0.05 ) . In conclusion , despite patient advanced age and lower dose of Ara-C , the idarubicin-containing treatment was superior to the other regimens Until 1983 , results of treatment of acute myelogenous leukemia ( AML ) in Pol and with different regimens were very poor . In 1983 , the Polish Pediatric Leukemia/Lymphoma Study Group introduced a unified treatment protocol – a modified version of BFM-83 protocol . This led to an increase in the curability of AML from 15 % to approximately 32 % . In 1994 , a modification was made : the high-risk patients ( > 5 % blasts in bone marrow on day 15 of therapy and all M5 cases ) received two additional cycles with intermediate-dose cytarabine ( ID-ARAC ) . This led to a nonsignificant improvement in the 5-year event-free survival ( EFS ) rate from 32 to 36 % . A new treatment protocol employing idarubicin in place of daunorubicin was introduced in 1998 and produced better initial responses , increase in the number of patients attaining remission after induction therapy and proportional increase of st and ard-risk patients .The probability of 5-year EFS ( pEFS ) for the whole group of patients increased from 36 to 47 % . In st and ard- and high-risk groups , the 5-year pEFS was 62 and 33 % , respectively . The probability of 5-year disease-free survival was 58 % in the whole group , and there were no differences between risk groups . Unsatisfactory treatment results in children classified into the high-risk group are principally due to the low remission rate In previously untreated adult patients with acute non-lymphocytic leukemia ( ANLL ) , idarubicin ( IDA ) and daunorubicin ( DNR ) were compared for efficacy and safety when used in combination with cytarabine ( Ara-C ) . IDA 12 mg/m2/d and DNR 40 mg/m2/d were administered by intravenous ( i.v . ) bolus for 3 consecutive days ( days 1 to 3 ) , respectively , in combination with Ara-C 80 mg/m2 given by 2-hour i.v . infusion , every 12 hours for 7 consecutive days . The number of assessable patients was 32 for each group . The rate of complete remission ( CR ) was 59.4 % ( 19/32 ) in the IDA group and 40.6 % ( 13/32 ) in the DNR group . The clinical equivalence test with delta = 10 % demonstrated that the remission rate in the IDA group was equal or superior ( P = .010 ) to the DNR group . In addition , the Cochran-Mantel-Haenszel test for response means with scores of 3 ( CR ) , 2 ( partial response [ PR ] , and 1 ( no response [ NR ] ) showed the IDA group to be significantly superior ( P = .044 ) to the DNR group . The duration needed to attain less than 5 % leukemic cells in the bone marrow tended to be shorter in the IDA group ( P = .072 ) , and in CR patients , the number of days needed to reach the nadir value for leukemic cells was significantly fewer in the IDA group ( P = .037 ) . The nadir value for WBC count was significantly lower in the IDA group ( P = .022 ) . As for adverse reactions , high incidences of diarrhea and stomatitis were observed in the IDA group , while the incidences of other adverse reactions were similar between the two groups . When the effects of the drug on the ECG were examined , significant changes in ECG parameters were observed after treatment in the DNR group but not in the IDA group . Based on these findings , it was surmised that the combination of IDA plus Ara-C is the treatment of first choice for adult ANLL patients A total of 1111 children with acute myeloblastic leukaemia ( AML ) were treated in four consecutive Berlin – Frankfurt – Münster ( BFM ) studies from 1978 to 1998 . The first cooperative trial AML-BFM 78 established intensive chemotherapy with seven drugs , CNS irradiation and 2-year maintenance , achieving a long-term survival ( overall survival ( OS ) ) of 40 % . Induction intensification in AML-BFM 83 result ed in significant improvement of disease-free survival ( DFS ) . The risk of haemorrhage , especially in children with hyperleukocytosis , proved the high relevance of supportive care . In AML-BFM 87 , the benefit of CNS irradiation in preventing CNS/systemic relapses was demonstrated . In AML-BFM 93 , the introduction of idarubicin during first induction followed by intensification with HAM increased the 5-year EFS , DFS and OS to 50±2 , 61±3 and 57±2 % , respectively . Stem cell transplantation ( SCT ) , as applied in high-risk patients with a matched related donor , did not significantly improve the outcome compared to chemotherapy alone . In spite of treatment intensification , the therapy-related death rate decreased from trial to trial , mainly during induction . The future aim is to reduce long-term sequelae , especially cardiotoxicity , by administration of less cardiotoxic drugs , and toxicity of SCT by risk-adapted indications . The AML-BFM studies performed in three European countries with > 70 cooperating centres have significantly improved the outcome in AML children ; nevertheless , increasing experience with these intensive treatment regimens is of fundamental importance to reduce fatal complications To compare the antileukemic efficacy of idarubicin and mitoxantrone in elderly patients with acute myeloid leukemia ( AML ) and to evaluate the feasibility of autologous transplantation using PBSC after consolidation in those with a good performance status , 160 patients ( median age 69 years ) , with AML at diagnosis , 118 of them with de novo AML and 42 with AML secondary to myelodysplastic syndrome or toxic exposure ( sAML ) , received induction treatment with idarubicin , 8 mg/m2/day or mitoxantrone , 7 mg/m2/day , on days 1 , 3 , and 5 , both combined with VP-16 , 100 mg/m2/day on days 1 to 3 and cytarabine ( araC ) , 100 mg/m2/day , on days 1 to 7 . G-CSF , 5 μg/kg/day , was administered after chemotherapy in patients aged more than 70 years . Patients in complete remission ( CR ) received one course of consolidation using the same schedule as for induction except the araC administration was shortened to 5 days . Some patients younger than 70 years were then scheduled for autologous stem cell harvest on days 5 to 7 of G-CSF , 5 μg/kg/day , initiated after hematopoietic recovery from consolidation . Autologous transplantation was performed following an additional chemotherapy conditioning . Ninety-five patients ( 59 % ) achieved CR , without significant difference between the idarubicin ( 56 % CR ) and mitoxantrone ( 63 % CR ) group . There was also no significant difference in CR rate between de novo AML ( 63 % ) and secondary AML ( 55 % ) ( P = 0.12 ) . Patients aged < 70 years had 67 % cr , while patients aged ≥ 70 years had 49 % ( P = 0.02 ) . There was no significant difference in the duration of aplasia between the two arms . Median time to neutrophil recovery was 22 days in patients who received G-CSF following induction and 27 days in patients who did not ( P = 0.006 ) . Severe extra-hematologic toxicities of induction did not differ between the two arms and included sepsis ( 39 % ) , diarrhea ( 13 % ) , hyperbilirubinemia ( 8 % ) , hemorrhage ( 6 % ) and vomiting ( 6 % ) . Overall , 14 patients ( 9 % ) , died from toxicity of induction . First consolidation was administered in 74 patients of whom seven ( 9 % ) died from toxicity . Nineteen patients have received transplantation . Median time to recovery of neutrophils > 0.5 × 109/1 was 13 days and of platelets > 50 × 109/l 43 days following consolidation . There were two toxic deaths . Median disease-free survival and survival from time of achieving CR of non transplanted patients are 6 and 7 months respectively without difference between the two arms . Fourteen transplanted patients relapsed at a median of 5 months post-transplant . We conclude that this regimen is well tolerated and has a good efficacy to induce CR , without a significant difference in efficacy and toxicity between idarubicin and mitoxantrone . Intensive postinduction , including transplantation , is feasible ; however , this procedure did not seem to prevent early relapse in the majority of patients . Neither the high rate of CR nor consolidation nor transplant procedure in a selected group of patients did translate into improved DFS and /or survival Fifty-three patients of median age 66 years ( 39 patients > 60 yrs ) , including 5 with FAB unclassified or secondary acute myeloid leukemia ( AML ) at diagnosis , 14 with resistant AML , 19 in first and 15 in subsequent relapse , were treated with carboplatin ( CBP ) , 200 mg/m2/day , as a continuous infusion , ( days 3 to 7 ) with mitoxantrone ( MIT ) or idarubicin ( IDA ) , ( 12 mg/m2/day ) as an i.v . bolus , on days 1 to 3 . Results were evaluated after one induction course . Overall , 15 patients ( 28 % [ 95 % confidence interval ( CI ) , 17 - 42 % ] , 8/28 with IDA and 7/25 with MIT ) achieved complete remission ( CR ) . There was no statistical difference between IDA and MIT arms . Fourty-nine percent ( 95 % CI , 35 - 63 % ) had resistant disease ( 53 % IDA versus 44 % MIT respectively ) and 23 % ( 95 % CI , 12 - 36 % ) died from toxicity ( 18 % IDA versus 28 % MIT ) . Median duration s of neutrophils less than 0.5 x 10(9)/l and platelet counts less than 20 x 10(9)/l were 32 and 32 days respectively in the IDA arm and 31 and 26 days respectively in the MIT arm . Severe toxicity included infections ( 45 % ) , diarrhea ( 21 % ) , bleeding ( 9 % ) , vomiting ( 7 % ) , hyperbilirubinemia ( 6 % ) , mucositis ( 4 % ) ( no statistical difference was seen between both arms ) . Nephrotoxicity was observed in only one case in the IDA arm . Cardiac toxicity included reversible pulmonary oedema in one patient in the IDA arm . No severe ototoxicity was noted . CR patients received maintenance courses with 3 days of CBP and one day of IDA or MIT . Median survival was 2 months ( range , 1 - 30 + months ) and 2.5 months ( range , 0.5 - 19.5 months ) , and median disease-free survival ( DFS ) 2 months ( range , 1 - 30 + months ) and 2.5 months ( range , 1 - 14 months ) in the IDA and MIT arms respectively . We conclude that CBP at a cumulative dosage of 1 g/m2 together with intercalating agents ( IDA/MIT ) has antileukemic efficacy in elderly patients From March 1993 to October 1993 , 20 consecutive , newly diagnosed acute promyelocytic leukemia ( APL ) patients from 13 Italian institutions entered in a pilot study named AIDA , combining all-trans retinoic acid ( ATRA ) with idarubicin ( IDA ) . ATRA was administered orally beginning on the first day of induction at the dosage of 45 mg/m2/d until complete remission ( CR ) , whereas IDA was administered intravenously at the dosage of 12 mg/m2/d on days 2 , 4 , 6 , and 8 of the induction . Patients who achieved CR were consoli date d with 3 courses of chemotherapy without ATRA ; thereafter , they were followed up for molecular and hematologic CR . The median age was 35.3 years ( range , 6.5 to 67.6 years ) ; 8 patients were males and 12 females ; 4 had the hypogranular variant of APL ( M3v ) , and 4 ( 2 with M3v ) presented with leukocyte counts > or = 10,000/microL. Molecular analysis for the promyelocytic leukemia-retinoic acid receptor alpha ( PML-RAR alpha ) hybrid gene at diagnosis was performed in 16 patients by means of reverse transcription-polymerase chain reaction ( RT-PCR ) analysis , and all were RT-PCR+ for the hybrid gene . In the remaining 4 patients , the cytogenetic study showed the presence of the t(15;17 ) . After a median time of 36 days ( range , 28 to 52 days ) 18 ( 90 % ) patients achieved CR ; the remaining 2 patients died 12 and 34 days after diagnosis from myocardial infa rct ion caused by fungal myocarditis and from massive hemoptysis , respectively . ATRA syndrome was observed in only 2 patients , and , after the prompt discontinuation of ATRA and initiation of dexamethasone , both recovered from the syndrome . However , after recovering , 1 patient achieved CR , whereas the other died at day 34 because of massive hemoptysis ; other side effects were very limited . At recovery from the third consolidation course , only 3 of 14 ( 21.4 % ) tested patients were RT-PCR+ for the PML-RAR alpha hybrid gene . Of these , 2 relapsed shortly afterwards ; however , in the last patient , the PML-RAR alpha disappeared at successive testing performed 2 months later . As of September 30 , 1995 , after a median follow-up period from diagnosis of 27 months ( range , 24 to 31 months ) , the overall survival and event-free survival duration s are 85 % and 69 % , respectively ; moreover , 14 of 18 ( 78 % ) patients who achieved CR are still alive and in first molecular and hematologic CR . Of the 4 relapsed patients , 3 achieved a second CR with ATRA and , after further treatment , are now in molecular and hematologic CR after 4 + , 16 + , and 17 + months from the second CR . These results indicate that ( 1 ) the AIDA protocol is highly effective in treating APL ; ( 2 ) after 3 consolidation courses , the majority of patients who achieved CR are RT-PCR- for the hybrid gene PML-RAR alpha ; ( 3 ) the persistence of an RT-PCR positivity for the PML-RAR alpha hybrid gene after 3 consolidation courses is indicative of early relapse , thus these patients still require additional treatment . These results have prompted the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto ( GIMEMA ) to initiate , in cooperation with the Associazione Italiana di Ematologia ed Oncologia Pediatrica and some European Organization for Research and Treatment of Cancer ( EORTC ) centers , a new multicentric clinical trial named AIDA LAP 0493 for the treatment of adult and pediatric APL patients . All patients are considered eligible if APL diagnosis is confirmed with molecular or cytogenetic studies for PML-RAR alpha hybrid gene or t(15;17 ) and are enrolled to receive the same induction and consolidation therapy of this pilot study . After consolidation , patients who are RT-PCR- for PML-RAR alpha hybrid gene are r and omized to four arms , whereas patients who are RT-PCR+ after consolidation undergo , if eligible , an allogenic transplantation procedure PURPOSE A r and omized clinical trial was undertaken to compare the therapeutic effectiveness of idarubicin ( IDR ) to daunorubicin ( DNR ) , and both were given in combination with cytarabine ( CA ) in acute myelogenous leukemic ( AML ) patients . PATIENTS AND METHODS Newly diagnosed patients were given a daily infusion of CA ( 100 mg/m2 ) for 7 days and were assigned r and omly to receive DNR ( 45 mg/m2 ) or IDR ( 12 mg/m2 ) daily for the first 3 days . Those patients who achieved a complete remission ( CR ) were given three consolidation courses that consisted of CA ( 100 mg/m2 intravenously [ IV ] ) and thioguanine ( TG ; 100 mg/m2 orally ) every 12 hours for 5 days and either DNR ( 50 mg/m2 ) or IDR ( 15 mg/m2 ) on the first day of each cycle . After consolidation , patients received late intensification , which consisted of the same drugs used for induction except that the CA was given for 5 days and the anthracycline for 2 days . Four courses were planned at 13-week intervals . RESULTS The CR rates were 75 of 105 ( 71 % ) on the IDR arm and 65 of 113 ( 58 % ) on the DNR arm ( P = .03 ) . The median survival and median remission duration s were 297 and 433 days , respectively , on the IDR arm . The median survival and median remission duration s were 277 and 328 days , respectively , on the DNR arm . Six deaths occurred during late intensification , five on IDR and one on DNR ; this approach was ab and oned after 47 patients were entered . The median survival was significantly longer for patients who received late intensification . CONCLUSION This trial demonstrated that IDR was more effective than DNR in remission induction in AML A total of 120 patients with high-risk myelodysplastic syndrome ( MDS ) and AML progressed from MDS ( MDS – AML ) were registered in a r and omized controlled study of the Japan Adult Leukemia Study Group ( JALSG ) . Untreated adult patients with high-risk MDS and MDS – AML were r and omly assigned to receive either idarubicin and cytosine arabinoside ( IDR/Ara-C ) ( Group A ) or low-dose cytosine arabinoside and aclarubicin ( CA ) ( Group B ) . The remission rates were 64.7 % for Group A ( 33 of 51 evaluable cases ) and 43.9 % for Group B ( 29 out of 66 evaluable cases ) . The 2-year overall survival rates and disease-free survival rates were 28.1 and 26.0 % for Group A , and 32.1 and 24.8 % for Group B , respectively . The duration of CR was 320.6 days for Group A and 378.7 days for Group B. There were 15 patients who lived longer than 1,000 days after diagnosis : 6 and 9 patients in Groups A and B , respectively . However , among patients enrolled in this trial , intensive chemotherapy did not produce better survival than low-dose chemotherapy . In conclusion , it is necessary to introduce the first line therapy excluding the chemotherapy that can prolong survival in patients with high-risk MDS and MDS – AML A prospect i ve r and omized study was conducted comparing the efficacy and toxicity of two anthracyclines for the treatment of patients with acute myeloid leukemia ( AML ) between 55 and 75 years . A total of 220 patients were r and omized to receive as induction chemotherapy cytosine arabinoside ( Ara-C : 100 mg/m2/day ; continuous infusion for 7 days ) combined with either daunorubicin ( DNR : 50 mg/m2/day , i.v . bolus for 3 days ) ( n=108 ) or idarubicin ( IDA : 8 mg/m2/day , i.v . bolus for 5 days ) ( n=112 ) . The complete remission ( CR ) rate was similar ( P=0.296 ) after IDA ( 76/112 ; 68 % ) and DNR ( 66/108 ; 61 % ) ( P=0.3 ) . For patients aged 55 - 65 , the CR rate was significantly higher after IDA ( 39/47 ; 83 % ) than after DNR ( 29/50 ; 58 % ) ( P=0.007 ) . Persistent leukemia was more frequent after DNR ( 26/108 ) than after IDA ( 13/112 ; P=0.015 ) . Hematological and extra-hematological toxicities were similar . The CR patients were given a consolidation course of chemotherapy with Ara-C : 50 mg/m2/12 h , subcutaneously for 5 days , combined with either DNR:30 mg m2/day , i.v . bolus for 3 days or IDA:8 mg/m2/day i.v . bolus for 3 days according to the initial r and omization , and then received a continuous maintenance treatment for 2 years . The survival and disease-free survival ( DFS ) were similar in both groups ; there was no difference in the risk of relapse . However , there was a trend for a longer event-free survival ( EFS ) in the IDA group than for the DNR patients ( P=0.07 ) . Our results seem to indicate that IDA is probably more efficient than DNR for AML patients between 55 and 75 years , and confirm the data published in other studies comparing prospect ively IDA and DNR in adults The presented study compares the efficacy and the toxicity of idarubicine and mitoxantrone in combination with cytosar ( 3 + 7 ) in induction treatment of the patients with AML aged 55 - 75 . 31 patients at the age of 55 - 75 ( median 62 ) were evaluated in the arm with idarubicine and 29 patients at the age of 57 - 74 ( median 64 ) in the arm with mithoxantrone . Complete haematological remission was achieved in 13 patients ( 41.9 % ) in the arm with idarubicine and 15 patients ( 51.7 % ) in the arm with mitoxantrone . The medians of overall survival time ( OS ) and disease free survival time ( DFS ) were 22 and 44 weeks in the idarubicine arm and 35 and 40 weeks in the mitoxantrone arm , respectively . Statistical analysis did not prove any significant difference in the complete remission rates , in the number of deaths during cytopenia , in the OS or DFS , in the duration of hospitalisation , severe neutropenia and thrombopenia , in the number of days with febrile neutropenia , or in the consumption of platelets and erythrocytes transfusion units between both arms . Despite the fact that these results are not statistically significant in favour of any treatment arm , which is probably influenced also by the small number of evaluated patients , more favourable results were achieved in the arm with mithoxantrone with the respect to the evaluated parameters . From the point of view of cost-effectiveness , the difference could be observed when considering the price of both intercalating cytostatics . The use of mitoxantrone ( Refador , Lachema ) is 15x times cheaper per course of treatment than the use of idarubicine ( Zavedos , Pharmacia ) . Autologous peripheral blood stem cells transplantation ( APBSC ) was carried out only in 4 patients younger than 60 . No one of them was cured by APBSC but the median of OS of these patients was longer than the median in the other patients of the group . The results achieved are comparable with those of other trials conducted by various foreign groups . The possible causes of our unfavourable treatment results in this high-risk category of aged patients and the ways how to individualize the treatment with the use of prognostic factors analysis and how to improve the quality of life of the patients has been discussed We have studied the pharmacokinetics of idarubicin and daunorubicin in a total of 16 leukemic patients treated with one of these drugs associated with aracytine . The AUCs obtained for unchanged drugs were proportional to the dose , and the dose-independent pharmacokinetic parameters were very similar for the two drugs : total plasma clearance ( 39.0 L/h/m2 for idarubicin versus 38.6 for daunorubicin ) , total volume of distribution ( 1756 versus 1725 L/m2 ) and elimination half-life ( 42.7 versus 47.4 h ) . The only metabolites detected were the 13-dihydroderivative of each drug , idarubicinol or daunorubicinol . The elimination half-life of idarubicinol was two times higher than that of daunorubicinol ( 80.7 versus 37.3 h ) which provided an AUC ratio metabolite/parent drug higher for idarubicin than for daunorubicin . In view of the fact that idarubicinol is a much more active metabolite than daunorubicinol , this protracted half-life metabolite can account for the reported higher activity of idarubicin as compared to daunorubicin The cost-effectiveness of two chemotherapeutic regimens was evaluated from the results of a r and omized clinical trial involving patients with previously untreated acute myeloid leukemia . The evaluable subjects were 120 patients with acute myeloid leukemia r and omly assigned to receive 12 mg/m2 of idarubicin ( IDA ) or 50 mg/m2 of daunorubicin ( DNR ) daily for three days . The patients also received 200 mg/m2 of cytosine arabinoside daily for five days , with an additional 25-mg/m2 bolus on the first day of treatment , the patients underwent a second course at the same doses . The total hospital charges per patient were $ 59,687 for IDA treatment and $ 59,567 for DNR treatment ; however , the cost per complete remission was lower in the IDA than in the DNR patients ( $ 74,609 vs $ 102,115 ) . The lower remission rate in the DNR-treated patients , and thus their need for additional care , will increase the cost differences between the two treatments . The hospital charges per year of survival were $ 36,395 for IDA treatment and $ 52,714 for DNR treatment . It is concluded that IDA is more cost-effective than DNR in the treatment of adult acute myeloid leukemia A r and omized trial comparing idarubicin plus cytarabine ( IDA/Ara-C ) with doxorubicin plus cytarabine ( ADM/Ara-C ) in induction therapy for ANL , L was carried out . The IDA/Ara-C regimen consisted of idarubicin 20 mg/m(2 ) p.o . given on days 1 , 2 and 3 plus cytarabine 25 mg/m(2 ) as a loading dose followed by 100 mg/m(2 ) by continuous infusion daily × 7 days . The ADM/Ara-C regimen consisted of adriamycin 30 mg/m(2 ) on days 1 , 2 and 3 and the same dose of cytarabine . Patients who responded to the first cycle with at least 502 , reduction of marrow blasts received a second treatment cycle followed by a consolidation cycle of the same treatment for those in CR at the end of 2 cycles . 35/52 ( 6770 receiving ADM/Ara-C achieved CR , with 25 ( 48 % ) patients in CR after a single treatment cycle . 28/48 ( 58 % ) receiving ADM/Ara-C achieved CR of whom 11 ( 23 % ) went into remission after the first treatment cycle . IDA/Ara-C caused less nausea and vomiting , less stomatitis , a shorter duration of neutropenia and less need for platelet support than ADM/Ara-C. The median duration of CR is 62 weeks for IDA/Ara-C and 48 weeks for ADM/Ara.-C. These differences are not statistically significant . Clinical cardiotoxicity occurred in 4/48 patients treated with ADM/Ara-C. No clinical cardiac toxicity was observed in those receiving IDA/Ara-C. The mean post-treatment ejection fraction was , in addition , lower for ADM/Ara-C than for IDA/Ara-C. It is concluded that IDA/Ara-C is an effective and safe induction therapy for ANLL |
781 | 22,855,269 | Collectively , the available evidence indicates that , at commonly recommended doses , none of these herbs act as potent or moderate inhibitors or inducers of cytochrome P450 ( CYP ) enzymes or P-glycoprotein ( ABCB1 ) .
Weak effects in terms of either induction or inhibition were found for GB ( presystemic/hepatic CYP3A4 induction/inhibition , CYP2C19 induction at high doses ) , milk thistle/silymarin ( CYP2C9 inhibition ) , GS/berberine ( CYP3A4 and CYP2D6 inhibition ) , Echinacea ( presystemic/hepatic CYP3A4 inhibition/induction , CYP1A2 and CYP2C9 inhibition at high doses ) .
Information was found not always complete for the major drug metabolizing CYP enzymes in the less well-studied herbs and is largely limited to P-glycoprotein ( ABCB1 ) when effects on drug transporters have been investigated | The use of herbal/botanical products , also referred to as complementary and alternative medicines ( CAM ) , worldwide enjoys increasing popularity .
It appears in particular highly prevalent in patient population s already exposed to complex treatment algorithms and polypharmacotherapy , frequently involving narrow therapeutic index drugs .
Accordingly , the potential clinical dimension and relevance of herb-drug interactions has received considerable attention over the last years .
However , review of pertinent literature indicates that the available clinical evidence in this regard is still limited and sometimes inconclusive . | The effects of goldenseal ( Hydrastis canadensis ) and kava kava ( Piper methysticum ) supplementation on human CYP3A activity were evaluated using midazolam ( MDZ ) as a phenotypic probe . Sixteen healthy volunteers were r and omly assigned to receive either goldenseal or kava kava for 14 days . Each supplementation phase was followed by a 30‐day washout period . MDZ ( 8 mg , per os ) was administered before and after each phase , and pharmacokinetic parameters were determined using st and ard non‐compartmental methods . Comparisons of pre‐ and post‐supplementation MDZ pharmacokinetic parameters revealed significant inhibition of CYP3A by goldenseal ( AUC(0–∞ ) , 107.9±43.3 vs 175.3±74.8 ng·h/ml ; Cl/F/kg , 1.26±0.59 vs 0.81±0.45 l/h/kg ; T1/2 , 2.01±0.42 vs 3.15±1.12 h ; Cmax , 50.6±26.9 vs 71.2±50.5 ng/ml ) . MDZ disposition was not affected by kava kava supplementation . These findings suggest that significant herb – drug interactions may result from the concomitant ingestion of goldenseal and CYP3A substrates Phytochemical‐mediated modulation of cytochrome P450 ( CYP ) activity may underlie many herb‐drug interactions . Single‐time point phenotypic metabolic ratios were used to determine whether long‐term supplementation of Citrus aurantium , Echinacea purpurea , milk thistle ( Silybum marianum ) , or saw palmetto ( Serenoa repens ) extracts affected CYP1A2 , CYP2D6 , CYP2E1 , or CYP3A4 activity Phytochemical-mediated modulation of P-glycoprotein ( P-gp ) and other drug transporters may give rise to many herb-drug interactions . Serial plasma concentration-time profiles of the P-gp substrate , digoxin , were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo . Twenty healthy volunteers were r and omly assigned to receive a st and ardized goldenseal ( 3210 mg daily ) or kava kava ( 1227 mg daily ) supplement for 14 days , followed by a 30-day washout period . Subjects were also r and omized to receive rifampin ( 600 mg daily , 7 days ) and clarithromycin ( 1000 mg daily , 7 days ) as positive controls for P-gp induction and inhibition , respectively . Digoxin ( Lanoxin , 0.5 mg ) was administered p.o . before and at the end of each supplementation and control period . Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay . Comparisons of area under the curve (AUC)(0–3 ) , AUC(0–24 ) , Cmax , CL/F , and elimination half-life were used to assess the effects of goldenseal , kava kava , rifampin , and clarithromycin on digoxin pharmacokinetics . Rifampin produced significant reductions ( p < 0.01 ) in AUC(0–3 ) , AUC(0–24 ) , CL/F , t1/2 , and Cmax , whereas clarithromycin increased these parameters significantly ( p < 0.01 ) . With the exception of goldenseal 's effect on Cmax ( 14 % increase ) , no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava . When compared with rifampin and clarithromycin , supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics , suggesting that these supplements are not potent modulators of P-gp in vivo The effects of berberine ( BBR ) on the pharmacokinetics of ciclosporin A ( CsA ) were examined in healthy volunteers . Six healthy male volunteers were orally treated with 0.3 g BBR , twice daily for 10 days . Pharmacokinetic investigations on CsA at 6 mg/kg were done both before and at the end of the BBR treatment period . Another six healthy male volunteers were involved in the pharmacokinetic study with 3 mg CsA/kg , in which the subjects orally received the second single dose of 3 mg CsA/kg , followed by a single oral dose of 0.3 g BBR . The blood CsA concentrations were determined by fluorescence polarization immunoassay . In the pharmacokinetic study with 6 mg CsA/kg , BBR caused no significant changes in the pharmacokinetic parameters of CsA. However , in the trial with 3 mg CsA/kg , the average percentage increase in area under the blood concentration-time curve of CsA was 19.2 % ( P < 0.05 ) and the mean C12 increased to 123 microg/l from 104 microg/l ( P < 0.05 ) , without altering elimination half-life ( t(1/2 ) ) , maximum blood drug concentration ( Cmax ) , time to Cmax ( tmax ) , apparent oral clearance ( CL/F ) . The present results suggest that BBR can increase the oral bioavailability of CsA at the dosage of 3 mg/kg . The BBR-mediated increase in CsA bioavailability may be partly attributed to a decrease in liver and /or intestinal metabolism through the inhibition of CYP3A4 in the liver and /or gut wall . The BBR-induced increase in emptying time of stomach and small intestine might be another reason for the increase in CsA bioavailability . However , the speculation should be proved by further investigation Phytochemical-mediated modulation of P-glycoprotein ( P-gp ) and other drug transporters may underlie many herb-drug interactions . Serial serum concentration-time profiles of the P-gp substrate , digoxin , were used to determine whether supplementation with milk thistle or black cohosh modified P-gp activity in vivo . Sixteen healthy volunteers were r and omly assigned to receive a st and ardized milk thistle ( 900 mg daily ) or black cohosh ( 40 mg daily ) supplement for 14 days , followed by a 30-day washout period . Subjects were also r and omized to receive rifampin ( 600 mg daily , 7 days ) and clarithromycin ( 1000 mg daily , 7 days ) as positive controls for P-gp induction and inhibition , respectively . Digoxin ( Lanoxicaps , 0.4 mg ) was administered orally before and at the end of each supplementation and control period . Serial digoxin serum concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay . Comparisons of area under the serum concentration time curves from 0 to 3 h ( AUC(0–3 ) ) , AUC(0–24 ) , Cmax , apparent oral clearance of digoxin ( CL/F ) , and elimination half-life were used to assess the effects of milk thistle , black cohosh , rifampin , and clarithromycin on digoxin pharmacokinetics . Rifampin produced significant reductions ( p < 0.01 ) in AUC(0–3 ) , AUC(0–24 ) , and Cmax , whereas clarithromycin increased these parameters significantly ( p < 0.01 ) . Significant changes in digoxin half-life and CL/F were also observed with clarithromycin . No statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either milk thistle or black cohosh , although digoxin AUC(0–3 ) and AUC(0–24 ) approached significance ( p = 0.06 ) following milk thistle administration . When compared with rifampin and clarithromycin , supplementation with these specific formulations of milk thistle or black cohosh did not appear to affect digoxin pharmacokinetics , suggesting that these supplements are not potent modulators of P-gp in vivo Phytochemical‐mediated modulation of cytochrome P450 ( CYP ) activity may underlie many herb‐drug interactions . Single‐time point phenotypic metabolic ratios were used to determine whether long‐term supplementation of goldenseal ( Hydrastis canadensis ) , black cohosh ( Cimicifuga racemosa ) , kava kava ( Piper methysticum ) , or valerian ( Valeriana officinalis ) extracts affected CYP1A2 , CYP2D6 , CYP2E1 , or CYP3A4/5 activity Purpose We assessed the human in vivo metabolic drug interaction profile of Ginkgo biloba extract EGb 761 ® with respect to the activities of major cytochrome P450 ( CYP ) enzymes . Methods A single-center , open-label , r and omized , three-fold crossover , cocktail phenotyping design was applied . In r and om order , the following treatments were administered to 18 healthy men and women for 8 days each : placebo twice daily , EGb 761 ® 120 mg twice daily , and EGb 761 ® 240 mg in the morning and placebo in the evening . In the morning of day 8 , administration was performed together with the orally administered phenotyping cocktail ( enzyme , metric ) : 150 mg caffeine ( CYP1A2 , paraxanthine/caffeine plasma ratio 6-h postdose ) , 125 mg tolbutamide ( CYP2C9 , plasma concentration 24-h postdose ) , 20 mg omeprazole ( CYP2C19 , omeprazole/5-hydroxy omeprazole plasma ratio 3-h postdose ) , 30 mg dextromethorphan ( CYP2D6 , dextromethorphan/dextrorphan plasma ratio 3-h postdose ) , and 2 mg of midazolam ( CYP3A , plasma concentration 6-h postdose ) . Formally , absence of a relevant interaction was assumed if the 90 % confidence intervals ( CIs ) for EGb 761 ® /placebo ratios of the metrics were within the 0.70–1.43 range . Results EGb 761 ® /placebo ratios for phenotyping metrics were close to unity for all CYPs . Furthermore , respective CIs were within the specified margins for all ratios except CYP2C19 for EGb 761 ® 120 mg twice daily ( 90 % CI 0.681–1.122 ) and for CYP2D6 for EGb 761 ® 240 mg once daily ( 90 % CI 0.667–1.281 ) . These findings were attributed to the intraindividual variability of the metrics used . All treatments were well tolerated . Conclusion EGb 761 ® has no relevant effect on the in vivo activity of the major CYP enzymes in humans and therefore has no relevant potential to cause respective metabolic drug – drug interactions BACKGROUND & AIMS Ginkgo biloba extract ( EGb 761 ) has been shown to ameliorate some defects associated with the insulin resistance syndrome and so patients with Type 2 diabetes mellitus ( T2DM ) may be inclined to co-ingest the herb with their medications , such as metformin . This study was design ed to determine if the co-ingestion of EGb 761 and metformin would alter the pharmacokinetic properties of metformin in T2DM patients and persons without diabetes , who may ingest it for other purpose s. METHOD Normal glucose tolerance ( NGT ) subjects ( n=10 ; age , 39.2+/-14.0 years ; fasting plasma glucose ( FPG ) , 90+/-7 mg/dl ; body mass index ( BMI ) , 24.1+/-3.7 kg/m(2 ) ) and 10 T2DM patients ( n=10 ; age , 51.7+/-8.9 years ; FPG , 150+/-7 mg/dl ; BMI , 33.7+/-5.7 kg/m(2 ) ) completed a r and omized , double-blind , placebo-controlled crossover study . They ingested either EGb 761 ( 12 0mg/day as a single dose ) or a vegetable-based placebo during each arm for 3 months . At the end of each arm , the NGT subject ingested a single 500 mg dose of metformin ( non-diabetics ) and the T2DM subject took his/her prescribed metformin dose ( 250 - 850 mg ) with 120 mg EGb 761 . Blood and urine sample s were collected over an 8-h period , and in the case of T2DM subjects , additionally over the first 2h of the subsequent 3 days . RESULTS Ingestion of EGb 761 produced no significant changes in diagnostic laboratory tests in either group , except reducing glycosylated hemoglobin A(1c ) levels ( from 7.7+/-1.2 to 7.2+/-0.9 % , P<0.05 ) in T2DM the subjects . The pharmacokinetic parameters of metformin were all significantly different ( P<0.05 ) between the NGT ( 500 mg ) and 8 out of 10 of the T2DM subjects who were prescribed 500 mg of metformin during the placebo cycles . During the EGb 761 cycles , only the elimination half-life in the T2DM subjects was significantly increased ( 0.117+/-0.085 to 0.141+/-0.100 , P<0.05 ) . CONCLUSION The co-ingestion of 120 mg of EGb 761 and 500 mg of metformin did not significantly affect the pharmacokinetic properties of metformin . Further studies are required to verify this observation for smaller and larger dose of metformin with other doses of EGb 761 , since T2DM patients on medication constitute a very heterogeneous group ABSTRACT The aim of this open-label , fixed-sequence study was to investigate the potential of Echinacea purpurea , a commonly used botanical supplement , to interact with the boosted protease inhibitor darunavir-ritonavir . Fifteen HIV-infected patients receiving antiretroviral therapy including darunavir-ritonavir ( 600/100 mg twice daily ) for at least 4 weeks were included . E. purpurea root extract capsules were added to the antiretroviral treatment ( 500 mg every 6 h ) from days 1 to 14 . Darunavir concentrations in plasma were determined by high-performance liquid chromatography immediately before and 1 , 2 , 4 , 6 , 8 , 10 , and 12 h after a morning dose of darunavir-ritonavir on days 0 ( darunavir-ritonavir ) and 14 ( darunavir-ritonavir plus echinacea ) . Individual darunavir pharmacokinetic parameters were calculated by noncompartmental analysis and compared between days 0 and 14 with the geometric mean ratio ( GMR ) and its 90 % confidence interval ( CI ) . The median age was 49 ( range , 43 to 67 ) years , and the body mass index was 24.2 ( range , 18.7 to 27.5 ) kg/m2 . Echinacea was well tolerated , and all participants completed the study . The GMR for darunavir coadministered with echinacea relative to that for darunavir alone was 0.84 ( 90 % CI , 0.63 - 1.12 ) for the concentration at the end of the dosing interval , 0.90 ( 90 % CI , 0.74 - 1.10 ) for the area under the concentration-time curve from 0 to 12 h , and 0.98 ( 90 % CI , 0.82 - 1.16 ) for the maximum concentration . In summary , coadministration of E. purpurea with darunavir-ritonavir was safe and well tolerated . Individual patients did show a decrease in darunavir concentrations , although this did not affect the overall darunavir or ritonavir pharmacokinetics . Although no dose adjustment is required , monitoring darunavir concentrations on an individual basis may give reassurance in this setting Cytochrome P450 2D6 ( CYP2D6 ) , an important CYP isoform with regard to drug-drug interactions , accounts for the metabolism of approximately 30 % of all medications . To date , few studies have assessed the effects of botanical supplementation on human CYP2D6 activity in vivo . Six botanical extracts were evaluated in three separate studies ( two extracts per study ) , each incorporating 16 healthy volunteers ( eight females ) . Subjects were r and omized to receive a st and ardized botanical extract for 14 days on separate occasions . A 30-day washout period was interposed between each supplementation phase . In study 1 , subjects received milk thistle ( Silybum marianum ) and black cohosh ( Cimicifuga racemosa ) . In study 2 , kava kava ( Piper methysticum ) and goldenseal ( Hydrastis canadensis ) extracts were administered , and in study 3 subjects received St. John 's wort ( Hypericum perforatum ) and Echinacea ( Echinacea purpurea ) . The CYP2D6 substrate , debrisoquine ( 5 mg ) , was administered before and at the end of supplementation . Pre- and post-supplementation phenotypic trait measurements were determined for CYP2D6 using 8-h debrisoquine urinary recovery ratios ( DURR ) . Comparisons of pre- and post-supplementation DURR revealed significant inhibition ( approximately 50 % ) of CYP2D6 activity for goldenseal , but not for the other extracts . Accordingly , adverse herb-drug interactions may result with concomitant ingestion of goldenseal supplements and drugs that are CYP2D6 substrates Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections , diabetes , hypertension , and hypercholesterolemia . Many studies have reported interactions between berberine-containing products and cytochromes P450 ( CYPs ) , but little is known about whether berberine alters CYP activities in humans , especially after repeated doses . Methods A two-phase r and omized-crossover clinical study in healthy male subjects was performed . After 2 weeks of berberine ( 300 mg , t.i.d . , p.o . ) administration , midazolam , omeprazole , dextromethorphan , losartan , and caffeine were used to evaluate enzyme activities of CYP3A4 , 2C19 , 2D6 , 2C9 , and CYP1A2 , respectively . Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold ( P < 0.01 ) . In addition , losartan/E-3174 ratio doubled ( P < 0.01 ) after BBR administration , indicating a decrease in CYP2C9 activity . CYP3A4 activity was also inhibited , as the Cmax , AUC0–∞ , and AUC0–12 of midazolam were increased 38 % ( P < 0.05 ) , 40 % ( P < 0.01 ) , and 37 % ( P < 0.05 ) after BBR treatment , respectively . Compared with the placebo period , the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h , respectively ; the oral clearance of midazolam was decreased 27 % ( P < 0.05 ) ; and the phenotypic indices of 1 h midazolam/1′-hydroxymidazolam increased 59 % ( P < 0.01 ) . There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group . Conclusions Repeated administration of berberine ( 300 mg , t.i.d . , p.o . ) decreased CYP2D6 , 2C9 , and CYP3A4 activities . Drug-drug interactions should be considered when berberine is administered CONTEXT Data on the range of prescription and over-the-counter drug use in the United States are not available . OBJECTIVE To provide recent population -based information on use of all medications , including prescription and over-the-counter drugs , vitamins and minerals , and herbal preparations/natural supplements in the United States . DESIGN , SETTING , AND PARTICIPANTS Ongoing telephone survey of a r and om sample of the noninstitutionalized US population in the 48 continental states and the District of Columbia ; data analyzed here were collected from February 1998 through December 1999 . MAIN OUTCOME MEASURE Use of medications , by type , during the preceding week , compared by demographic characteristics . RESULTS Among 2590 participants aged at least 18 years , 81 % used at least 1 medication in the preceding week ; 50 % took at least 1 prescription drug ; and 7 % took 5 or more . The highest overall prevalence of medication use was among women aged at least 65 years , of whom 12 % took at least 10 medications and 23 % took at least 5 prescription drugs . Herbals/supplements were taken by 14 % of the population . Among prescription drug users , 16 % also took an herbal/supplement ; the rate of concurrent use was highest for fluoxetine users , at 22 % . Reasons for drug use varied widely , with hypertension and headache mentioned most often ( 9 % for each ) . Vitamins/minerals were frequently used for nonspecific reasons such as " health " ( 35 % ) ; herbals/supplements were also most commonly used for " health " ( 16 % ) . CONCLUSIONS In any given week , most US adults take at least 1 medication , and many take multiple agents . The substantial overlap between use of prescription medications and herbals/supplements raises concern about unintended interactions . Documentation of usage patterns can provide a basis for improving the safety of medication use Ticlopidine is sometimes coadministered with ergoloid mesylates or ginkgo biloba in clinical situations . Our objective was to examine the effect of ergoloid mesylates and ginkgo biloba on ticlopidine pharmacokinetics . Ticlopidine , ergoloid mesylates , and ginkgo biloba significantly inhibited the organic anion transporting polypeptide (OATP-B)-mediated uptake of [(3)H]-estrone-3-sulfate in a concentration-dependent manner . When ergoloid mesylates was coadministered with ticlopidine , the ticlopidine area under the plasma drug concentration-time profile ( AUC ) from 0 to 12 hours was decreased 30 % and the peak plasma drug concentration ( C(max ) ) was decreased 29 % , compared with ticlopidine administration alone . There were no significant changes in the pharmacokinetic parameters of ticlopidine when it was coadministered with ginkgo biloba . In summary , ergoloid mesylates is a more potent inhibitor of OATP-B than is ginkgo biloba , and it can reduce the oral bioavailability of drugs transported by OATP-B. Ergoloid mesylates markedly decreased the AUC and C(max ) of ticlopidine , probably by inhibiting the OATP-B-mediated uptake of ticlopidine during the intestinal absorption phase . The results support a new model of intestinal drug-drug interaction Objective To study the effects of berberine ( BBR ) on the blood concentration and pharmacokinetics of cyclosporin A ( CsA ) in renal-transplant recipients . Methods In a r and omized and controlled clinical trial , 52 renal-transplant recipients were treated with CsA and 0.2 g BBR three times daily for 3 months , while another 52 subjects received CsA without BBR co-administration . Blood trough concentration of CsA and biochemistry indexes for hepatic and renal functions were determined . For the pharmacokinetic study , six renal-transplant recipients were included with a 3-mg/kg dosage of CsA twice daily before and after oral co-administration of 0.2 g BBR three times daily for 12 days . Results The trough blood concentrations and the ratios of concentration/dose of CsA in the BBR-treated group increased by 88.9 % and 98.4 % , respectively , compared with those at baseline ( P<0.05 ) . As for the BBR-free group , they rose by 64.5 % and 69.4 % , respectively , relative to those at baseline ( P<0.01 ) . Nevertheless , the final blood concentrations and the ratios of concentration/dose of CsA in BBR-treated patients were still 29.3 % and 27.8 % , respectively , higher than those in BBR-free patients ( P<0.05 ) . No significant effects on liver or renal functions were observed under coadministration of BBR . After co-administration of BBR in six patients for 12 days , the mean AUC of CsA was increased by 34.5 % ( P<0.05 ) . The mean time taken to reach the peak blood concentration ( tmax ) and the mean half-life ( t1/2 ) of CsA were increased by 1.7 h and 2.7 h , respectively ( P<0.05 ) . The average percentage increases in the steady-state drug concentration ( Css ) and minimum blood concentration ( Cmin ) were 34.5 % and 88.3 % , respectively ( P<0.05 ) . In addition , the average percentage decrease in CL/F was 40.4 % ( P<0.05 ) and the peak-to-through fluctuation index was significantly reduced ( P<0.01 ) . Conclusion The BBR can markedly elevate the blood concentration of CsA in renal-transplant recipients in both clinical and pharmacokinetic studies . This combination may allow a reduction of the CsA dosage . The mechanism for this interaction is most likely explained by inhibition of CYP3A4 by BBR in the liver and /or small intestine UNLABELLED M : The aim of this study was to investigate the effect of St John 's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin . METHODS This was an open-label , three-way crossover r and omized study in 12 healthy male subjects , who received a single 25-mg dose of warfarin alone or after 14 days ' pretreatment with St John 's wort , or 7 days ' pretreatment with ginseng . Dosing with St John 's wort or ginseng was continued for 7 days after administration of the warfarin dose . Platelet aggregation , international normalized ratio ( INR ) of prothrombin time , warfarin enantiomer protein binding , warfarin enantiomer concentrations in plasma and S-7-hydroxywarfarin concentration in urine were measured . Statistical comparisons were made using anova and 90 % confidence intervals are reported . RESULTS INR and platelet aggregation were not affected by treatment with St John 's wort or ginseng . The apparent clearances of S-warfarin after warfarin alone or with St John 's wort or ginseng were , respectively , 198 + /- 38 ml h(-1 ) , 270 + /- 44 ml h(-1 ) and 220 + /- 29 ml h(-1 ) . The respective apparent clearances of R-warfarin were 110 + /- 25 ml h(-1 ) , 142 + /- 29 ml h(-1 ) and 119 + /- 20 ml h(-1 ) [ corrected ] . The mean ratio and 90 % confidence interval ( CI ) of apparent clearance for S-warfarin was 1.29 ( 1.16 , 1.46 ) and for R-warfarin it was 1.23 ( 1.11 , 1.37 ) when St John 's wort was coadministered . The mean ratio and 90 % CI of AUC(0 - 168 ) of INR was 0.79 ( 0.70 , 0.95 ) when St John 's wort was coadministered . St John 's wort and ginseng did not affect the apparent volumes of distribution or protein binding of warfarin enantiomers . CONCLUSIONS St John 's wort significantly induced the apparent clearance of both S-warfarin and R-warfarin , which in turn result ed in a significant reduction in the pharmacological effect of rac-warfarin . Coadministration of warfarin with ginseng did not affect the pharmacokinetics or pharmacodynamics of either S-warfarin or R-warfarin STUDY OBJECTIVE To characterize the pharmacokinetics of indinavir in the presence and absence of milk thistle and to determine the offset of any effect of milk thistle on indinavir disposition . DESIGN Prospect i ve open-label drug interaction study . SETTING Outpatient clinic . SUBJECTS Ten healthy volunteers . Intervention . Blood sample s were collected over 8 hours after the volunteers took four doses of indinavir 800 mg every 8 hours on an empty stomach for baseline pharmacokinetics . This dosing and sampling were repeated after the subjects took milk thistle 175 mg ( confirmed to contain silymarin 153 mg , the active ingredient ) 3 times/day for 3 weeks . After an 11-day washout , indinavir dosing and blood sampling were repeated to evaluate the offset of any potential interaction . MEASUREMENTS AND MAIN RESULTS Indinavir concentrations were measured by using a vali date d high-performance liquid chromatography method . The following pharmacokinetic parameters were determined : highest concentration ( Cmax ) , hour-0 concentration , hour-8 concentration ( C8 ) , time to reach Cmax , and area under the plasma concentration-time curve over the 8-hour dosing interval ( AUC8 ) . Milk thistle did not alter significantly the overall exposure of indinavir , as evidence d by a 9 % reduction in the indinavir AUC8 after 3 weeks of dosing with milk thistle , although the least squares mean trough level ( C8 ) was significantly decreased by 25 % . CONCLUSION Milk thistle in commonly administered dosages should not interfere with indinavir therapy in patients infected with the human immunodeficiency virus The effect of Ginkgo biloba on the activity of CYP2C9 , the isoform responsible for S-warfarin clearance , was assessed in 11 healthy volunteers who received single 100-mg doses of flurbiprofen , a probe substrate for CYP2C9 . Subjects also received either a st and ardized G biloba leaf preparation ( Ginkgold , 3 doses of 120 mg ) or matching placebo in a r and omized , double-blind , 2-way crossover study . Mean kinetic variables for flurbiprofen with either placebo or G biloba were elimination half-life , 3.9 versus 3.5 hours ; total AUC , 57 versus 55 microg/mL h ; and oral clearance , 32.9 versus 31.6 mL/min . None of these differences was significant . Based on highperformance liquid chromatography analysis , each 60-mg Ginkgold tablet contained 6.6 mug of amentoflavone and 61.2 microg of quercetin , both previously identified as CYP2C9 inhibitors . These amounts were apparently too low to inhibit CYP2C9 function in vivo . The results confirm previous controlled clinical studies showing no effect of ginkgo on the kinetics or dynamics of warfarin Objectives To evaluate the effect of silymarin on the pharmacokinetics of rosuvastatin in systems overexpressing OATP1B1 or BCRP transporters and in healthy subjects . Material s and Methods The concentration-dependent transport of rosuvastatin and the inhibitory effect of silymarin were examined in vitro in OATP1B1-expressing oocytes and MDCKII-BCRP cells . For in vivo assessment , eight healthy male volunteers , divided into two groups , were r and omly assigned to receive placebo or silymarin ( 140 mg ) three times per day for 5 days . On day 4 , all subjects received rosuvastatin ( 10 mg , 8 am ) 1 h after the placebo or silymarin administration . A series of blood sample s were collected for 72 h , and the plasma concentration of rosuvastatin was determined using LC-MS/MS . Results Based on the concentration dependency of rosuvastatin transport in the OATP1B1 and BCRP overexpression systems , rosuvastatin is a substrate for both transporters . Silymarin inhibited both OATP1B1- and BCRP-mediated rosuvastatin transport in vitro ( Ki 0.93 μM and 97 μM , respectively ) . However , no significant changes in AUC , half-life , Vd/F , or Cl/F of rosuvastatin were observed in human subjects following pretreatment with silymarin . Conclusions Silymarin does not appear to affect rosuvastatin pharmacokinetics in vivo , suggesting that silymarin , administered according to a recommended supplementation regimen , is not a potent modulator of OATP1B1 or BCRP in vivo The objective of this study was to investigate the effect of concomitantly administered silymarin on the pharmacokinetics of talinolol , a typical substrate for P-glycoprotein ( P-gp ) , in healthy Chinese volunteers and its association with a multidrug resistance 1 ( MDR1 ) C3435 T genetic polymorphism . Eighteen healthy adult men ( six MDR1 3435CC homozygotes , six MDR1 3435CT heterozygotes and six MDR1 3435TT homozygotes ) were recruited in a two-phase , r and omized , single-blind , crossover design . The pharmacokinetics of talinolol were measured after co-administration of placebo or 140 mg silymarin capsules three times daily for 14 days . Concentrations of talinolol in plasma were measured for up to 36 h after drug administration by liquid chromatography-mass spectrometry ( HPLC-MS ) . The peak plasma concentration ( Cmax ) of talinolol was significantly higher after silymarin administration as compared with placebo ( p = 0.007 ) . The area under the plasma concentration – time curve from zero to 36 h ( AUC0–36 ) and AUC0–∞ of talinolol was increased by 36.2 % ± 33.2 % and 36.5 % ± 37.9 % , respectively , by silymarin co-administration . The oral clearance ( CL/F ) of talinolol was decreased by 23.1 % ± 16.6 % ( p < 0.001 ) during the silymarin-treated phase . No change in the time to peak concentration ( tmax ) and the blood elimination half-life ( t1/2 ) of talinolol was observed between the placebo- and silymarin-treated phases . Co-administration of silymarin significantly increased the plasma concentration of talinolol in healthy volunteers Concomitant administration of botanical supplements with drugs that are P-glycoprotein ( P-gp ) substrates may produce clinical ly significant herb-drug interactions . This study evaluated the effects of St. John 's wort and Echinacea on the pharmacokinetics of digoxin , a recognized P-gp substrate . Eighteen healthy volunteers were r and omly assigned to receive a st and ardized St. John 's wort ( 300 mg three times daily ) or Echinacea ( 267 mg three times daily ) supplement for 14 days , followed by a 30-day washout period . Subjects were also r and omized to receive rifampin ( 300 mg twice daily , 7 days ) and clarithromycin ( 500 mg twice daily , 7 days ) as positive controls for P-gp induction and inhibition , respectively . Digoxin ( Lanoxin 0.25 mg ) was administered orally before and after each supplementation and control period . Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay . Comparisons of area under the curve (AUC)((0 - 3 ) ) , AUC((0 - 24 ) ) , elimination half-life , and maximum serum concentration were used to assess the effects of St. John 's wort , Echinacea , rifampin , and clarithromycin on digoxin disposition . St. John 's wort and rifampin both produced significant reductions ( p < 0.05 ) in AUC((0 - 3 ) ) , AUC((0 - 24 ) ) , and C(max ) , while clarithromycin increased these parameters significantly ( p < 0.05 ) . Echinacea supplementation did not affect digoxin pharmacokinetics . Clinical ly significant P-gp-mediated herb-drug interactions are more likely to occur with St. John 's wort than with Echinacea AIMS This study investigated the pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects . METHODS This was an open-label , r and omized , three-treatment , cross-over , clinical trial in healthy male subjects ( n= 12 ) of known CYP2C9 and VKORC1 genotype who received a single oral dose of warfarin alone or after 2 weeks of pre-treatment with each herbal medicine at recommended doses . Pharmacodynamic ( INR , platelet activity ) and pharmacokinetic ( warfarin enantiomer concentrations ) end points were evaluated . RESULTS The apparent clearance of (S)-warfarin ( 90 % CI of ratio ; 1.01 , 1.18 ) was significantly higher during concomitant treatment with echinacea but this did not lead to a clinical ly significant change in INR ( 90 % CI of AUC of INR ; 0.91 , 1.31 ) . Policosanol did not significantly affect warfarin enantiomer pharmacokinetics or warfarin response . Neither echinacea nor policosanol had a significant effect on platelet aggregation after 2 weeks of pre-treatment with the respective herbal medicines . CONCLUSION Echinacea significantly reduced plasma concentrations of S-warfarin . However , neither echinacea nor policosanol significantly affected warfarin pharmacodynamics , platelet aggregation or baseline clotting status in healthy subjects Human immunodeficiency virus (HIV)-infected patients often take herbal medicines , which may interact with antiretrovirals . American ginseng induces phase 2 and antioxidant enzymes in vitro and might increase the clearance of zidovudine and /or enhance antioxidant activity . Ten healthy volunteers received 300 mg of zidovudine orally before and after 2 weeks of treatment with a ginsenoside-enriched American ginseng extract 200 mg twice daily . This ginseng extract induced the phase 2 enzyme quinone reductase with an average concentration of doubling of enzyme activity of 190 microg/mL. Total ginsenoside content was 8.5 + /- 0.5 % . Pharmacokinetic profiles of zidovudine and oxidative stress marker concentrations were measured post-zidovudine dose . American ginseng does not significantly affect the formation clearance of zidovudine to its glucuronide ( ratio post- to pre-American ginseng = 1.17 ; 90 % confidence interval : 0.95 - 1.45 ; P = .21 ) , total clearance ( ratio = 0.97 ; 0.82 - 1.14 ; P = .70 ) , or plasma zidovudine AUC0 - 8 ( ratio = 1.03 ; 0.87 - 1.21 ; P = .77 ) . Oxidative stress biomarkers are reduced post-American ginseng ( F2-isoprostane ratio = 0.79 ; 0.72 - 0.86 ; P < .001 ; 8-hydroxy-deoxyguanosine ratio = 0.74 ; 0.59 - 0.92 ; P = .02 ) . Two weeks of American ginseng does not alter zidovudine pharmacokinetics but reduces oxidative stress markers This study was undertaken to clarify the influence of repeated oral administration of Ginkgo biloba extract ( GBE ) on CYP2C9 and CYP3A4 . CYP2C9 probe ( tolbutamide , 125 mg ) and CYP3A4 probe ( midazolam , 8 mg ) were orally administered to 10 male healthy volunteers before and after GBE intake ( 360 mg/d ) for 28 days , and they received 75 g glucose after the dosing of tolbutamide . Plasma drug concentrations and blood glucose levels were measured . The area under concentration versus time curve ( AUC0-infinity ) for tolbutamide after GBE intake was slightly but significantly ( 16 % ) lower than that before GBE intake . Concomitantly , GBE tended to attenuate AUC0 - 2 of blood glucose-lowering effect of tolbutamide . AUC0-infinity for midazolam was significantly ( 25 % ) increased by GBE intake and oral clearance was significantly ( 26 % ) decreased . Thus , it is suggested that the combination of GBE and drugs should be cautious in terms of the potential interactions , especially in elderly patients or patients treated with drugs exerting relatively narrow therapeutic windows Context Consuming ginseng , a commonly used herbal dietary supplement , has been associated with a decrease in warfarin 's anticoagulant effect in at least 1 case report . Contribution Healthy volunteers took warfarin with and without concurrently taking ginseng . Ginseng consumption lowered the international normalized ratio and decreased plasma warfarin levels . Caution s Patients and physicians should be aware that ginseng is among many substances that can interfere with warfarin 's anticoagulant effect . The Editors The beneficial effects of several commonly used botanicals have been documented ( 1 ) , but data on the safety of these herbs are limited . At least 16 % of people using prescription medication concurrently take herbal supplements . An estimated 15 million Americans are at risk for herbdrug interactions ( 2 ) . Advocated for almost every purpose , including maintaining general health , combating fatigue , and improving immune function ( 3 ) , ginseng is one of the best-selling herbs in the United States ( 4 ) . Herbs such as ginseng may interact with medications that have a narrow therapeutic index , such as warfarin , a commonly used oral anticoagulant ( 5 , 6 ) . A widely cited case report showed a substantial decrease in the anticoagulant effect of warfarin after ginseng consumption in a patient who was previously maintained with stable warfarin therapy ( 7 ) . We conducted a r and omized , double-blind , placebo-controlled trial to evaluate the potential interactions between American ginseng and warfarin . Methods Patients Nine men and 11 nonpregnant women ( who were paid $ 250 after trial completion ) were enrolled in this study . Patients were screened with a medical history , physical examination , 12-lead resting electrocardiography , complete blood and platelet counts , international normalized ratio ( INR ) ( the prothrombin time testcontrol ratio ) ( 8) , blood chemistry tests , and urinalysis . Patients agreed to abstain from tobacco products for at least 2 weeks before and during the study , abstain from alcohol and other medications during the study , and limit caffeine-containing products for 48 hours before and during the study . Protocol The institutional review board approved this 4-week study conducted at the University of Chicago Medical Center , Chicago , Illinois . All patients provided written , informed consent . Patients received oral warfarin , 5 mg daily , for the first 3 consecutive days during week 1 . Beginning in week 2 , patients were r and omly assigned to receive either oral American ginseng , 1.0 g , or placebo , twice daily , for 3 consecutive weeks . During week 4 , all patients again received oral warfarin , 5 mg daily , for the first 3 consecutive days ( Appendix Figure ) . Ginseng or placebo assignment was determined by a table of r and om numbers with blocks of 8 ( 4 ginseng and 4 placebo assignments per block ) , from which sealed , opaque envelopes were prepared and opened sequentially as patients were enrolled in the study . A biostatistician who did not acquire data prepared the assignments . Patients and investigators were blinded to the treatment groups . Patients were instructed to eat a balanced diet to maintain a consistent amount of vitamin K and to avoid drastic changes in dietary habits . The daily intake of vitamin Kcontaining foods was recorded 1 week before the study to obtain the baseline value and to adjust the diet if vitamin K intake was high . Patients recorded their daily diet throughout the study period , completed a written weekly question naire , and were asked to report any adverse events . Blood sample s were obtained at the same time ( 0.5 hour ) on days 1 , 3 , 4 , 5 , and 7 of weeks 1 and 4 to measure INR and plasma warfarin levels ( detection limit , 0.1 g/mL ) . Study Drugs Warfarin ( 3-(-acetonylbenzyl)-4-hydroxycoumarin or Coumadin , DuPont Pharmaceuticals , Wilmington , Delaware ) is a racemic mixture composed of equal amounts of 2 optical isomers . In our laboratory , we ground the root of American ginseng ( Panax quinquefolius , Wisconsin Ginseng Board , Wausau , Wisconsin ) from 1 lot into a fine powder and placed 0.5 g in nontransparent capsules . Using a high-performance liquid chromatography method , we found that the total ginsenoside content was 5.19 % . The constituent split was as follows : ginsenoside Rb1 , 1.93 % ; Rb2 , 0.20 % ; Rc , 0.61 % ; Rd , 0.42 % ; Re , 1.68 % ; and Rg1 , 0.35 % . We prepared identical placebo capsules that contained cornstarch powder . Statistical Analysis The primary end point of this study was the change in peak INR ( week 4 week 1 ) . Additional analysis end points were change in INR area under the curve ( AUC ) ( week 4 week 1 ) , defined as the area under the INR versus time curve ; change in peak plasma warfarin level ; change in warfarin AUC ( week 4 week 1 ) , defined as the area under the plasma warfarin level versus time curve ; and weekly vitamin K intake . The AUC was calculated on the basis of the trapezoidal rule by using measurements for days 1 through 7 . We compared changes in peak INR , INR AUC , peak plasma warfarin level , and warfarin AUC between the ginseng and placebo groups by using the Wilcoxon rank-sum test . We calculated the difference in median changes between the 2 groups and corresponding 95 % CIs according to the method described by Holl and er and Wolfe ( 9 ) , which is based on consideration of all pairwise differences between the 2 sets of observations . We calculated the Spearman rank correlation coefficients to examine the correlation between the change in peak INR and change in peak plasma warfarin levels . Repeated- measures analysis of variance ( ANOVA ) models were used to test differences in vitamin K intake between the groups and over time . A P value less than 0.05 was considered statistically significant . Stata , version 8 ( Stata Corp. , College Station , Texas ) , and Minitab , version 13 ( Minitab , Inc. , State College , Pennsylvania ) , were used for statistical analysis . Role of the Funding Sources The funding sources had no role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results Data from all 20 patients ( 12 patients in the ginseng group and 8 patients in the placebo group ) were used in the analysis . For the 6 men and 6 women in the ginseng group ( 7 patients were white , 3 patients were black , 1 patient was Hispanic , and 1 patient was Asian ) , the mean age and body weight ( SD ) were 30.2 7.2 years and 69.220.6 kg , respectively . For the 3 men and 5 women in the placebo group ( 3 patients were white , 2 patients were black , 2 patients were Hispanic , and 1 patient was Asian ) , the mean age and body weight ( SD ) were 24.3 4.0 years and 62.09.1 kg , respectively ( Appendix Table ) . In both groups , INR generally reached peak levels on day 4 after 3 consecutive days of warfarin administration . The Figure shows changes in individual peak INR , INR AUC , peak plasma warfarin level , and warfarin AUC from weeks 1 to 4 . The modest reduction in INR magnitude in the ginseng group was statistically significant compared with the change in the placebo group ( P= 0.0012 ) . Changes in INR AUC , peak plasma warfarin level , and warfarin AUC were also statistically significantly greater in the ginseng group . The Table summarizes results for the primary and secondary end points . Figure . Changes in individual peak international normalized ratio ( INR ) , INR area under the curve ( AUC ) , peak plasma warfarin level , and warfarin AUC in weeks 1 and 4 in American ginseng or placebo groups . A. P B. P C. P D. P Appendix Figure . Study flow chart showing American ginseng and placebo dosing and blood sample collection . Table . Changes in Peak International Normalized Ratio , International Normalized Ratio Area under the Curve , Peak Plasma Warfarin Level , and Warfarin Area under the Curve between Weeks 1 and 4 in American Ginseng and Placebo Groups Appendix Table . Patient Information For both peak warfarin level and AUC , the changes in the placebo group were not statistically significant and therefore probably reflected r and om variation in the small sample size . The Spearman rank correlation coefficient between changes in peak INR values and changes in peak warfarin levels was 0.72 ( P < 0.001 ) . One patient ( patient 18 ) in the ginseng group had a high baseline INR ( 1.32 ) on day 1 compared with that in the other patients ( mean INR [ SD ] , 0.94 0.04 ) . For this patient , peak INR after warfarin administration on day 4 was 5.16 . After ginseng administration , the peak INR was 2.75 and the corresponding AUC decreased from 17.46 to 11.1 . The patient 's peak plasma warfarin level also decreased from 1.6 g/mL during week 1 to 0.9 g/mL in week 4 . If this patient is excluded from the analysis , the results remain statistically significant . No unusual medical or drug history or diet was noted for this patient . For weeks 1 , 2 , 3 , and 4 , average daily vitamin K intake ( SD ) for the ginseng group was 32.3 5.2 g/d , 42.6 7.6 g/d , 41.9 8.6 g/d , and 34.0 5.5 g/d , respectively . The average daily vitamin K intake ( SD ) for the placebo group for weeks 1 , 2 , 3 , and 4 was 36.4 11.2 g/d , 32.0 8.4 g/d , 39.5 8.7 g/d , and 38.6 11.4 g/d , respectively . Vitamin K intake did not statistically significantly differ between the 2 groups ( P > 0.2 ) or over time ( P > 0.2 ) . No adverse effects of clinical importance occurred in this study . Discussion Among the several different species of ginseng , the major active components are ginsenosides , which are a diverse group of steroidal saponins ( 3 ) . Ginseng may promote bleeding in surgical patients ( 6 ) . Ginsenosides prolonged both thrombin time and activated partial thromboplastin time in rats ( 10 ) and inhibited platelet aggregation in vitro in human platelets ( 11 ) . In our healthy patients , however , ginseng reduced the anticoagulant effect of warfarin . We selected the commonly consumed American ginseng and a dose at the high end of the recommended range ( 12 ) . Warfarin indirectly interferes with blood clotting by depressing the hepatic synthesis of vitamin Kdependent coagulation factors . The Background Ginkgo biloba extract ( GBE ) , the best selling herbal medicine in the world , has been reported to inhibit P-glycoprotein in vitro . However , the effects of GBE on P-glycoprotein activity in humans have not been clarified . Objective To investigate the effects of single and repeated GBE ingestion on the oral pharmacokinetics of talinolol , a substrate drug for P-glycoprotein in humans . Methods Ten unrelated healthy male volunteers were selected to participate in a 3-stage sequential study . Plasma concentrations of talinolol from 0 to 24 hours were measured by high-performance liquid chromatography after talinolol 100 mg was administrated alone , with a single oral dose of GBE ( 120 mg ) , and after 14 days of repeated GBE ingestion ( 360 mg/day ) . Results A single oral dose of GBE did not affect the pharmacokinetics of talinolol . Repeated ingestion of GBE increased the talinolol maximum plasma concentration ( Cmax ) by 36 % ( 90 % CI 10 to 68 ; p = 0.025 ) , the area under the concentration-time curve (AUC)0 - 24 by 26 % ( 90 % CI 11 to 43 ; p = 0.008 ) and AUC0-∞ by 22 % ( 90 % CI 8 to 37 ; p = 0.014 ) , respectively , without significant changes in elimination half-life and the time to Cmax . Conclusions Our results suggest that long-term use of GBE significantly influenced talinolol disposition in humans , likely by affecting the activity of P-glycoprotein and /or other drug transporters Phytochemical-mediated modulation of cytochrome P450 enzymes ( CYPs ) may underlie many herb-drug interactions . This study 's purpose was to assess the effects of milk thistle and black cohosh supplementation on CYP3A activity and compare them to a clinical ly recognized inducer , rifampin , and inhibitor , clarithromycin . Healthy volunteers were r and omly assigned to receive a st and ardized milk thistle ( 900 mg ) or black cohosh ( 80 mg ) supplement for 14 days . Subjects also received rifampin ( 600 mg ) and clarithromycin ( 1000 mg ) for 7 days as positive controls for CYP3A induction and inhibition , respectively . Midazolam was administered orally before and after each supplementation and control period . The effects of milk thistle , black cohosh , rifampin , and clarithromycin on midazolam pharmacokinetics were determined using noncompartmental techniques . Unlike those observed for rifampin and clarithromycin , midazolam pharmacokinetics was unaffected by milk thistle or black cohosh . Milk thistle and black cohosh appear to have no clinical ly relevant effect on CYP3A activity in vivo Many medications are known to alter digoxin pharmacokinetics , including the herbal medication St. John 's wort . An open-labeled , r and omized , crossover trial was conducted in eight healthy human volunteers to determine if ginkgo biloba ( GB ) also alters the pharmacokinetics of digoxin . On two occasions separated by 2 weeks , subjects ingested digoxin , 0.5 mg . One week prior to each study phase , half of the volunteers were r and omly initiated on GB therapy , 80 mg three times daily , that continued until the end of the study phase . Immediately prior to and for 36 hours following digoxin ingestion , multiple blood sample s were collected for digoxin plasma concentration determination . No significant difference between treatments was observed with respect to AUC0−∞ ( digoxin alone : 21.0 ± 8.6 [ ng/mL ] × h ; digoxin + GB : 25.6 ± 13.2 [ ng/mL ] × h ) . Additionally , no significant difference between therapies was observed with respect to Cmax , Tmax , or Clo . In six subjects , ke and t1/2 were able to be determined . These parameters also did not differ significantly between treatments . In conclusion , within the context of the specific GB product used during this investigation , the concomitant use of GB and digoxin did not appear to have any significant effect on the pharmacokinetics of orally administered digoxin in healthy volunteers Siberian ginseng ( [ SG ] ; Eleutherococcus senticosus ) is a commonly used herbal preparation . The objective of this study was to assess in normal volunteers ( n = 12 ) the influence of a st and ardized SG extract on the activity of cytochrome P450 CYP2D6 and 3A4 . Probe substrates dextromethorphan ( CYP2D6 activity ) and alprazolam ( CYP3A4 activity ) were administered orally at baseline and again following treatment with SG ( 1 x 485 mg twice daily ) for 14 days . Urinary concentrations of dextromethorphan and dextorphan were quantified , and dextromethorphan metabolic ratios ( DMRs ) were determined at baseline and after SG treatment . Likewise , plasma sample s were collected ( 0 - 60 h ) for alprazolam pharmacokinetics at baseline and after SG treatment to assess effects on CYP3A4 activity . Vali date d high performance liquid chromatography methods were used to quantify all compounds and relevant metabolites . There were no statistically significant differences between pre- and post-SG treatment DMRs indicating a lack of effect on CYP2D6 ( P > 0.05 ) . For alprazolam there also were no significant differences in the pharmacokinetic parameters determined by noncompartmental modeling ( C(max ) , T(max ) , area under the curve , half-life of elimination ) indicating that SG does not significantly induce or inhibit CYP3A4 ( P > 0.05 ) . Our results indicate that st and ardized extracts of SG at generally recommended doses for over-the-counter use are unlikely to alter the disposition of coadministered medications primarily dependent on the CYP2D6 or CYP3A4 pathways for elimination To determine if soy extract or Panax ginseng increases the urinary excretion of the 6-beta-hydroxycortisol/cortisol ratio as a marker of cytochrome P450 ( CYP ) 3A enzyme induction , subjects received a soy extract containing 50 mg isoflavones twice daily ( n = 20 ) or Panax ginseng 100 mg st and ardized to 4 % ginsenosides twice daily ( n = 20 ) for 14 days . Neither Panax ginseng nor soy extract significantly altered the urinary 6-beta-OH-cortisol/cortisol ratio , suggesting that unlike St. John 's wort , they are not CYP3A inducers . Studies in vitro using human liver microsomes were performed to determine the effect of soy extract on probe substrates of CYP and UDP glucuronosyltransferase ( UGT ) . Unhydrolyzed soy extract produced very little inhibition of CYP1A2 , CYP2A6 , and CYP2D6 and a trend of activation of CYP3A4 . Hydrolyzed soy extract showed inhibition of all of the CYPs tested , particularly CYP2C9 and CYP3A4 . UGT2B15 was the only UGT significantly inhibited . Even though both soy extract and ginseng have been shown to activate CYP3A4 in vitro , there is a lack of an in vitro correlation with the in vivo effects Considerable interpatient variability in indinavir pharmacokinetics , possibly due in part to variable metabolism of the drug through intestinal cytochrome P450 ( CYP ) 3A4 , may contribute to poor virologic response in certain individuals with HIV infection . The purpose of this study was to characterize the influence of intestinal CYP3A4 modulation with grapefruit juice and Seville orange juice on indinavir pharmacokinetics . In an open-label , three-period crossover study , 13 healthy volunteers received indinavir 800 mg every 8 hours for 1 day and a single 800 mg dose the next morning . The last two indinavir doses were taken with 8 ounces of Seville orange juice , single-strength grapefruit juice , or water ( control ) . Plasma sample s were collected at time 0 ( predose ) and at 0.5 , 1 , 2 , 3 , 4 , and 5 hours after the last indinavir dose . Concentration-time data were analyzed using noncompartmental methods . Coadministration of Seville orange juice and indinavir result ed in a statistically significant increase in indinavir t(max ) ( 1.87 [ 1.65 - 2.22 ] vs. 1.25 [ 1.03 - 1.60 ] h ; p < 0.05 ) without altering other pharmacokinetic parameter values . Grapefruit juice administration did not result in any changes in indinavir pharmacokinetics . Modulation of intestinal CYP3A4 by grapefruit juice and Seville orange juice did not alter the systemic availability of indinavir . The contribution of presystemic metabolism to indinavir interpatient variability appears to be small BACKGROUND Ginkgo biloba extract is an herbal medicine used in the treatment of vascular disorders that may be coadministered with antiplatelet agents such as ticlopidine . Regulatory authorities requested evaluation of the pharmacodynamic and pharmacokinetic interactions between these entities , according to the drug-development guidance for fixed-dose combination formulations in Korea . OBJECTIVE This study was performed to evaluate the potential pharmacodynamic and pharmacokinetic interactions between ticlopidine and Ginkgo biloba extract . METHODS An open-label , r and omized , 2-period , 2-treatment , 2-sequence , single-dose crossover study was conducted in healthy Korean male volunteers . All volunteers were r and omly assigned to a sequence group for the 2 treatments , which consisted of ticlopidine 250 mg alone and ticlopidine 250 mg with Ginkgo biloba extract 80 mg , separated by a 1-week washout period between the treatments . Bleeding time was determined just before dosing and at 5 , 12 , and 48 hours after dosing . Platelet aggregation was evaluated before dosing and at 4 , 8 , 26 , and 48 hours after dosing . Blood sample s ( 8 mL ) from each of the volunteers were collected from an indwelling intravenous cannula inserted into a forearm vein before dosing and at 0.5 , 1 , 1.5 , 2 , 2.5 , 3 , 4 , 6 , 8 , 12 , 24 , and 48 hours after dosing . Ticlopidine concentrations were determined by a vali date d method using HPLC and ultraviolet detection . Adverse events were identified using general health-related questions , vital signs , physical examinations , ECGs , and laboratory tests . RESULTS A total of 24 healthy men participated in the study ( mean [ SD ] age , 24.1 [ 4.3 ] years ; weight , 66.6 [ 7.4 ] kg ; height , 174.7 [ 5.0 ] cm ) . The baseline corrected bleeding times were not significantly different between the ticlopidine-alone and ticlopidine/ Ginkgo biloba groups , and changes in platelet aggregation were not significantly different between the groups . Likewise , the pharmacokinetic parameters of ticlopidine were not significantly different between the groups ; the geometric mean ratios of the ticlopidine/ Ginkgo biloba group to the ticlopidine-alone group were 1.03 ( 90 % CI , 0.92 - 1.16 ) for C(max ) , 1.08 ( 90 % CI , 0.98 - 1.19 ) for AUC(0-last ) , and 1.10 ( 90 % CI , 1.00 - 1.20 ) for AUC(0-infinity ) . A total of 28 adverse events were reported : 11 in the ticlopidine-alone group and 17 in the ticlopidine/Ginkgo biloba group . The adverse events judged to be possibly related to ticlopidine in the ticlopidine-alone group were epigastric discomfort ( 2 cases ) , diarrhea ( 1 ) , skin eruption ( 1 ) , and a feeling of being cold ( 1 ) or hot ( 1 ) . The adverse events judged to be related to ticlopidine or Ginkgo biloba in the ticlopidine/Ginkgo biloba group were epigastric discomfort ( 2 ) , diarrhea ( 2 ) , nausea ( 2 ) , and headache ( 1 ) . CONCLUSIONS In this small group of healthy Korean men , the addition of a single dose of Ginkgo biloba extract did not prolong the bleeding time and was not associated with additional antiplatelet effects compared with the administration of ticlopidine alone . The coadministration of Ginkgo biloba extract with ticlopidine was not associated with any significant changes in the pharmacokinetic profile of ticlopidine compared with ticlopidine administered alone AIMS To evaluate the effect of acute dosing of garlic supplements on the single-dose pharmacokinetics of ritonavir . METHODS Ten healthy volunteers ( five male , five female ) were equally r and omized in a crossover design to receive 400 mg of a single dose of ritonavir within 10 min after eating breakfast either alone or with 10 mg of Natural Source Odourless Garlic . They received a total of eight doses of garlic extract ( 2 x 5 mg capsules ) taken twice daily for 4 days . Ritonavir and the seventh garlic dose were administered simultaneously . RESULTS Coadministration of garlic nonsignificantly decreased area under the plasma concentration-time curve ( AUC(0 , infinity ) ) by -17 % ( 90 % confidence interval ( CI ) , -31 % to 0 % ; range -46 % to 68 % ) and peak plasma concentration of ritonavir by -1 % ( 90 % CI , -25 % to 31 % ; range -51 % to 136 % ) . CONCLUSIONS Acute dosing of the garlic capsules over 4 days did not significantly alter the single-dose pharmacokinetics of ritonavir in healthy volunteers . Given the complex effects of both ritonavir and garlic on drug metabolism , the results of our study should not be extrapolated to steady-state conditions , where the possibility of an interaction still needs to be evaluated Saquinavir is an HIV proteinase inhibitor marketed as a treatment for HIV infection . The drug has potent ( Ki ∼ 0.1 nM ) antiviral activity and acts by inhibiting the processing of gag and gagpol polyproteins , thus blocking the maturation of replicated viral particles . By assuming st and ard two-compartment disposition kinetics in combination with a variety of absorption processes we have identified two structural models that perform well with respect to describing the pharmacokinetic behavior of saquinavir when administered to healthy human volunteers from various Phase I studies . These structural models have been implemented for population analysis of these Phase I data via the Bayesian Markov chain Monte Carlo approach . We conclude that saquinavir exhibits complex and highly variable behavior , but can be modeled adequately using a two-compartment zero-order absorption model . There is also an indication that saquinavir kinetics may be time-dependent St and ardized extracts from the Ginkgo biloba tree are purported to exert positive neurocognitive effects and may also be useful in the treatment of a variety of vascular and other disorders . This dietary supplement is among the most commonly used herbal preparations in the world . The objective of this study was to assess in normal volunteers ( n = 12 ) the influence of st and ardized Ginkgo biloba ( GB ) on the activity of cytochrome P-450 ( CYP ) 2D6 and 3A4 normal volunteers phenotyped as CYP2D6 extensive metabolizers . Probe substrates dextromethorphan ( CYP2D6 activity ) and alprazolam ( CYP 3A4 activity ) were co-administered orally at baseline , and following treatment with GB ( 120 mg twice daily ) for 14 days . Urinary concentrations of dextromethorphan and dextrorphan were quantified and dextromethorphan metabolic ratios ( DMRs ) were determined at baseline and after GB treatment . Likewise , plasma sample s were collected ( 0–60 hrs ) for alprazolam pharmacokinetics at baseline and after GB treatment to assess effects on CYP 3A4 activity . Vali date d HPLC methods were used to quantify all compounds and relevant metabolites . No statistically significant differences were found between baseline and post-GB treatment DMRs indicating a lack of effect on CYP2D6 . For alprazolam there was a 17 % decrease in the area under the plasma concentration versus time curve ( AUC ) ; ( P < 0.05 ) . However , the half-life of elimination was not significantly different after GB administration indicating a lack of hepatic CYP3A4 induction . We conclude that st and ardized extracts of GB at recommended doses are unlikely to significantly alter the disposition of co-administered medications primarily dependent on the CYP2D6 or CYP3A4 pathways for elimination OBJECTIVE Animal and in vitro data suggest that Ginkgo biloba extract ( GBE ) may modulate CYP3A4 activity . As such , GBE may alter the exposure of HIV protease inhibitors metabolized by CYP3A4 . It is also possible that GBE could alter protease inhibitor pharmacokinetics ( PK ) secondary to modulation of P-glycoprotein ( P-gp ) . The primary objective of the study was to evaluate the effect of GBE on the exposure of lopinavir in healthy volunteers administered lopinavir/ritonavir . Secondary objectives were to compare ritonavir exposure pre- and post-GBE , and assess the effect of GBE on single doses of probe drugs midazolam and fexofenadine . METHODS This open-label study evaluated the effect of 2 weeks of st and ardized GBE administration on the steady-state exposure of lopinavir and ritonavir in 14 healthy volunteers administered lopinavir/ritonavir to steady-state . In addition , single oral doses of probe drugs midazolam and fexofenadine were administered prior to and after 4 weeks of GBE ( following washout of lopinavir/ritonavir ) to assess the influence of GBE on CYP3A and P-gp activity , respectively . RESULTS Lopinavir , ritonavir and fexofenadine exposures were not significantly affected by GBE administration . However , GBE decreased midazolam AUC(0-infinity ) and C(max ) by 34 % ( p = 0.03 ) and 31 % ( p = 0.03 ) , respectively , relative to baseline . In general , lopinavir/ritonavir and GBE were well tolerated . Abnormal laboratory results included mild elevations in hepatic enzymes , cholesterol and triglycerides , and mild-to-moderate increases in total bilirubin . CONCLUSIONS Our results suggest that GBE induces CYP3A metabolism , as assessed by a decrease in midazolam concentrations . However , there was no change in the exposure of lopinavir , likely due to ritonavir 's potent inhibition of CYP3A4 . Thus , GBE appears unlikely to reduce the exposure of ritonavir-boosted protease inhibitors , while concentrations of unboosted protease inhibitors may be affected . Limitations to our study include the single sequence design and the evaluation of a ritonavir-boosted protease inhibitor exclusively Phytochemical‐mediated modulation of cytochrome P450 ( CYP ) activity may underlie many herb‐drug interactions . Single‐time point phenotypic metabolic ratios were used to determine whether long‐term supplementation of St John 's wort , garlic oil , Panax ginseng , and Ginkgo biloba affected CYP1A2 , CYP2D6 , CYP2E1 , or CYP3A4 activity AIM The aim of this study was to investigate the effect of two common herbal medicines , ginkgo and ginger , on the pharmacokinetics and pharmacodynamics of warfarin and the independent effect of these herbs on clotting status . METHODS This was an open label , three-way crossover r and omized study in 12 healthy male subjects , who received a single 25 mg dose of warfarin alone or after 7 days pretreatment with recommended doses of ginkgo or ginger from herbal medicine products of known quality . Dosing with ginkgo or ginger was continued for 7 days after administration of the warfarin dose . Platelet aggregation , international normalized ratio ( INR ) of prothrombin time , warfarin enantiomer protein binding , warfarin enantiomer concentrations in plasma and S-7-hydroxywarfarin concentration in urine were measured . Statistical comparisons were made using anova and the 90 % confidence intervals ( CIs ) of the ratio of log transformed parameters are reported . RESULTS INR and platelet aggregation were not affected by administration of ginkgo or ginger alone . The mean ( 95 % CI ) apparent clearances of S-warfarin after warfarin alone , with ginkgo or ginger were 189 ( 167 - 210 ) ml h(-1 ) , 200 ( 173 - 227 ) ml h(-1 ) and 201 ( 171 - 231 ) ml h(-1 ) , respectively . The respective apparent clearances of R-warfarin were 127 ( 106 - 149 ) ml h(-1 ) , 126 ( 111 - 141 ) ml h(-1 ) and 131 ( 106 - 156 ) ml h(-1 ) . The mean ratio ( 90 % CI ) of apparent clearance for S-warfarin was 1.05 ( 0.98 - 1.21 ) and for R-warfarin was 1.00 ( 0.93 - 1.08 ) when coadministered with ginkgo . The mean ratio ( 90 % CI ) of AUC(0 - 168 ) of INR was 0.93 ( 0.81 - 1.05 ) when coadministered with ginkgo . The mean ratio ( 90 % CI ) of apparent clearance for S-warfarin was 1.05 ( 0.97 - 1.13 ) and for R-warfarin was 1.02 ( 0.95 - 1.10 ) when coadministered with ginger . The mean ratio ( 90 % CI ) of AUC(0 - 168 ) of INR was 1.01 ( 0.93 - 1.15 ) when coadministered with ginger . The mean ratio ( 90 % CI ) for S-7-hydroxywarfarin urinary excretion rate was 1.07 ( 0.85 - 1.32 ) for ginkgo treatment , and 1.00 ( 0.81 - 1.23 ) for ginger coadministration suggesting these herbs did not affect CYP2C9 activity . Ginkgo and ginger did not affect the apparent volumes of distribution or protein binding of either S-warfarin or R-warfarin . CONCLUSIONS Ginkgo and ginger at recommended doses do not significantly affect clotting status , the pharmacokinetics or pharmacodynamics of warfarin in healthy subjects Garlic ( Allium sativum L. ) is a commonly used food and herbal supplement . The objective of this study was to assess in healthy volunteers ( N = 14 ) the influence of a garlic extract on the activity of cytochrome P450 ( CYP ) 2D6 and 3A4 . Probe substrates dextromethorphan ( CYP2D6 ) and alprazolam ( CYP3A4 ) were administered orally at baseline and again after treatment with garlic extract ( 3 × 600 mg twice daily ) for 14 days . Urinary dextromethorphan/dextrorphan ratios and alprazolam plasma concentrations were determined by HPLC at baseline and after garlic extract treatment . The ratio of dextromethorphan to its metabolite was 0.044 ± 0.48 at baseline and 0.052 ± 0.095 after garlic supplementation . There were no significant differences between the baseline and garlic phases ( P ≥ .05 ) . For alprazolam , there were no significant differences in pharmacokinetic parameters at baseline and after garlic extract treatment ( all P values ≥ .05 ; maximum concentration in plasma , 27.3 ± 2.6 ng/mL versus 27.3 ± 4.8 ng/mL ; time to reach maximum concentration in plasma , 1.9 ± 1.4 h versus 2.4 ± 1.8 h ; area under the time‐versus‐concentration curve , 537 ± 94 h · ng · mL−1 versus 548 ± 159 h · ng · mL−1 ; half‐life of elimination , 13.7 ± 4.4 h versus 14.5 ± 4.3 h ) . Our results indicate that garlic extracts are unlikely to alter the disposition of coadministered medications primarily dependent on the CYP2D6 or CYP3A4 pathway of metabolism STUDY OBJECTIVE To determine if milk thistle ( silymarin ) alters the pharmacokinetics of indinavir . DESIGN Sequential crossover trial . SETTING General clinical research center . SUBJECTS Ten healthy subjects . INTERVENTION Indinavir 800 mg 3 times/day was given for four doses on days 1 and 2 . Silymarin 160 mg 3 times/day was given on days 3 - 15 . On day 16 and for one dose on day 17 , both drugs were given at the same dosages . MEASUREMENTS AND MAIN RESULTS Indinavir 's pharmacokinetic parameters were evaluated at steady state both before and after administration of 14 days of silymarin . Blood sample s were collected -0.25 , 0.5 , 1 , 2 , 3 , 4 , and 5 hours after indinavir dosing and assayed by high-performance liquid chromatography . The final pharmacokinetic model had first-order absorption after a lag time , and two compartments with first-order elimination from the central compartment . When given alone and combined with silymarin , respectively , the geometric mean ( 95 % confidence interval [ CI ] ) steady-state indinavir area under the plasma concentration-time curve was 20.7 hr x mg/L ( 15.3 - 28.2 hr x mg/L ) and 19.4 hr x mg/L ( 15.8 - 23.6 hr x mg/L ) and the trough plasma concentration was 0.340 mg/L ( 0.232 - 0.497 mg/L ) and 0.232 mg/L ( 0.129 - 0.419 mg/L ) . CONCLUSION Silymarin has no apparent effect on indinavir plasma concentrations Ginkgo biloba extract is one of the most widely used herbal products in the United States . However , bleeding episodes in patients taking Ginkgo biloba and warfarin have been documented . Therefore , in vitro and in vivo inhibition studies were done to ascertain the influence of ginkgo on CYP2C9 , the P-450 isozyme responsible for the metabolism of the most potent warfarin enantiomer , (S)-warfarin . Ginkgo extract inhibited human liver microsomal CYP2C9 with an apparent Ki = 14.8 μg/mL , and the inhibition was increased by acid hydrolysis ( apparent Ki = 9.1 μg/mL ) . Two open-label , crossover pharmacokinetic studies in healthy subjects were performed using tolbutamide and diclofenac as probe CYP2C9 substrates . In contrast to the in vitro inhibition of CYP2C9 , no interactions between Ginkgo biloba extract and CYP2C9 probe substrates were observed in vivo as evidence d by the lack of effect on the steady-state pharmacokinetics of diclofenac or on the urinary metabolic ratio of tolbutamide |
782 | 32,274,586 | Compared with the OD/MD , results of this meta- analysis suggest that PELD has a lower risk of overall complications and a lower risk of complications necessitating conservative treatment . | This meta- analysis aims to compare the complication rates of discectomy/microdiscectomy ( OD/MD ) , microendoscopic discectomy ( MED ) , percutaneous endoscopic lumbar discectomy ( PELD ) , percutaneous laser disc decompression ( PLDD ) , and tubular discectomy for symptomatic lumbar disc herniation ( LDH ) using general classification and modified Clavien – Dindo classification ( MCDC ) schemes . | BACKGROUND : Transmuscular tubular diskectomy has been introduced to increase the rate of recovery , although evidence is lacking . OBJECTIVE : To evaluate the 2-year results of tubular diskectomy compared with conventional microdiskectomy . METHODS : Three hundred twenty-eight patients with persistent leg pain caused by lumbar disk herniation were r and omly assigned to undergo tubular diskectomy ( 167 patients ) or conventional microdiskectomy ( 161 patients ) . Main outcome measures were scores from Rol and -Morris Disability Question naire for Sciatica , Visual Analog Scale for leg pain and low-back pain , and Likert self-rating scale of global perceived recovery . RESULTS : On the basis of intention-to-treat analysis , there was no significant difference between tubular diskectomy and conventional microdiskectomy in Rol and -Morris Disability Question naire for Sciatica scores during 2 years after surgery ( between-group mean difference [ Δ ] = 0.6 ; 95 % confidence interval [ CI ] , −0.3 - 1.6 ) . Patients treated with tubular diskectomy reported more leg pain ( Δ = 3.3 mm ; 95 % CI , 0.2 - 6.2 ) and more low-back pain ( Δ = 3.0 mm ; 95 % CI , −0.2 - 6.3 ) than those patients treated with conventional microdiskectomy . At 2 years , 71 % of patients assigned to tubular diskectomy documented a good recovery vs 77 % of patients assigned to conventional microdiskectomy ( odds ratio , 0.76 ; 95 % CI , 0.45 - 1.28 ; P = .35 ) . Repeated surgery rates within 2 years after tubular diskectomy and conventional microdiskectomy were 15 % and 10 % , respectively ( P = .22 ) . CONCLUSION : Tubular diskectomy and conventional microdiskectomy result ed in similar functional and clinical outcomes . Patients treated with tubular diskectomy reported more leg pain and low-back pain , although the differences were small and not clinical ly relevant Objective Percutaneous endoscopic lumbar discectomy ( PELD ) and microdiscectomy with the microscope endoscopic tubular retractor system(METRx-MD ) are considered popular minimally invasive surgery ( MIS ) methods for the treatment of lumbar disc herniation . Many authors have also reported good clinical outcomes of these methods , but there are few comparative studies of them . This report compares the clinical outcomes of PELD and METRx-MD for lumbar disc herniation as MIS methods and discusses the efficacy of PELD . Methods Seventy-two patients who had undergone single-level unilateral discectomy using two different methods , PELD and METRx-MD , between 2009 and 2011 were given a follow-up examination prospect ively . Thirty-seven of these patients underwent discectomy using PELD , and the remaining 35 patients underwent discectomy using METRx-MD . In addition to the general parameters , clinical outcomes were assessed as specific parameters using the Visual Analogue Scale ( VAS ) score , the Oswestry Disability Index ( ODI ) , the Short-form 36 ( SF-36 ) , and the return-to-work time . Results Sixty-seven percent ( 25/37 ) of the patients in the PELD group and 74%(26/35 ) in the METRx-MD group were included in follow-up more than 6 months post-operatively . The mean improvements in the VAS scores for the back pain , leg pain , and ODI were 2.6 , 4.8 , and 30.1 % for the PELD group and 2.8 , 4.6 , and 33.2 % for the METRx-MD group , respectively . The SF-36 physical health component subscale score improved from 40.6 pre-operatively to 68.3 at the last follow-up for the PELD group post-operatively , and from 48.5 to 65.1 in the mental component subscale ( METRx-MD group : from 34.4 to 66.5 and from 44.87 to 56.7 ) . Complications occurred in 3/37 patients in the PELD group and in 2/35 patients in the METRx-MD group in the peri-operative period . The mean return-to-work times were 37.5 days in the PELD group and 42.5 days in the METRx-MD group . Conclusion The outcomes for the PELD group are comparable to those for the METRx-MD group . It can thus be concluded that PELD for lumbar disk herniations may be performed safely and effectively . Also , PELD can be considered one of the treatment modalities of lumbar disk herniation Background : Highly migrated intracanal disk herniation is not among the exclusion criteria of the interlaminar microendoscopic diskectomy ( MED ) procedure . The goal of this prospect i ve , r and omized , controlled study was to compare the effect of the size of the skin incision and the method of h and ling the multifidus muscle on the results of the interlaminar MED procedure versus conventional microdiskectomy in retrieving highly migrated intracanal disk herniations . Methods : Seventy-three patients with highly migrated intracanal lumbar disk herniations treated with either minimal incision , multifidus-sparing MED or conventional microdiskectomy were observed for 2 years . Primary ( clinical ) outcomes data included the results of the Numerical Rating Scale ( NRS ) for back and leg pain and the Oswestry Disability Index ( ODI ) to quantify pain and disability , respectively . Secondary objective outcomes data included surgical time , blood loss , postoperative analgesics , length of hospital stay , time to return to work , the rates of revision surgery complications , and the results of the patient satisfaction index ( PSI ) and the modified MacNab criteria . Results : At final follow-up , relief of leg pain was statistically significant for both groups . NRS back pain , ODI , PSI , and the modified MacNab criteria showed no improvement in the conventional microdiskectomy group . Secondary outcomes data in the MED group were significantly better than those for the control group . Conclusions : Highly migrated intracanal lumbar disk herniations can be sufficiently retrieved using minimal incision , multifidus-sparing MED , which is an effective alternative to conventional microdiskectomy . The minimal skin incision and multifidus-sparing approach of the MED had a positive effect on clinical outcomes , which were stable throughout the 2-year follow-up period . Level of Evidence : Therapeutic level In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Study Design . Prospect i ve , r and omized , controlled study of patients with lumbar disc herniations , operated either in a full-endoscopic or microsurgical technique . Objective . Comparison of results of lumbar discectomies in full-endoscopic interlaminar and transforaminal technique with the conventional microsurgical technique . Summary of Background Data . Even with good results , conventional disc operations may result in subsequent damage due to trauma . Endoscopic techniques have become the st and ard in many areas because of the advantages they offer intraoperatively and after surgery . With the transforaminal and interlaminar techniques , 2 full-endoscopic procedures are available for lumbar disc operations . Methods . One hundred seventy-eight patients with full-endoscopic or microsurgical discectomy underwent follow-up for 2 years . In addition to general and specific parameters , the following measuring instruments were used : VAS , German version North American Spine Society Instrument , Oswestry Low-Back Pain Disability Question naire . Results . After surgery 82 % of the patients no longer had leg pain , and 14 % had occasional pain . The clinical results were the same in both groups . The recurrence rate was 6.2 % with no difference between the groups . The full-endoscopic techniques brought significant advantages in the following areas : back pain , rehabilitation , complications , and traumatization . Conclusion . The clinical results of the full-endoscopic technique are equal to those of the microsurgical technique . At the same time , there are advantages in the operation technique and reduced traumatization . With the surgical devices and the possibility of selecting an interlaminar or posterolateral to lateral transforaminal procedure , lumbar disc herniations outside and insidethe spinal canal can be sufficiently removed using the full-endoscopic technique , when taking the appropriate criteria into account . Full-endoscopic surgery is a sufficient and safe supplementation and alternative to microsurgical procedures OBJECTIVE Minimal access surgery as a less invasive alternative to st and ard macro- and microsurgical approaches is becoming increasingly popular in the management of traumatic and degenerative spine diseases . However , data is lacking if minimal access spine surgery is indeed beneficial . This prospect i ve r and omized study was conducted to compare efficiency , safety , and outcome of st and ard open microsurgical discectomy ( SOMD ) for lumbar disc herniation with microsurgical discectomy using an 11.5 mm trocar system for minimal access to the spine . METHODS Sixty patients were r and omized to two groups of 30 patients each . Group 1 was treated by SOMD , and Group 2 was treated by minimal access microsurgical discectomy ( MAMD ) . Perioperative parameters and pre- and postoperative clinical findings including sensory or motor deficits and pain according to the visual analog scale , Oswestry Disability Index scores , and Short Form-36 results were assessed . All patients were followed for at least 6 months postoperatively ( mean , 16 mo ) . RESULTS Preoperatively , no statistically significant intergroup differences could be detected proving the comparability of both groups . Postoperatively , significant improvement of neurological symptoms and pain as measured by the visual analog scale , Oswestry Disability Index , and Short Form-36 scores could be achieved in both groups . In regard to operative time , intraoperative blood loss , and complication rate , slightly better results were observed in the MAMD group . CONCLUSIONS OMD and MAMD allow achievement of significant improvement of pain and neurological deficits in patients with lumbar disc herniations . Differences in operative time , blood loss , and complication rates were statistically not significant in MAMD compared with SOMD , indicating that , at least in lumbar disc surgery , minimal access trocar techniques are a viable alternative to st and ard spinal approaches Background : Intervertebral disc herniation is a major cause of low back pain . Several treatment methods are available for lumbar disc herniation including Chemonucleolysis , open surgery , nucleoplasty , laser disc decompression , and intradiscal electrothermal therapy . The high prevalence of lumbar disc herniation necessitates a minimally invasive yet effective treatment method . In this study , we compared the outcomes of open surgery and nucleoplasty method in patients with single lumbar disc herniation . Material s and Methods : This study was a noninferiority r and omized clinical trial conducted in one of the University Hospitals of Isfahan Medical University ; The Alzahra Hospital . About 200 patients with the diagnosis of lumbar disc herniation were recruited and were assigned to either the treatment or control groups using block r and omization . One group received open surgery and the other group received nucleoplasty as the method of treatment . Patients were revisited at 14 days , 1 , 2 , 3 months , and 1-year after surgery and were assessed for the following variables : Lower back pain , lower limb pain , common complications of surgery ( e.g. , discitis , infection and hematoma ) and recurrence of herniation . Results : The mean ( st and ard deviation ) severity of low back pain was reduced from 6.92 ( 2.5 ) to 3.43 ( 2.3 ) in the nucleoplasty group ( P = 0.04 ) and from 7.5 ( 2.2 ) to 3.04 ( 1.61 ) in the discectomy group ( P = 0.73 ) . Between group difference was not statistically significant ( P = 0.44 ) , however , time and treatment interaction was significant ( P = 0.001 ) . The level of radicular pain evaluated 1 year after treatment was reduced from 8.1 ( 1.2 ) to 2.9 ( 1.2 ) ( P = 0.004 ) and from 7.89 ( 2.1 ) to 3.6 ( 2.5 ) ( P = 0.04 ) in the discectomy and the nucleoplasty groups respectively , significant interaction between time and treatment options was observed ( P < 0.001 ) while there was no significant difference between two treatment groups ( P = 0.82 ) . Conclusion : Our results show that while nucleoplasty is as effective as open discectomy in the treatment of lumbar disc herniation , it is also less invasive with higher patient compliance . Taking factor such as decreased cost and duration of the surgery , as well as faster recovery in patients into account ; we suggest considering nucleoplasty as an effective method of treatment in patients with single-level disc herniation Factors as age , sex , smoking , duration of leg pain , working status , type/level of disc herniation and psychosocial factors have been demonstrated to be of importance for short-term results after lumbar discectomy . There are few studies with long-term follow-up . In this prospect i ve study of lumbar disc herniation patients undergoing surgery , the result was evaluated at 2 and 5–10 ( mean 7.3 ) years after surgery . Predictive factors for satisfaction with treatment and objective outcome were investigated . Out of the included 171 patients undergoing lumbar discectomy , 154 ( 90 % ) patients completed the 2-year follow-up and 140 ( 81 % ) completed the long-term follow-up . Baseline data and question naires about leg- and back pain intensity ( VAS ) , duration of leg pain , disability ( Oswestry Disability Index ) , depression ( Zung Depression Scale ) , sick leave and employment status were obtained preoperatively , at 2-year- and long-term follow-up . Primary outcome included patient satisfaction with treatment ( at both time points ) and assessment of an independent observer at the 2-year follow-up . Secondary outcomes at 2-year follow-up were improvement of leg and back pain , working capacity and the need for analgesics or sleeping pills . In about 70 % of the patients excellent or good overall result was reported at both follow-ups , with subjective outcome measurements . The objective evaluation after 2 years was in agreement with this result . Time on sick leave was found to be a clinical ly important predictor of the primary outcomes , with a potential of changing the probability of a satisfactory outcome ( both objective and subjective ) from around 50 % ( sick leave > 3 months ) to 80 % ( sick leave < 2 months ) . Time on sick leave was also an important predictor for several of the secondary outcomes ; e.g. working capacity and the need for analgesics OBJECTIVE We compared the intra- and postoperative differences , as well as the final outcome of patients with herniated lumbar discs who underwent either open discectomy ( OD ) or microendoscopic discectomy ( MED ) . METHODS We performed a prospect i ve controlled r and omized study of 40 patients with sciatica caused by lumbar disc herniations nonresponsive to conservative treatment who underwent OD or MED with a 24-month follow-up period . Pre- and postoperative neurological status , pain , and functional outcome were evaluated . Other studied variables were the duration of the procedure , blood loss , time of hospital stay , and time to return to work . Statistical analysis with a P value less than 0.005 was carried out . RESULTS The only statistically significant differences found were for size of the incision , length of hospital stay , and operative time . The former two were greater in the OD group ( P < 0.01 and P = 0.05 , respectively ) , and the latter was greater in the MED group ( P < 0.01 ) . CONCLUSION The few parameters that were found to be statistically significant between the groups did not affect the overall outcome . In the current series , the final clinical and neurological results were similarly satisfactory in both the OD and the MED groups The magnitude of the tissue damage from surgery impacts the trauma response . This response is proportional to the severity of surgical stress . Systemic cytokines are recognized as markers of postoperative tissue trauma . Microendoscopic discectomy ( MED ) recently has become popular for treating lumbar disc herniations , and is associated with favorable clinical outcomes compared with open discectomy ( OD ) . This study postulates that MED is a less traumatic procedure , and therefore has a lower surgical stress response compared to OD . In this study , a quantitative comparison of the overall effects of surgical trauma result ing from MED and OD was performed through analyzing patient systemic cytokines response . From April , 2002 to June , 2003 , 22 consecutive patients who had symptomatic lumbar disc herniations were prospect ively r and omized to undergo either intracanalicular MED ( N=10 ) or OD ( N=12 ) . In this study , the Vertebroscope System ( Zeppelin , Pullach , Germany ) was used to perform the endoscopic discectomy procedure in all MED patients . Serum levels of tumor necrosis factor-alpha ( TNF-alpha ) , Interleukin-1beta ( IL-1beta ) , Interleukin-6 ( IL-6 ) , and Interleukin-8 ( IL-8 ) were measured before surgery and at 1 , 2 , 4 , 8 and 24h after surgery using an enzyme-linked immunosorbent assay . Serum C-reactive protein ( CRP ) was measured at the same time interval . The results showed the MED patients had shorter postoperative hospital stay ( mean , 3.57+/-0.98 vs. 5.92+/-2.39 days , p=0.025 ) and less intraoperative blood loss ( mean , 87.5+/-69.4 vs. 190+/-115 ml , p=0.042 ) . The operating length , including the set-up time , was longer in the MED group ( mean , 109+/-35.9 vs. 72.1+/-17.8 min , p=0.01 ) . The mean size of skin incision made for the MED patients was 1.86+/-0.13 cm ( range 1.7 - 2.0 cm ) ; and 6.3+/-0.98 cm for the OD patients ( range 5.5 - 8 cm ) , p=0.001 . The patients ' pain severity of the involved limbs on 10-point Visual Analog Scale before operation in MED group was 7.5+/-0.3 ( range 6 - 9 ) and 8+/-0.2 ( range 7 - 9 ) in OD group , p=0.17 ; and after surgery , 1.5+/-0.2 ( range 1 - 2 ) in MED group and 1.4+/-0.1 ( range 1 - 3 ) in OD group , p=0.91 . CRP levels peaked at 24h in both groups , and OD patients displayed a significantly greater postoperative rise in serum CRP ( mean , 27.78+/-15.02 vs. 13.84+/-6.25mg/l , p=0.026 ) . Concentrations of TNF-alpha , IL-1beta , and IL-8 were detected only sporadically . Serum IL-6 increased less significantly following MED than after OD . In the MED group , IL-6 level peaked 8h after surgery , with the response statistically less than in the open group ( mean , 6.27+/-5.96 vs. 17.18+/-11.60 pg/ml , p=0.025 ) . A statistically significant correlation was identified between IL-6 and CRP values ( r=0.79 ) . Using the modified MacNab criteria , the clinical outcomes were 90 % satisfactory ( 9/10 ) in MED patients and 91.6 % satisfactory ( 11/12 ) in OD patients at a mean 18.9 months ( range 10 - 25 ) follow-up . Based on the current data , surgical trauma , as reflected by systemic IL-6 and CRP response , was significantly less following MED than following OD . The difference in the systemic cytokine response may support that the MED procedure is less traumatic . Moreover , our MED patients had achieved satisfactory clinical outcomes as the OD patients at a mean 18.9 months follow-up after surgery Purpose . To compare the outcomes of microendoscopic discectomy ( MED ) versus open discectomy for lumbar disc herniation . Methods . 80 men and 32 women aged 26 to 57 ( mean , 37 ) years with a single-level disc herniation were r and omised to undergo MED ( n=55 ) or open ( fenestration/laminotomy ) discectomy ( n=57 ) . Patients were assessed pre- and post-operatively ( at week 6 , month 6 , and year one ) . The 2 groups were compared with respect to surgical time , anaesthesia time , duration of hospital stay , intra-operative blood loss , weight of disc material removed , and self-evaluated low back pain and functional outcome ( using the Oswestry low back pain disability question naire ) . Results . Surgical and anaesthesia times were significantly longer , but blood loss and hospital stay were significantly reduced in patients having MED than open discectomy . The improvement in the Oswestry score in both groups was significant at week one , but not at other follow-ups . The complication rate was similar in both groups . One patient with MED had a recurrence of disc herniation after 7 months and was treated with open discectomy . Conclusions . Both methods are equally effective in relieving radicular pain . MED entailed shorter hospital stay , less morbidity , and earlier return to work . Nonetheless , it is a dem and ing technique and should not be attempted without specific instruction and training This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence Existing studies on micro-endoscopic lumbar discectomy report similar outcomes to those of open and microdiscectomy and conflicting results on complications . We design ed a r and omised controlled trial to investigate the hypothesis of different outcomes and complications obtainable with the three techniques . 240 patients aged 18–65 years affected by posterior lumbar disc herniation and symptoms lasting over 6 weeks of conservative management were r and omised to micro-endoscopic ( group 1 ) , micro ( group 2 ) or open ( group 3 ) discectomy . Exclusion criteria were less than 6 weeks of pain duration , cauda equina compromise , foraminal or extra-foraminal herniations , spinal stenosis , malignancy , previous spinal surgery , spinal deformity , concurrent infection and rheumatic disease . Surgery and follow-up were made at a single Institution . A biomedical research er independently collected and review ed the data . ODI , back and leg VAS and SF-36 were the outcome measures used preoperatively , postoperatively and at 6- , 12- and 24-month follow-up . 212/240 ( 91 % ) patients completed the 24-month follow-up period . VAS back and leg , ODI and SF36 scores showed clinical ly and statistically significant improvements within groups without significant difference among groups throughout follow-up . Dural tears , root injuries and recurrent herniations were significantly more common in group 1 . Wound infections were similar in group 2 and 3 , but did not affect patients in group 1 . Overall costs were significantly higher in group 1 and lower in group 3 . In conclusion , outcome measures are equivalent 2 years following lumbar discectomy with micro-endoscopy , microscopy or open technique , but severe complications are more likely and costs higher with micro-endoscopy Since its introduction in the 1970s percutaneous treatment of lumbar disc herniation has been an attractive concept that has been the object of technical development and clinical application throughout the world . Little scientific evaluation of the efficacy and effectiveness of the procedure has been done . To estimate the success rates of automated percutaneous and conventional discectomy in comparable patients and to document the re source consumption of patients treated in these ways , a multicenter r and omized clinical trial design ed to compare both treatment efficacy and cost-effectiveness of automated percutaneous discectomy and conventional discectomy in adult patients with no prior lumbar spinal surgery , no coexistent lumbar spinal disease , unilateral single level lumbar radiculopathy with images confirming disc herniation at the appropriate level . In the course of the trial important technical advances allowing epidural extraction of free-fragment disc herniation was incorporated into the trial . It was not possible to enroll the required number of patients to complete the trial . Of 5735 screened patients , 95 were eligible and 36 were enrolled . Two elected watchful waiting and did not have any surgical procedure . Eight patients were lost to follow-up . Among the 27 evaluable patients , 41 % of the percutaneous discectomy patients and 40 % of the conventional discectomy patients were assessed as achieving " success " on the primary outcome measure . No clinical trial of any percutaneous discectomy technique provides definitive evidence supporting the efficacy or effectiveness of the procedure . Such evidence should be required by patients to whom such procedures are proposed and those who are asked to pay for them Percutaneous endoscopic discectomy is a new technique for removing " contained " lumbar disc herniations ( those in which the outer border of the anulus fibrosus is intact ) and small " noncontained " lumbar disc herniations ( those at the level of the disc space and occupying less than one-third of the sagittal diameter of the spinal canal ) through a posterolateral approach with the aid of specially developed instruments . The technique combines rigid straight , angled , and flexible forceps with automated high-power suction shaver and cutter systems . Access can thus be gained to the dorsal parts of the intervertebral space where the disc herniation is located . Percutaneous endoscopic discectomy is monitored using an endoscope angled to 70 degrees coupled with a television and video unit and is performed with the patient under local anesthesia and an anesthesiologist available if needed . Its indication is restricted to discogenic root compression with a minor neurological deficit . Two groups of patients with contained or small noncontained disc herniations were treated by either percutaneous endoscopic discectomy ( 20 cases ) or microdiscectomy ( 20 cases ) . Both groups were investigated in a prospect i ve r and omized study in order to compare the efficacy of the two methods . The disc herniations were located at L2 - 3 ( one patient ) , L3 - 4 ( two patients ) , or L4 - 5 ( 37 patients ) . There were no significant differences between the two groups concerning age and sex distribution , preoperative evolution of complaints , prior conservative therapy , patient 's occupation , preoperative disability , and clinical symptomatology . Two years after percutaneous endoscopic discectomy , sciatica had disappeared in 80 % ( 16 of 20 patients ) , low-back pain in 47 % ( nine of 19 patients ) , sensory deficits in 92.3 % ( 12 of 13 patients ) , and motor deficits in the one patient affected . Two years after microdiscectomy , sciatica had disappeared in 65 % ( 13 of 20 patients ) , low-back pain in 25 % ( five of 20 patients ) , sensory deficits in 68.8 % ( 11 of 16 patients ) , and motor deficits in all patients so affected . Only 72.2 % of the patients in the microdiscectomy group had returned to their previous occupation versus 95 % in the percutaneous endoscopic discectomy group . Percutaneous endoscopic discectomy appears to offer an alternative to microdiscectomy for patients with " contained " and small subligamentous lumbar disc herniations OBJECTIVE : Minimally invasive spinal techniques have been developed for years in an attempt to minimize trauma . However , most endoscopic techniques have been unable to address uncontained or large contained disc herniations . The aim of this prospect i ve study was to compare the results of microendoscopic discectomy ( MED ) and microsurgical discectomy in the treatment of patients with uncontained or large contained disc herniations . METHODS : An independent observer review ed the treatment of 28 patients . The study group included 14 consecutive patients who underwent MED and 14 consecutive patients who underwent microsurgical discectomy for radicular pain secondary to uncontained or large contained disc herniations during the same period . Patients were followed up for an average of 12 months . They were assessed by use of Oswestry disability question naire and low back pain outcome score . RESULTS : The average outcome score improvement was of clinical significance in both patient groups . No difference in the scores was found between the two groups . Patients in the MED group required less postoperative analgesia during their stay . One patient in the MED group had a dural tear . CONCLUSION : MED is at least as effective as microsurgical discectomy for treatment of uncontained or large contained disc herniations , although the advantages over the open technique are short lived and did not reach significance . Nonetheless , for the surgeon accustomed to endoscopic techniques , MED seems to be a safe procedure A Prospect i ve r and omised controlled study was done to determine statistical difference between the st and ard microsurgical discotomy ( MC ) and a minimally invasive microscopic procedure for disc prolapse surgery by comparing operation duration and clinical outcome . Additionally , the transferability of the results was determined by a bicentric design . The microscopic assisted percutaneous nucleotomy ( MAPN ) has been advocated as a minimally invasive tubular technique . Proponents have cl aim ed that minimally invasive procedures reduce postoperative pain and accelerate the recovery . In addition , there exist only a limited number of well- design ed comparison studies comparing st and ard microdiscotomy to a tubular minimally invasive technique that support this cl aim . Furthermore , there are no well- design ed studies looking at the transferability of those results and possible learning curve phenomena . We studied 100 patients , who were planned for disc prolapse surgery at two centres [ 50 patients at the developing centre ( index ) and 50 patients at the less experienced ( transfer ) centre ] . The r and omisation was done separately for each centre , employing a block-r and omisation procedure with respect to age and preoperative Oswestry score . Operation duration was chosen as a primary outcome parameter as there was a distinguished shortening observed in a preliminary study at the index centre enabling a sound case number estimation . The following data were compared between the two groups and the centres with a 12-month follow-up : surgical times ( operation duration and approach duration ) , the clinical results , leg and back pain by visual analogue scale , the Oswestry disability index , length of hospital stay , return to work time , and complications . The operation duration was statistically identical for MC ( 57.8 ± 20.2 min ) at the index centre and for MAPN ( 50.3 ± 18.3 min ) and MC ( 54.7 ± 18.1 min ) at the transfer centre . The operation duration was only significantly shorter for the MAPN technique at the index centre with 33.3 min ( SD 12.1 min ) . There was a huge clinical improvement for all patients regardless of centre or method revealed by a repeated measures ANOVA for all follow-up visits Separate post hoc ANOVAs for each centre revealed that there was a significant time– method ( MAPN vs. MC ) interaction at the index centre ( F = 3.75 , P = 0.006 ) , whereas this crucial interaction was not present at the transfer centre ( F = 0.5 , P = 0.7 ) . These results suggest a slightly faster clinical recovery for the MAPN patients only at the index centre . This was due to a greater reduction in VAS score for back pain at discharge , 8-week and 6-month follow up ( P < 0.002 ) . The Oswestry-disability scores reached a significant improvement compared to the initial values extending over the complete follow-up at both centres for both methods without revealing any differences for the two methods in either centre . There was no difference regarding complications . The results demonstrate that a shorter operation duration and concomitant quicker recovery is comprehensible at an experienced minimally invasively operating centre . These advantages could not be found at the transfer centre within 25 minimally invasive procedures . In conclusion both procedures show equal mid term clinical results and the same complication rate even if the suggested advantages for the minimally invasive procedure could not be confirmed for the transfer centre within the framework of this study OBJECT Microdiscectomy currently constitutes the st and ard treatment for herniated lumbar discs . Although limiting surgery to excision of fragments has occasionally been suggested , prospect i ve data are lacking . Therefore , the objective of this study was to compare early outcome and recurrence rates after sequestrectomy and microdiscectomy . METHODS Eighty-four consecutive patients 60 years of age or younger who harbored free , subligamentary , or transanular herniated lumbar discs refractory to conservative treatment were r and omized to one of two treatment groups . Intraoperative parameters and findings were documented as well as pre- and postoperative symptoms such as pain , Patient Satisfaction Index ( PSI ) , Prolo Scale score , and Short Form (SF)-36 subscale results . Follow up of at least 12 months was available in 73 patients ( 87 % ) . Preoperative intergroup symptoms did not differ significantly . Surgery was significantly shorter in the sequestrectomy-treated group . Overall , low-back pain and sciatica were drastically reduced in both groups and most sensorimotor deficits improved . At 4 to 6 months , SF-36 subscales and PSI scores showed a trend in favor of sequestrectomy , leaving 3 % of patients unsatisfied compared with 18 % of those treated with discectomy . Outcome according to the Prolo Scale was good or excellent in 76 % of discectomy-treated patients and 92 % of sequestrectomy-treated patients . Reherniation occurred in four patients after discectomy ( 10 % ) and two patients after sequestrectomy ( 5 % ) within 18 months . CONCLUSIONS Sequestrectomy does not seem to entail a higher rate of early recurrences compared with microdiscectomy . Analysis of early outcome demonstrated a trend toward superior results when sequestrectomy is performed . Although long-term follow-up data are m and atory , sequestrectomy may be an advantageous alternative to st and ard microdiscectomy BACKGROUND A few recent studies dampen the euphoric reports of the value of percutaneous endoscopic lumbar discectomy ( PELD ) in the treatment of discogenic disease . We felt that a large-scale comparison between PELD and the still minimally invasive open lumbar disk surgery ( OLDS ) was called for . METHODS This report is based on the surgical experience of one year ( 1991 ) and is confined to the intervertebral disk level L4 - 5 . Three hundred thirteen patients treated by open disk surgery were compared with 13 who were selected for percutaneous discectomy . RESULTS Using careful selection criteria , only 13 ( 4 % ) of a possible 326 were considered potentially suitable for PELD . Of these , only eight were wholly suitable and were operated on percutaneously . Within the first postoperative month , 62.5 % ( 5 patients ) of the PELD group required open surgery for definitive treatment , whereas only 14 ( 4 % ) of the 313 OLDS patients had to undergo additional surgery . CONCLUSIONS Although it may of benefit to a very few , we feel that the PELD method can not be considered a substitute for , or even an alternative to , traditional surgery in most cases Microendoscopic discectomy ( MED ) , which combines traditional lumbar microsurgical techniques with endoscopy , is being used as a minimally invasive procedure for lumbar disc herniation . We review ed 30 patients who underwent MED at our institution and compared their outcome with that of patients subjected to the conventional method . Laboratory data suggested that MED was less invasive surgery . Moreover , MED allowed an early return to work . However , the difficulties of this endoscopic procedure were evident , because of the limited exposure and two-dimensional video display . The potential injury of the nerve root and prolonged surgical time remain as matters of serious concern . To overcome this problem , we used an operative magnifying glass during surgery and this helped us to accomplish the procedure comfortably . We recommend the use of an operative magnifying glass in the early stage of the introduction of MED , for it is quite useful to identify the three-dimensional relationships of the structures BACKGROUND The usefulness of video-assisted arthroscopic microdiscectomy for the treatment of a herniated lumbar disc has been studied previously . In the current prospect i ve , r and omized study , the results of this procedure were compared with those of conventional open laminotomy and discectomy . METHODS Sixty patients who had objective evidence of a single intracanalicular herniation of a lumbar disc caudad to the first lumbar vertebra were r and omized into two groups consisting of thirty patients each ; Group 1 was managed with open laminotomy and discectomy , and Group 2 was managed with video-assisted arthroscopic microdiscectomy . None of the patients had had a previous operation on the low back , and all had failed to respond to nonoperative measures . Analysis of the outcomes of both procedures was based on the patient 's self-evaluation before and after the operation , the preoperative and postoperative clinical findings , and the patient 's ability to return to a functional status . The patients were followed for nineteen to forty-two months postoperatively . RESULTS On the basis of the patient 's preoperative and postoperative self-evaluation , the findings on physical examination , and the patient 's ability to return to work or to normal activity , twenty-eight patients ( 93 percent ) in Group 1 and twenty-nine patients ( 97 percent ) in Group 2 were considered to have had a satisfactory outcome . The mean duration of postoperative disability before the patients were able to return to work was considerably longer in Group 1 than in Group 2 ( forty-nine compared with twenty-seven days ) . The patients in Group 1 used narcotics for a longer duration postoperatively . No neurovascular complications or infections were encountered in either group . CONCLUSIONS Although the rate of satisfactory outcomes was approximately the same in both groups , the patients who had had an arthroscopic microdiscectomy had a shorter duration of postoperative disability and used narcotics for a shorter period . These findings suggest that arthroscopic microdiscectomy may be useful for the operative treatment of specific symptoms , including radiculopathy , that are caused by lumbar disc herniation , provided that patients are properly selected -- that is , they must have a herniated disc at a single level as confirmed on imaging studies , have failed to respond to nonoperative management , have no evidence of spinal stenosis , and have a herniation not exceeding one-half of the anteroposterior diameter of the spinal canal . Moreover , the surgeon must be familiar with this technique and must have received training in its use Background Percutaneous laser disc decompression is a minimally invasive treatment , for lumbar disc herniation and might serve as an alternative to surgical management of sciatica . In a r and omised trial with two-year follow-up we assessed the clinical effectiveness of percutaneous laser disc decompression compared to conventional surgery . Material s and methods This multicentre r and omised prospect i ve trial with a non-inferiority design , was carried out according to an intent-to-treat protocol with full institutional review board approval . One hundred and fifteen eligible surgical c and i date s , with sciatica from a disc herniation smaller than one-third of the spinal canal , were r and omly allocated to percutaneous laser disc decompression ( n = 55 ) or conventional surgery ( n = 57 ) . The main outcome measures for this trial were the Rol and -Morris Disability Question naire for sciatica , visual analogue scores for back and leg pain and the patient 's report of perceived recovery . Results The primary outcome measures showed no significant difference or clinical ly relevant difference between the two groups at two-year follow-up . The re-operation rate was 21 % in the surgery group , which is relatively high , and with an even higher 52 % in the percutaneous laser disc decompression group . Conclusion At two-year follow-up , a strategy of percutaneous laser disc decompression , followed by surgery if needed , result ed in non-inferior outcomes compared to a strategy of microdiscectomy . Although the rate of reoperation in the percutaneous laser disc decompression group was higher than expected , surgery could be avoided in 48 % of those patients that were originally c and i date s for surgery . Percutaneous laser disc decompression , as a non-surgical method , could have a place in the treatment arsenal of sciatica caused by contained herniated discs |
783 | 25,404,855 | CONCLUSION Preliminary evidence suggests that Tai Chi has beneficial effects on exercise capacity and HRQoL in COPD patients .
This exercise can be recommended as an effective alternative training modality in pulmonary rehabilitation programs . | BACKGROUND Tai Chi is a traditional Chinese mind-body exercise that has been widely practice d in the People 's Republic of China for many centuries .
This exercise has also been applied as a training modality in pulmonary rehabilitation programs for stable chronic obstructive pulmonary disease ( COPD ) .
This systematic review and meta- analysis aim ed to assess the effects of Tai Chi on exercise capacity and health-related quality of life ( HRQoL ) in COPD patients . | BACKGROUND Preliminary evidence suggests that meditative exercise may have benefits for patients with chronic systolic heart failure ( HF ) ; this has not been rigorously tested in a large clinical sample . We sought to investigate whether tai chi , as an adjunct to st and ard care , improves functional capacity and quality of life in patients with HF . METHODS A single-blind , multisite , parallel-group , r and omized controlled trial evaluated 100 out patients with systolic HF ( New York Heart Association class I-III , left ventricular ejection fraction ≤40 % ) who were recruited between May 1 , 2005 , and September 30 , 2008 . A group-based 12-week tai chi exercise program ( n = 50 ) or time-matched education ( n = 50 , control group ) was conducted . Outcome measures included exercise capacity ( 6- minute walk test and peak oxygen uptake ) and disease-specific quality of life ( Minnesota Living With Heart Failure Question naire ) . RESULTS Mean ( SD ) age of patients was 67 ( 11 ) years ; baseline values were left ventricular ejection fraction , 29 % ( 8 % ) and peak oxygen uptake , 13.5 mL/kg/min ; the median New York Heart Association class of HF was class II . At completion of the study , there were no significant differences in change in 6-minute walk distance and peak oxygen uptake ( median change [ first quartile , third quartile ] , 35 [ -2 , 51 ] vs 2 [ -7 , 54 ] meters , P = .95 ; and 1.1 [ -1.1 , 1.5 ] vs -0.5 [ -1.2 , 1.8 ] mL/kg/min , P = .81 ) when comparing tai chi and control groups ; however , patients in the tai chi group had greater improvements in quality of life ( Minnesota Living With Heart Failure Question naire , -19 [ -23 , -3 ] vs 1 [ -16 , 3 ] , P = .02 ) . Improvements with tai chi were also seen in exercise self-efficacy ( Cardiac Exercise Self-efficacy Instrument , 0.1 [ 0.1 , 0.6 ] vs -0.3 [ -0.5 , 0.2 ] , P < .001 ) and mood ( Profile of Mood States total mood disturbance , -6 [ -17 , 1 ] vs -1 [ -13 , 10 ] , P = .01 ) . CONCLUSION Tai chi exercise may improve quality of life , mood , and exercise self-efficacy in patients with HF . Trial Registration clinical trials.gov Identifier : NCT00110227 Objectives : To study the effect of unsupported upper limb and lower limb exercise training and their combined influence on the exercise performance and health-related quality of life in COPD patients . Material s and Methods : Thirty patients were r and omly assigned to one of the three groups , through block r and omization . Of the three groups , group A received upper limb training , group B received lower limb training , and group C received both upper and lower limb training . Patients in group A , B , and C underwent exercise training five times a week for four weeks . The outcome measures used in the study were unsupported upper limb endurance test ( UULEX ) , Six-Minute Walk Test ( 6-MWT ) , and a Chronic Respiratory Question naire . Statistical analysis was performed with analysis of variance , Wilcoxon scale , and a Kruskal Wallis one way ANOVA test , and a P value of .05 was used in the study . Conclusion : The combined upper limb and lower limb training group showed a significant improvement in the exercise performance and health-related quality of life BACKGROUND Although the benefits of exercise on the health of patients with chronic obstructive pulmonary disease ( COPD ) have been widely reported , the effect of Tai Chi as an alternative exercise has not been thoroughly evaluated in patients with COPD . This study reported a r and omised controlled trial , which investigated the effects of Tai Chi on lung function , exercise capacity , and diaphragm strength in patients with COPD . TRIAL DESIGN Single blind r and omised controlled study . SETTING Department of Respiratory Medicine , Xiangya Hospital , Central South University . METHODS Forty patients with COPD were r and omised into either a control group or Tai Chi intervention group . Participants in the control group received only routine care , while participants in the Tai Chi group received routine care and completed a six-month Tai Chi exercise program . OUTCOMES Lung function parameters , blood gas parameters , 6-min walking distance ( 6MWD ) , and diaphragm strength parameters . RESULTS Lung function parameters ( FEV1 : 1.43 ± 0.08 and FEV1 ( % ) predicted : 47.6 ± 4.76 ) , 6MWD ( 476 ± 15 ) and diaphragm strength parameters ( TwPes : 1.17 ± 0.07 , TwPga : -1.12 ± 0.06 , and TwPdi : 1.81 ± 0.09 ) were found to be significantly increased in participants who successfully completed the six-month Tai Chi program compared to participants in the control group who only received routine care ( p<0.05 ) . These parameters were also found to be significantly increased in participants who completed the Tai Chi exercise program compared to the baseline ( p<0.05 ) . In contrast , no significant differences in PaO2 and PaCO2 were observed in participants before or after completing a Tai Chi program or between Tai Chi group and control group ( p>0.05 ) . CONCLUSIONS Tai Chi enhances lung function , exercise capacity , and diaphragm strength . However , this is only preliminary research data and a larger trial is needed for more detailed results OBJECTIVE To determine the feasibility of a r and omized controlled trial of the effect of a tai chi program on quality of life and exercise capacity in patients with COPD . METHODS We r and omized 10 patients with moderate to severe COPD to 12 weeks of tai chi plus usual care ( n = 5 ) or usual care alone ( n = 5 ) . The tai chi training consisted of a 1-hour class , twice weekly , that emphasized gentle movement , relaxation , meditation , and breathing techniques . Exploratory outcomes included disease-specific symptoms and quality -of-life , exercise capacity , pulmonary function tests , mood , and self-efficacy . We also conducted qualitative interviews to capture patient narratives regarding their experience with tai chi . RESULTS The patients were willing to be r and omized . Among 4 of the 5 patients in the intervention group , adherence to the study protocol was excellent . The cohort 's baseline mean ± SD age , percent-of-predicted FEV₁ , and ratio of FEV₁ to forced vital capacity were 66 ± 6 y , 50 ± 12 % , and 0.63 ± 0.14 , respectively . At 12 weeks there was significant improvement in Chronic Respiratory Question naire score among the tai chi participants ( 1.4 ± 1.1 ) , compared to the usual-care group ( -0.1 ± 0.4 ) ( P = .03 ) . There were nonsignificant trends toward improvement in 6-min walk distance ( 55 ± 47 vs -13 ± 64 m , P = .09 ) , Center for Epidemiologic Studies Depression Scale ( -9.0 ± 9.1 vs -2.8 ± 4.3 , P = .20 ) , and University of California , San Diego Shortness of Breath score ( -7.8 ± 3.5 vs -1.2 ± 11 , P = .40 ) . There were no significant changes in either group 's peak oxygen uptake . CONCLUSIONS A r and omized controlled trial of tai chi is feasible in patients with moderate to severe COPD . Tai chi exercise as an adjunct to st and ard care warrants further investigation BACKGROUND Patients with Parkinson 's disease have substantially impaired balance , leading to diminished functional ability and an increased risk of falling . Although exercise is routinely encouraged by health care providers , few programs have been proven effective . METHODS We conducted a r and omized , controlled trial to determine whether a tailored tai chi program could improve postural control in patients with idiopathic Parkinson 's disease . We r and omly assigned 195 patients with stage 1 to 4 disease on the Hoehn and Yahr staging scale ( which ranges from 1 to 5 , with higher stages indicating more severe disease ) to one of three groups : tai chi , resistance training , or stretching . The patients participated in 60-minute exercise sessions twice weekly for 24 weeks . The primary outcomes were changes from baseline in the limits-of-stability test ( maximum excursion and directional control ; range , 0 to 100 % ) . Secondary outcomes included measures of gait and strength , scores on functional-reach and timed up- and -go tests , motor scores on the Unified Parkinson 's Disease Rating Scale , and number of falls . RESULTS The tai chi group performed consistently better than the resistance-training and stretching groups in maximum excursion ( between-group difference in the change from baseline , 5.55 percentage points ; 95 % confidence interval [ CI ] , 1.12 to 9.97 ; and 11.98 percentage points ; 95 % CI , 7.21 to 16.74 , respectively ) and in directional control ( 10.45 percentage points ; 95 % CI , 3.89 to 17.00 ; and 11.38 percentage points ; 95 % CI , 5.50 to 17.27 , respectively ) . The tai chi group also performed better than the stretching group in all secondary outcomes and outperformed the resistance-training group in stride length and functional reach . Tai chi lowered the incidence of falls as compared with stretching but not as compared with resistance training . The effects of tai chi training were maintained at 3 months after the intervention . No serious adverse events were observed . CONCLUSIONS Tai chi training appears to reduce balance impairments in patients with mild-to-moderate Parkinson 's disease , with additional benefits of improved functional capacity and reduced falls . ( Funded by the National Institute of Neurological Disorders and Stroke ; Clinical Trials.gov number , NCT00611481 . ) The aims of the study were to determine the effect of short-form Sun-style t’ai chi ( SSTC ) ( part A ) and investigate exercise intensity of SSTC ( part B ) in people with chronic obstructive pulmonary disease ( COPD ) . Part A : after confirmation of eligibility , participants were r and omly allocated to either the t’ai chi group or control group ( usual medical care ) . Participants in the t’ai chi group trained twice weekly for 12 weeks . Part B : participants who had completed training in the t’ai chi group performed a peak exercise test ( incremental shuttle walk test ) and SSTC while oxygen consumption ( VO2 ) was measured . Exercise intensity of SSTC was determined by the per cent of VO2 reserve . Of 42 participants ( mean±sd forced expiratory volume in 1 s 59±16 % predicted ) , 38 completed part A and 15 completed part B. Compared to control , SSTC significantly increased endurance shuttle walk time ( mean difference 384 s , 95 % CI 186–510 ) ; reduced medial-lateral body sway in semi-t and em st and ( mean difference -12.4 mm , 95 % CI -21– -3 ) ; and increased total score on the chronic respiratory disease question naire ( mean difference 11 points , 95 % CI 4–18 ) . The exercise intensity of SSTC was 53±18 % of VO2 reserve . SSTC was an effective training modality in people with COPD achieving a moderate exercise intensity which meets the training recommendations Our aim was to determine the minimal important difference ( MID ) for 6-min walk distance ( 6MWD ) and maximal cycle exercise capacity ( MCEC ) in patients with severe chronic obstructive pulmonary disease ( COPD ) . 1,218 patients enrolled in the National Emphysema Treatment Trial completed exercise tests before and after 4–6 weeks of pre-trial rehabilitation , and 6 months after r and omisation to surgery or medical care . The St George 's Respiratory Question naire ( domain and total scores ) and University of California San Diego Shortness of Breath Question naire ( total score ) served as anchors for anchor-based MID estimates . In order to calculate distribution-based estimates , we used the st and ard error of measurement , Cohen 's effect size and the empirical rule effect size . Anchor-based estimates for the 6MWD were 18.9 m ( 95 % CI 18.1–20.1 m ) , 24.2 m ( 95 % CI 23.4–25.4 m ) , 24.6 m ( 95 % CI 23.4–25.7 m ) and 26.4 m ( 95 % CI 25.4–27.4 m ) , which were similar to distribution-based MID estimates of 25.7 , 26.8 and 30.6 m. For MCEC , anchor-based estimates for the MID were 2.2 W ( 95 % CI 2.0–2.4 W ) , 3.2 W ( 95 % CI 3.0–3.4 W ) , 3.2 W ( 95 % CI 3.0–3.4 W ) and 3.3 W ( 95 % CI 3.0–3.5 W ) , while distribution-based estimates were 5.3 and 5.5 W. We suggest a MID of 26±2 m for 6MWD and 4±1 W for MCEC for patients with severe COPD BACKGROUND Exercise tolerance is an important clinical aspect of chronic obstructive pulmonary disease that can be easily and reliably measured with the 6-minute walking test ( 6MWT ) . To improve the utility of the 6MWT for patient and health care system management , the interpretation of the functional status measure in relation to death and hospitalization should be eluci date d. METHODS Three-year , prospect i ve , multicenter observational study to evaluate the predictive power of 6MWD for death or exacerbation-related hospitalization and to evaluate the factors that help determine 6MWD . RESULTS We measured 6MWD at baseline and annually in 2110 patients with clinical ly stable Global Initiative for Obstructive Lung Disease ( GOLD ) stage II-IV COPD and recorded exacerbation-related hospitalizations and all-cause mortality . During the study , 200 patients died and 650 were hospitalized . Using receiver operating characteristics , the best predictive thresholds of the 6MWD were 334 m for increased risk of death and 357 m for exacerbation-related hospitalization ( area under the curve 0.67 and 0.60 respectively ) ; however , the discriminatory thresholds , especially for mortality , were influenced by age . The mean ( SE ) 6MWD declined by 1.6 ( 1.2 ) m per year in GOLD II , 9.8 ( 1.3 ) m per year in GOLD III , and 8.5 ( 2.4 ) m per year in GOLD IV . CONCLUSION The 6MWD provides prognostic information that may be useful for identifying high-risk patients with COPD BACKGROUND : The effects of different exercise training programs on the level of physical activity in daily life in patients with COPD remain to be investigated . OBJECTIVE : In patients with COPD we compared the effects of 2 exercise/training regimens ( a high-intensity whole-body endurance- and -strength program , and a low-intensity calisthenics- and -breathing-exercises program ) on physical activity in daily life , exercise capacity , muscle force , health-related quality of life , and functional status . METHODS : We r and omized 40 patients with COPD to perform either endurance- and -strength training ( no. = 20 , mean ± SD FEV1 40 ± 13 % of predicted ) at 60–75 % of maximum capacity , or calisthenics- and -breathing-exercises training ( no. = 20 , mean ± SD FEV1 39 ± 14 % of predicted ) . Both groups underwent 3 sessions per week for 12 weeks . Before and after the training programs the patients underwent activity monitoring with motion sensors , incremental cycle-ergometry , 6-min walk test , and peripheral-muscle-force test , and responded to question naires on health-related quality of life and functional status ( activities of daily living , pulmonary functional status , and dyspnea ) . RESULTS : Time spent active and energy expenditure in daily life were not significantly altered in either group . Exercise capacity and muscle force significantly improved only in the endurance- and -strength group . Health-related quality of life and functional status improved significantly in both groups . CONCLUSIONS : Neither training program significantly improved time spent active or energy expenditure in daily life . The training regimens similarly improved quality of life and functional status . Exercise capacity and muscle force significantly improved only in the high-intensity endurance- and -strength group BACKGROUND Exercise training programmes for patients with COPD are effective in improving exercise capacity . The few trials that have investigated the effects of exercise programmes on daily physical activity show contradictory results . AIM To investigate the relation between daily physical activity level and exercise capacity in patients with COPD using data of a r and omised controlled trial in which the exercise intervention was aim ed at improvement of both physical activity and exercise capacity ( the COPE-II study ) . METHODS These are secondary analyses of the COPE-II study , a r and omised controlled trial in which a community-based physiotherapeutic exercise programme was evaluated . Daily physical activity was measured with a pedometer ( steps/day ) . Exercise capacity was measured with an incremental maximal cycle ergometer test , the incremental ( ISWT ) and endurance shuttle walk test ( ESWT ) . Pearson correlation coefficients were calculated . RESULTS At baseline , correlations between steps/day and VO(2peak ) , ISWT ( m ) , ESWT ( m ) and ESWT ( s ) were 0.54 , 0.59 , 0.44 , and 0.34 , respectively ( all p < 0.01 ) . In the intervention group , correlations between change in steps/day over 7 months and change in ISWT ( m ) , ESWT ( m ) and ESWT ( s ) were 0.47 , 0.41 , and 0.38 , respectively ( all p < 0.01 ) . In the control group , these same correlations were weak to non-existent . CONCLUSIONS A moderate to weak relationship was found between daily physical activity and exercise capacity . These results strengthen our beliefs that exercise interventions need to target not only exercise capacity but also behaviour change with regard to daily physical activity to achieve improvements in both parameters Purpose This paper evaluates the effectiveness of a 3-month Tai chi Qigong ( TCQ ) program in promoting the psychosocial functional health of clients with chronic obstructive pulmonary disease ( COPD ) in Hong Kong . Methods This study employed a single-blind , r and omized controlled trial . Two hundred and six COPD clients were r and omly assigned into three groups , namely , TCQ group , exercise group , and control group . Subjects in the TCQ group received a TCQ program , consisting of two 60-min sessions each week for 3 months . Subjects in the exercise group were taught to practice breathing techniques combined with walking as an exercise . Subjects in the control group received their usual care . Data collection s were performed at baseline , on the sixth week and on the third month . The primary outcomes were health-related quality of life using St. George Respiratory Question naire-Hong Kong Chinese version and perceived social support using the Multidimensional Scale of Perceived Social Support-Chinese version . Results The TCQ group showed greater improvements in the symptom ( F4 , 404 = 3.351 , P = 0.010 ) and activity domains ( F4 , 404 = 2.611 , P = 0.035 ) . No differences were detected in perceived social support among the three groups . Conclusions Tai chi Qigong promoted health outcomes with respect to clients ’ perception of their respiratory symptoms . Moreover , TCQ decreased disturbances to their physical activities & NA ; The purpose of this study was to determine the levels of change on st and ard pain scales that represent clinical ly important differences to patients . Data from analgesic studies are often difficult to interpret because the clinical importance of the results is not obvious . Differences between groups , as summarized by a change in mean values over time , can be difficult to apply to clinical care . Baseline scores vary widely and group mean differences could reflect large changes in a few patients , small changes in many patients , or any combination of these outcomes . Determination of the proportion of patients who have a clinical ly important improvement in their pain would provide a more interpretable result with direct clinical implication s. However , determining a clinical ly important outcome requires information about the degree of change over time that is clinical ly important . Data from the titration phase of a multiple cross‐over r and omized clinical trial of oral transmucosal fentanyl citrate ( OTFC ) for the treatment of cancer‐related breakthrough pain were re‐analyzed to examine the differences in pain scores between treatment episodes that did and did not yield adequate pain relief . The scales evaluated were absolute pain intensity difference ( PID , 0–10 scale ) , percentage pain intensity difference ( PID% , 0–100 % scale ) , pain relief ( PR , 0 ( none ) , 1 ( slight ) , 2 ( moderate ) , 3 ( lots ) , 4 ( complete ) ) , sum of the pain intensity difference ( SPID over 60 min ) , percentage of maximum total pain relief ( % Max TOTPAR over 60 min ) , and global medication performance ( 0 ( poor ) , 1 ( fair ) , 2 ( good ) , 3 ( very good ) , 4 ( excellent ) ) . Adequate relief was defined by the patient 's decision not to use another dose of opioid medication as a rescue , in addition to the study medication , to treat each painful episode . One hundred thirty OTFC naive patients contributed data on 1268 episodes of breakthrough pain . The scales that were converted to a percentage change yielded the best accuracy in predicting adequate relief , with balanced sensitivity and specificity . The best cut‐off point for both the % Max TOTPAR and the PID% was 33 % . The best cut‐off points for the absolute scales were absolute pain intensity difference of 2 , pain relief of 2 ( moderate ) , and SPID of 2 . The global medication performance of 2 ( good ) had excellent values as well . This study presents data ‐derived cut‐off points for the changes in several pain scales , each reflecting the clinical ly important improvement for patients treating breakthrough cancer pain episodes with OTFC . Confirmation in other patient population s and different pain syndromes will be needed . The use of consistent clinical ly important cut‐off points as the primary outcome in future pain therapy clinical trials will enhance their validity , comparability , and clinical applicability OBJECTIVE To establish the minimal important difference ( MID ) for the six-minute walk distance ( 6MWD ) in persons with chronic obstructive pulmonary disease ( COPD ) . DESIGN Analysis of data from an observational study using distribution- and anchor-based methods to determine the MID in 6MWD . SETTING Outpatient pulmonary rehabilitation program at 2 teaching hospitals . PARTICIPANTS Seventy-five patients with COPD ( 44 men ) in a stable clinical state with mean age 70 years ( SD 9 y ) , forced expiratory volume in one second 52 % ( SD 21 % ) predicted and baseline walking distance 359 meters ( SD 104 m ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Participants completed the six-minute walk test before and after a 7-week pulmonary rehabilitation program . Participants and clinicians completed a global rating of change score while blinded to the change in 6MWD . RESULTS The mean change in 6MWD in participants who reported themselves to be unchanged was 17.7 meters , compared with 60.2 meters in those who reported small change and 78.4 meters in those who reported substantial change ( P=.004 ) . Anchor-based methods identified an MID of 25 meters ( 95 % confidence interval 20 - 61 m ) . There was excellent agreement with distribution-based methods ( 25.5 - 26.5 m , kappa=.95 ) . A change in 6MWD of 14 % compared with baseline also represented a clinical ly important effect ; this threshold was less sensitive than for absolute change ( sensitivity .70 vs .85 ) . CONCLUSIONS The MID for 6MWD in COPD is 25 meters . Absolute change in 6MWD is a more sensitive indicator than percentage change from baseline . These data support the use of 6MWD as a patient-important outcome in research and clinical practice OBJECTIVE To evaluate the effects of shadow boxing training on the exercise endurance and quality of life of Chinese patients with COPD ( chronic obstructive pulmonary disease ) . METHODS From May 2010 to March 2011 , a total of 70 COPD patients in stable phases were recruited from Liwan , Yuexiu and Haizhu districts of Guangzhou . There were 35 patients in the shadow boxing exercise group and 35 patients in the control group . And they were matched by gender and age . The patients in the shadow boxing group exercised for 3 months while those in the control group received the conventional out-hospital management only . Their demographic , medical history , smoking status , medicinal use , spirometric data , clinical COPD question naire ( CCQ ) scores , 6-minute walking distance and Borg scores were collected before and after trial . RESULTS A total of 63 COPD patients ( 33 in shadow boxing group vs. 30 in control group ) completed the study . There was an average dropout rate of 5.7 % ( 2/35 ) in shadow boxing group and 14.3 % ( 5/35 ) in control group . No differences existed between two groups in age ( 67 ± 8 vs 69 ± 9 yr ) , male proportion ( 84.8 % vs 86.7 % ) , body mass index ( 22.8 ± 2.6 vs 22.7 ± 3.0 ) , usage proportion of medicine ( 42.4 % vs 33.3 % ) , duration of disease ( 4.0 ± 7.5 vs 5.5 ± 7.3 ) , percentage of smokers ( 78.8 % vs 80.0 % ) , 6-minute walking distance ( 447 ± 94 vs 414 ± 100 ) , CCQ total score ( 15.0 ± 9.4 vs 14.1 ± 8.8 ) , CCQ symptom score ( 9.2 ± 5.6 vs 8.3 ± 5.0 ) and activity score ( 5.8 ± 4.5 vs 5.8 ± 4.4 ) at baseline ( all P > 0.05 ) . At the end of study , the 6-minute walking distance of patients had statistical differences between two groups ( P < 0.01 ) . The shadow boxing group increased by ( 51 ± 55 ) m while the control dropped by ( 19 ± 58 ) m. The total score , symptom score and activity score of clinical COPD question naire had statistical differences between two groups . They decreased significantly in the shadow boxing group as compared with the baseline data while there was no significant change in the control group . No statistical differences existed between two groups in the changes of forced vital capacity ( FVC ) , forced expiratory volume in one second ( FEV(1 ) ) , FEV(1)% pred , Borg score and dyspnea scales . CONCLUSION Capable of improving the exercise endurance and life quality of COPD patients , shadow boxing exercise may become one of effective rehabilitation programs for COPD patients in stable phases in communities UNLABELLED The effectiveness of exercise training in people with COPD is well established . However , alternative methods of training such as Tai Chi have not been widely evaluated . This paper describes the study design of a clinical trial which aims to determine if short form Sun-style Tai Chi improves exercise capacity and quality of life in people with COPD . METHOD This r and omised controlled trial will be conducted with concealed allocation and blinded outcome assessment . Participants will be recruited from Concord Repatriation General Hospital , Sydney . After baseline measurement , participants will be r and omised into either a Tai Chi Group or a Control Group . Participants in the Tai Chi Group will undergo supervised training twice weekly for twelve weeks . Participants in the Control Group will undergo usual medical care . Measurements will be taken at baseline ( week 0 ) and after the study period ( week 12 ) . The primary outcome measurement is endurance walking capacity assessed by the endurance shuttle walk test . Secondary outcomes include measures related to peak walking capacity , physical performance , balance , muscle strength and quality of life . Details of the physiological responses during Tai Chi will be collected in a small cohort to determine the training intensity of Sun-style Tai Chi . DISCUSSION If short form Sun-style Tai Chi improves exercise capacity , physical performance and quality of life in people with COPD , this would provide an alternate form of exercise training which does not require exercise equipment thus making effective exercise training more accessible for the large numbers of people with COPD BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . PURPOSE To create a maximum tolerated 45-minute aerobic training program for patients with chronic obstructive pulmonary disease ( COPD ) and to compare its outcomes with those of commonly prescribed moderate exercise . DESIGN Prospect i ve , r and omized trial . SETTING A work physiology laboratory . PATIENTS AND METHODS The maximum exercise intensities that 7 COPD patients could sustain for 45 minutes were determined on a bilevel exercise ergometer . The patients then exercised 45 minutes daily , 5 days a week for 6 weeks , working 2.03+/-0.4 kJ/kg per session . They were matched with 6 COPD patients who pushed an O2 cart for 45 minutes daily , 5 days a week for 6 weeks , working 1.44+/-.35 kJ/kg per session . RESULTS A 45 minute maximal regimen was established by alternating 1-minute peak exercise at peak VO2-levels with 4 minutes at the ventilatory anaerobic threshold or at 40 % of peak VO2 . Maximal bilevel training significantly decreased dyspnea at rest ( p < or = .01 ) and the blood lactate level during submaximal exercise ( p<.001 ) , and increased peak VO2 and total physical work ( p<.01 ) , maximum inspiratory and expiratory pressures ( p<.01 ) , and grip and forearm strength and endurance ( p<.01 ) . The training also increased maximum voluntary ventilation while decreasing the ventilatory equivalent during exercise ( p<.001 ) . The O2 cart pushers significantly improved only on the 12-minute walk ( p<.05 ) . CONCLUSIONS A maximally intense anaerobic exercise program can be created for most COPD patients that can significantly improve both skeletal and respiratory muscle strength and endurance as well as dyspnea and physiologic parameters AIMS AND OBJECTIVES To assess the effects of respiratory training on lung function , activity tolerance and quality of life in patients with chronic obstructive pulmonary disease . BACKGROUND For patients with chronic obstructive pulmonary disease , pulmonary rehabilitation can increase activity tolerance and improve their psychological state by relieving dyspnoea and promoting their quality of life . DESIGN A r and omised clinical trial was conducted in a local hospital . METHODS Patients with chronic obstructive pulmonary disease were r and omly assigned to intervention ( n=20 ) and control groups ( n=20 ) . Spirometry , six-minute walking distance and quality of life were used to assess the efficacy of respiratory training programme . RESULTS Significant improvement in lung function , including forced vital capacity ( p=0.037 ) , forced expiratory volume in one-second ( p=0.006 ) and per cent predicted forced expiratory volume in one-second ( p=0.008 ) in the intervention group . Regarding efficacy of the training programme for patients with chronic obstructive pulmonary disease , in forced expiratory volume in one-second ( p=0.024 ) and per cent predicted forced expiratory volume in one-second ( p=0.035 ) , six-minute walking distance significantly increased . In addition , there were significant improvements for symptoms ( p=0.018 ) , impact ( p<0.001 ) and total quality of life scores ( p<0.001 ) , as well as significantly decreased body mass , airflow obstruction , dyspnoea and exercise capacity index ( p=0.004 ) in the intervention group . CONCLUSIONS A respiratory training programme for patients with chronic obstructive pulmonary disease was found to relieve dyspnoea , maintain lung function , increase activity tolerance and improve quality of life . RELEVANCE TO CLINICAL PRACTICE Respiratory training programme can be used as a routine rehabilitation protocol for patients with chronic obstructive pulmonary disease and can be used by nurses as a reference to monitor chronic obstructive pulmonary disease patients ' health status OBJECTIVE To evaluate the effectiveness of a Tai chi Qigong ( TCQ ) program in enhancing respiratory functions and activity tolerance in clients with chronic obstructive pulmonary disease ( COPD ) . DESIGN A single-blind , r and omized controlled trial . SETTING Five general outpatient clinics in Hong Kong . INTERVENTION In total , 206 COPD clients were r and omly assigned into one of the three groups , namely , TCQ , exercise , and control group . Subjects in the TCQ group received a TCQ program consisting of two 60-min sessions each week for three months . Subjects in the exercise group were taught to practice breathing techniques combined with walking as an exercise . Subjects in the control group were instructed to maintain their usual activities . Data collection was performed at baseline and at the 6-week and 3-month marks . OUTCOMES Lung functions , 6-min walk test , and COPD exacerbation rate . RESULTS Results of repeated measures of analysis of covariance demonstrated that there were significant interaction effects between time and group in forced vital capacity ( p=.002 , η(2)=.06 ) , forced expiratory volume in 1s ( p<.001 , η(2)=.02 ) , walking distance ( p<.001 ) , and exacerbation rate ( p=.006 , η(2)=.06 ) at 3 months . Improvements were noted in the TCQ group . No changes were observed in the exercise group , while a decline in lung functions was noticed in the control group . CONCLUSION Tai chi Qigong was able to improve respiratory functions and activity tolerance level in COPD clients . The breathing and walking exercise helped maintain lung functions and slow down disease progression |
784 | 21,373,898 | The overall hemorrhage rate of 4.1 % found in this meta- analysis shows that coblation is a safe and effective technique for tonsillectomies with a secondary bleeding rate similar to what is reported for comparable techniques such as bipolar diathermia | After the surgical procedure of tonsillectomy , hemorrhage ranks among its serious postoperative complications .
In this systematic review , we analyze hemorrhage following tonsillectomies performed using the coblation technique . | OBJECTIVE Tonsillectomy has been described using a number of techniques . Recently Coblation Technology has been used to remove tonsils with anecdotal evidence of a reduction in post-operative morbidity . In this study we aim to see if there is any difference in post-operative pain , tonsillar fossae healing and return to a normal diet performing tonsillectomy , using tissue coblation compared with st and ard bipolar dissection . METHODS A double blind r and omised control trial to compare the technique of tissue coblation with st and ard bipolar dissection to remove tonsils in 38 children on the waiting list for tonsillectomy , with a history of chronic tonsillitis or obstructive tonsils . RESULTS A significant reduction in post-operative pain was found in the children whose tonsils were removed by tissue coblation ( P<0.0001 ) . More rapid healing of the tonsillar fossae was found in the coblation group . Children who had their tonsils removed by coblation were found to return to their normal diet far sooner than those who underwent bipolar dissection . There were no episodes of primary or secondary haemorrhage in either group . CONCLUSIONS This new technique using tissue coblation for tonsil removal offers significant advantages in the post-operative period , with rapid return to a normal diet and a drastic reduction in analgesic requirements following the surgery Objectives : The purpose of this study was to establish if children experienced any difference in pain , between coblation tonsillectomy and coblation tonsillotomy OBJECTIVES : The objective of this study was to compare the safety , difficulty of removal , and postoperative pain profile of radiofrequency ablation versus st and ard electrocautery removal of tonsils . STUDY DESIGN AND SETTING : A prospect i ve , blinded study was design ed to remove 1 tonsil with each of the 2 methods . Time of operation , estimated blood loss , difficulty of operation , postoperative pain , rate of postoperative hemorrhage , and the patient 's preferred technique were evaluated . RESULTS : The operating time was significantly longer ( P < 0.007 ) and the patients reported significantly less pain ( P < 0.001 ) with radiofrequency ablation . There were no differences in blood loss , difficulty of operation , or postoperative hemorrhage rates . The patients preferred the radiofrequency ablation technique ( P < 0.001 ) . CONCLUSION : Radiofrequency ablation is a viable method to remove tonsillar tissue . Operating time for this procedure will likely decrease with experience . There was significantly less pain reported with radiofrequency ablation compared with st and ard electrocautery . ( Otolaryngol Head Neck Surg 2004;130:300–5 . Tonsillectomy has been performed by a number of techniques . This double blind r and omized controlled study compares the technique of tissue coblation with bipolar dissection for the removal of tonsils in 10 adult patients with a history of chronic tonsillitis . A significant reduction in post-operative pain and more rapid healing of the tonsillar fossae were found in the side removed by tissue coblation . There were no episodes of primary or secondary haemorrhage on either side . This new technique for tonsil removal warrants further study OBJECTIVE To determine the efficacy of intracapsular tonsillectomy using low-temperature plasma excision for improving the quality of the postoperative experience and for treating obstructive symptoms through 12 months postoperatively . DESIGN Prospect i ve , r and omized , controlled , single-blind study . SETTING Multiple private or institutional otolaryngology clinics . PATIENTS Fifty-five children ( aged 3 - 12 years ) with obstructive tonsillar hypertrophy . INTERVENTION Patients were r and omly assigned and blinded to undergo either intracapsular tonsillectomy using low-temperature plasma excision ( n = 27 ) or total tonsillectomy using conventional electrosurgery ( n = 28 ) . MAIN OUTCOME MEASURES Operative data , 14-day recovery variables , and obstructive symptoms were prospect ively collected through 12 months . RESULTS During the first 14 days , significantly fewer children in the intracapsular group reported nausea ( P = .01 ) or lost weight ( P = .003 ) . The intracapsular group had a significantly faster resolution of pain ( P = .01 ) , had an earlier return to a normal diet ( P = .004 ) , ceased taking pain medication sooner ( P = .002 ) , and returned to normal activity sooner ( P = .04 ) . Postoperatively , the intracapsular group had more residual tonsil tissue than the total tonsillectomy group ( P = .002 for the 3- and 12-month visits ) . However , the incidence of recurring obstructive symptoms , pharyngitis , and antibiotic use was similar in both treatment groups during the 12 months . CONCLUSIONS Postoperative morbidity normally associated with traditional ( total ) tonsillectomy was significantly reduced after intracapsular tonsillectomy using low-temperature plasma excision . The residual tonsillar tissue associated with this technique was of no clinical consequence Coblation tonsillectomy has shown promising results with respect to postoperative pain when compared with other techniques . Our study was design ed to compare this technique with bipolar scissor tonsillectomy . Forty adult patients with a history of chronic or recurrent tonsillitis referred for st and ard tonsillectomy were recruited and r and omized into two groups . Twenty were operated with Coblator and 20 with bipolar scissors . Exclusion criteria were a history of quinsy , bleeding disorder , or any major health problems . All participants completed the study . Postoperative pain , return to normal diet , and estimated need for sick leave were utilized as parameters . Data on operative time , difficulty of tissue removal , and hemostasis were also analyzed . Operative time was longer ( P < 0.001 ) and tissue removal as well as hemostasis control were more difficult ( P = 0.005 , P = 0.013 ) with Coblator than with bipolar scissors . Participants in Coblator group assessed higher pain scores 1 and 3 h postoperatively ( P = 0.044 , P = 0.036 ) . From the time of extubation , patients had access to an opioid ( fentanyl ) via a self-controlled analgesia device . The number of doses of analgesics needed during the hospital stay was significantly higher in the Coblator group ( P = 0.020 ) . During the 14-day follow-up , no significant differences were found in pain scores , return to solid food or subjective working ability between the groups . Considering the overall outcome of the patients the results did not favor coblation technique over bipolar scissors BACKGROUND Quantum molecular resonance coagulation is an innovative technology that uses molecular resonance to cut and coagulate precisely , cleanly , and hemostatically at low tissue temperature levels . This technology offers a new possibility for tonsillectomy . OBJECTIVES To compare molecular resonance ( MRT ) with coblation ( CAT ) devices for pediatric tonsillectomy . STUDY DESIGN Prospect i ve , two-group , r and omized trial in a tertiary care pediatric institution . One hundred fifty-seven children for whom tonsillectomy was indicated were r and omly assigned to receive MRT ( n = 79 ) or CAT ( n = 78 ) . Main outcome measures included intraoperative time , blood loss , postoperative pain , and weight loss . Histopathologic examination was performed on all excised tonsils . Patients , parents , and pathologist were blinded to surgical modality . RESULTS Histopathologic evaluation revealed significantly reduced thermal injury with MRT than with CAT ( 43 microns vs. 126 , respectively , P < .001 ) , and was statistically associated with reduced muscular , blood vessel , and nerve fiber damage . No intraoperative blood loss was observed in patients following MRT . Statistically significant reduced pain scores were related to the MRT ( P < .002 ) . In addition , the MRT method showed a quick return to normal diet with even weight gain during the 10-day postoperative period . One child in the CAT group experienced delayed bleeding and required readmission . CONCLUSIONS Molecular resonance for pediatric tonsillectomy result ed in significantly reduced histopathologic thermal injury and lower pain scores compared with coblation . Further studies are advised to support these data OBJECTIVE : To compare the postoperative recovery of patients who undergo intracapsular to subcapsular Coblation tonsillectomy . STUDY DESIGN AND SETTING : This was a prospect i ve , r and omized , double-blinded study . A total of 69 children , aged 2 to 16 years , were r and omized to intracapsular ( n = 34 ) or subcapsular ( n = 35 ) tonsillectomy . The Coblation technique was used with both groups . Outcomes measures were assessed on postoperative day 1 or 2 and 5 or 6 . These included child and parental rating of pain with the Wong Faces pain scale , analgesic use , oral intake , and activity level . RESULTS : Intracapsular tonsillectomy patients had similar levels of pain to subcapsular tonsillectomy patients on day 1 or 2 . However , at day 5 or 6 , intracapsular tonsillectomy patients had significantly less pain than the subcapsular tonsillectomy patients . Intracapsular patients ate more and were more active at both time points . CONCLUSION AND SIGNIFICANCE : Children with obstructive sleep apnea who undergo tonsillectomy demonstrate better postoperative recovery after intracapsular tonsillectomy . The intracapsular versus subcapsular difference may be best appreciated at a delayed time point ( day 5 or 6 ) rather than early ( day 1 or 2 ) OBJECTIVE To compare plasma-mediated ablation ( PMA ) with monopolar electrosurgery ( MES ) for pediatric tonsillectomy . DESIGN Prospect i ve , r and omized , blinded study . SETTING Academic children 's hospital . PARTICIPANTS Thirty-four children , aged 4 to 7 years . INTERVENTIONS Tonsillectomy by means of PMA ( n = 17 ) or MES ( n = 17 ) . OUTCOME MEASURES We measured surgical efficacy , estimated blood loss , and surgical time during tonsillectomy and morphine use , immediate postoperative pain , and recovery scores after tonsillectomy . Parents recorded recovery of normal diet and activity and their own return to work for 10 days after surgery . Histopathologic evaluation of excised tonsils was performed . We review ed medical records and attempted follow-up telephone contact . RESULTS With no significant difference in blood loss compared with MES , PMA was effective for tonsillectomy . Performance of PMA took longer ( 24 vs 16 minutes ; P = .002 ) . Results of histopathologic evaluation showed less thermal injury with PMA than with MES ( P = .03 ) . Morphine consumption , pain , and recovery scores were equivalent between groups . We found no significant difference in recovery of normal diet and activity or parental return to work . Patients undergoing PMA had a greater number of perioperative complications than those undergoing MES , including 2 patients in the PMA group ( compared with none in the MES group ) who required unplanned admission for postoperative airway obstruction . CONCLUSIONS Plasma-mediated ablation for pediatric tonsillectomy result ed in less histopathologic thermal injury than MES , but did not show a statistically faster recovery to normal activity and diet or parental return to work . In addition , PMA took longer to perform , and had more complications . Therefore , PMA should not replace MES for pediatric tonsillectomy . The reduced thermal injury with PMA supports investigation into other means of using plasma ablation to treat tonsillar hypertrophy OBJECTIVES To determine if the coblation tonsillectomy ( subcapsular dissection ) results in less postoperative pain , equivalent intraoperative blood loss , equivalent postoperative hemorrhage rates , and faster healing compared with tonsillectomy was performed using unipolar electrocautery in adult patients . STUDY DESIGN The authors conducted a prospect i ve clinical trial . METHODS Forty-eight patients underwent tonsillectomy and were r and omly assigned to have one tonsil removed with coblation and the other with unipolar electrocautery . Outcome measures included time to remove each tonsil , intraoperative blood loss , patient-reported pain , postoperative hemorrhage , and amount of healing 2 weeks after surgery . RESULTS Mean time to remove a single tonsil with coblation and electrocautery was 8.22 minutes and 6.33 minutes , respectively ( P = .011 ) . Mean intraoperative blood loss for each technique was less than 10 mL. Postoperative pain was significantly less with coblation as compared with electrocautery : 18.6 % less painful during the first week of recovery . Seventy percent of blinded patients identified the coblation side as less painful during the overall 14-day convalescent period . Postoperative hemorrhage rates ( 2.1 % for coblation and 6.2 % for electrocautery ) were not significantly different . No difference in tonsillar fossa healing was observed between the two techniques 2 weeks after surgery . During nine of the 48 surgeries , wires on the tip of the coblation h and piece experienced thinning to the point of discontinuity while removing a single tonsil . CONCLUSIONS Coblation subcapsular tonsillectomy was less painful than electrocautery tonsillectomy in this 48-patient group . On average , intraoperative blood loss was less than 10 mL for both techniques . Postoperative hemorrhage rates and the degree of tonsillar fossa healing were similar between the two techniques . The coblation h and piece experienced degradation of vital wires in 18 % of cases necessitating the use of a second , new h and piece Objectives : The aim of this study was to compare postoperative symptoms following coblation tonsillectomy with those experienced following a traditional cold dissection INTRODUCTION Coblation tonsillectomy is a relatively recently introduced surgical technique which attempts to bridge the gap between ' hot ' and ' cold ' tonsillectomy methods . AIM To compare coblation tonsillectomy with three commonly used surgical techniques : cold dissection-ligation , monopolar electrocautery and CO2 laser . MATERIAL S AND METHODS A prospect i ve , r and omised , double-blinded clinical trial was undertaken of 60 adult patients divided into three equal study groups . Patients in each group were r and omly assigned to have one tonsil removed with coblation and the second with one of the other three tonsillectomy techniques . Ten r and omly selected tonsils resected by each method were sent for histopathological evaluation . RESULTS Coblation was significantly faster to perform than laser and produced significantly less intra-operative blood loss than both the dissection-ligation and laser techniques . Subjective visual analogue scale comparisons showed a non-significant pain score difference between coblation and dissection-ligation on most post-operative days . Coblation produced consistently highly significantly ( p < 0.001 ) less pain , compared with electrocautery up to the 12th post-operative day and laser up to the 10th post-operative day . There was no significant difference in tonsillar fossa healing , comparing coblation to both dissection-ligation and laser techniques . Monopolar electrocautery produced significantly slower healing than coblation after 7 post-operative days , with no significant difference after 15 post-operative days . Histopathological evaluation showed that coblation inflicted significantly less thermal tissue injury than either electrocautery ( p = 0.001 ) or laser ( p = 0.003 ) . CONCLUSIONS In adult patients , coblation tonsillectomy offers some significant advantages in terms of post-operative pain and healing , compared with other tonsillectomy techniques Objective Comparison of coblation and monopolar electrocautery tonsillectomy in terms of postoperative pain and recovery . Study Design Prospect i ve double-blind r and omized controlled trial . Methods Patients with recurrent tonsillitis requiring tonsillectomy were r and omized to 2 groups : coblation or monopolar electrocautery tonsillectomy . Postoperative pain , complications , and days taken to return to work and normal diet were compared and analyzed with the aid of a pain diary , given to the patient . Results 67 patients were recruited . Patients undergoing coblation tonsillectomy were able to return to normal diet in a shorter space of time following surgery . Patients undergoing coblation tonsillectomy were more likely to recommend the surgery than patients undergoing electrocautery tonsillectomy . No significant differences in the daily visual analog score for pain were seen for both groups of patients . Conclusions Our results showed that coblation tonsillectomy has a faster recovery period and may offer advantages when compared to monopolar electrocautery tonsillectomy OBJECTIVES : To compare postoperative tonsillectomy pain between 3 commonly used surgical devices : the Harmonic Ultrasonic Scalpel ( Ethicon Endo-Surgery , Cincinnati , OH ) , the Coblator ( ArthroCare Corp , Sunnyvale , CA ) , and electrocautery . STUDY DESIGN AND SETTING : A prospect i ve , r and omized trial . One hundred thirty-four patients were r and omly assigned to receive a tonsillectomy with 1 of 3 surgical devices . All patients were asked to fill out a postoperative diary . RESULTS : Statistically significant differences in pain scores were revealed between the Coblator and electrocautery ( P = 0.02 ) and between the Coblator and the Ultrasonic Scalpel ( P = 0.003 ) , with the Coblator having lower pain scores . Electrocautery and the Ultrasonic Scalpel did not differ significantly from each other . The Coblation method showed a strong trend toward quicker return to normal diet . CONCLUSION : Patients undergoing tonsillectomy with the Coblator device reported less pain over a 10-day period than patients undergoing tonsillectomy with electrocautery or the Ultrasonic Scalpel . Pain after tonsillectomy remains a major issue for our patients . The choice of surgical instrument appears to be one way to reduce this pain . EBM rating : OBJECTIVE To compare intraoperative efficiency and postoperative recovery between cold dissection adenotonsillectomy ( CDA ) and coblation-assisted adenotonsillectomy ( CAA ) . METHODS A prospect i ve , r and omized , single-blind trial of pediatric patients aged 2 to 16 years undergoing adenotonsillectomy was conducted . Patients were r and omized to undergo either CDA or CAA . Measured intraoperative parameters included surgical duration and intraoperative blood loss . Measured postoperative parameters included a 14 day caregiver question naire that recorded a daily pain rating using the Wong-Baker FACES pain scale , pain medication use , days to return to a normal diet , and days to return to a normal caregiver routine . Postoperative complications were also recorded . Intraoperative and postoperative measures were statistically compared between groups . RESULTS Forty-six children with a mean age of 6.7 years ( 23 CDA and 23 CAA ) were r and omized and completed the study . Mean age and sex distributions were similar between groups ( P > .05 ) . Surgical times were significantly shorter for the CAA group versus the CDA group ( 11.2 min vs. 17.0 min , P < .001 ) . Intraoperative blood loss was statistically lower for both the adenoidectomy and tonsillectomy portions of the procedure for the CAA group versus the CDA group ( P < .001 and P < .001 , respectively ) . There was no statistically significant difference in reported daily pain scores between groups ( P = .296 , analysis of variance ) . Both groups returned to normal diet ( P = .982 ) , and caregivers returned to their normal routine on similar postoperative days ( P = .631 ) . CONCLUSIONS CAA offers better operative speed and intraoperative hemostasis as compared with CDA . However , CAA does not result in poorer postoperative pain scores or recoveries despite these intraoperative advantages OBJECTIVE : We previously compared radiofrequency ( Evac ) tonsillotomy with monopolar electrosurgical ( Bovie ) tonsillectomy and showed significantly less pain with the Evac . Tonsillotomy leaves a cuff of tonsil behind , the significance of which is unknown . We hypothesize that Evac tonsillectomy also is less painful than Bovie tonsillectomy . STUDY DESIGN AND SETTING : We compared Evac ( ENTec Evac 70 ; ArthroCare , Sunnyvale , CA ) and Bovie tonsillectomy in a prospect i ve , blinded fashion . Each participant had 1 tonsil removed by each device . We recorded , by side , the surgical time , blood loss , operative difficulty , pain ( postoperative days 1 , 3 , 5 , 7 , 10 , and 14 ) , and the side that each patient preferred . RESULTS : Data were analyzed for 17 patients . They reported significantly less pain with the Evac ( P < 0.036 , F = 5.87 ) . The Evac was preferred by 12 of 14 patients . CONCLUSION : Evac tonsillectomy is significantly less painful than Bovie tonsillectomy . Patients blinded to treatment preferred the Evac technique . SIGNIFICANCE : The Evac device decreases postoperative pain This double-blind r and omized controlled trial of coblation tonsillotomy versus coblation tonsillectomy uses visual analogue scoring to compare the pain experienced in the 24h postoperative period . No statistically significant difference in pain is demonstrated in the group of 14 patients studied . Tonsillectomy is recommended over tonsillotomy OBJECTIVE : To compare the postoperative recovery of patients receiving Coblation-assisted ( Arthrocare , Sunnyvale , CA ) intracapsular tonsillectomy with that of patients receiving traditional subcapsular electrocautery tonsillectomy . STUDY DESIGN AND SETTING : This was a prospect i ve , r and omized , double-blinded , controlled study . One hundred one children , aged 2 to 16 years , were r and omized to Coblation or to conventional electrocautery tonsillectomy . Only patients with the operative indication of obstructive sleep apnea were entered into the study . Intracapsular tonsillectomy was performed on the Coblation group , and traditional subcapsular dissection was performed on the electrocautery group . Adenoidectomy was performed with the curette in both groups . Outcome measures were assessed on days 1 , 3 , and 5 after surgery . These included child and parental rating of pain by using the Wong Faces pain scale , analgesic use , oral intake , and activity level . Patients , parents , and the nurse practitioner obtaining the outcome data were blinded to treatment arm . RESULTS : Treatment groups were similar in age , gender , and weight . Surgical time and estimated blood loss were similar . There were no complications in either group . Coblation patients had less pain and greater oral intake at all 3 time points . Percentage of normal activity level returned to > 70 % earlier and more frequently in Coblation patients . There was slightly decreased analgesic use on postoperative day 5 in the Coblation group . CONCLUSIONS AND SIGNIFICANCE : Children with obstructive sleep apnea undergoing tonsillectomy and adenoidectomy demonstrate significantly better postoperative recovery after Coblation-assisted intracapsular tonsillectomy Background : Diclofenac is widely used for postoperative analgesia but the perioperative safety of this drug is controversial because of its effect on platelet aggregation , which might increase blood loss . In a prospect i ve investigator‐blinded study the effects of diclofenac and paracetamol on pain and blood loss were compared in patients undergoing tonsillectomy Adeno-tonsillectomy and tonsillectomy are frequently performed and haemorrhage remains an important post-operative complication . A prospect i ve study of 1090 patients undergoing surgery over a 12-month period was undertaken investigating whether the following factors influenced post-operative haemorrhage : age and sex of patients , method of tonsillectomy , haemostasis and premedication , month of operation and experience of surgeon . A significantly higher incidence of post-operative haemorrhage occurred in the group aged 16 - 25 years and significantly more males suffered post-operative haemorrhage . This haemorrhage more frequently occurred in the warmer months of May to July . Guillotine tonsillectomy was found to be as effective as dissection and no higher incidence of post-operative haemorrhage was recorded . Method of haemostasis , surgical experience and premedication did not influence the outcome . We conclude that the guillotine used in controlled circumstances is as safe as dissection BACKGROUND The introduction of coblation tonsillectomy ( CTE ) may contribute to reduce the postoperative morbidity in terms of pain , delayed oral intake and bleeding . METHODS A prospect i ve pilot study was undertaken to evaluate the clinical course by inpatient observation ( 5 days ) and telephone contact 6 months after CTE . The data from 61 patients ( aged 44 months-69 years ) were analyzed . The patients were grouped into those with surgical care of bleeding ( A ) , non-surgical care of bleeding ( B ) , and no bleeding event ( C ) . RESULTS The study was terminated early due to major bleeding complications in seven patients ( A ) . Fifteen patients experienced minor ( B ) and 41 no ( C ) bleeding episodes . In the interview , 29 patients identified pain , lasting 16.7 ( A ) , 11.6 ( B ) and 11 ( C ) days , as the most significant complication of surgery . CONCLUSIONS The introduction of CTE was followed by a dramatic increase in major bleeding complications , including late bleeding episodes . Pain following tonsillectomy remains a problem to be solved by further techniques . We will continue to perform the cold dissection technique |
785 | 28,795,243 | Conclusions Laparoscopic surgery for rectal cancer is associated with similar short-term and long-term oncologic outcomes compared to open surgery .
The oncologic quality of extracted specimens seems comparable regardless of the approach used | Abstract Background Until recently there has been little data available about long-term outcomes of laparoscopic rectal cancer surgery .
But new r and omized controlled trials regarding laparoscopic colorectal surgery have been published .
The aim of this study was to compare the short- and long-term oncologic outcomes of laparoscopy and open surgery for rectal cancer through a systematic review of the literature and a meta- analysis of relevant RCTs . | BACKGROUND Laparoscopic surgery as an alternative to open surgery in patients with rectal cancer has not yet been shown to be oncologically safe . The aim in the COlorectal cancer Laparoscopic or Open Resection ( COLOR II ) trial was to compare laparoscopic and open surgery in patients with rectal cancer . METHODS A non-inferiority phase 3 trial was undertaken at 30 centres and hospitals in eight countries . Patients ( aged ≥18 years ) with rectal cancer within 15 cm from the anal verge without evidence of distant metastases were r and omly assigned to either laparoscopic or open surgery in a 2:1 ratio , stratified by centre , location of tumour , and preoperative radiotherapy . The study was not masked . Secondary ( short-term ) outcomes -including operative findings , complications , mortality , and results at pathological examination-are reported here . Analysis was by modified intention to treat , excluding those patients with post-r and omisation exclusion criteria and for whom data were not available . This study is registered with Clinical Trials.gov , number NCT00297791 . FINDINGS The study was undertaken between Jan 20 , 2004 , and May 4 , 2010 . 1103 patients were r and omly assigned to the laparoscopic ( n=739 ) and open surgery groups ( n=364 ) , and 1044 were eligible for analyses ( 699 and 345 , respectively ) . Patients in the laparoscopic surgery group lost less blood than did those in the open surgery group ( median 200 mL [ IQR 100 - 400 ] vs 400 mL [ 200 - 700 ] , p<0·0001 ) ; however , laparoscopic procedures took longer ( 240 min [ 184 - 300 ] vs 188 min [ 150 - 240 ] ; p<0·0001 ) . In the laparoscopic surgery group , bowel function returned sooner ( 2·0 days [ 1·0 - 3·0 ] vs 3·0 days [ 2·0 - 4·0 ] ; p<0·0001 ) and hospital stay was shorter ( 8·0 days [ 6·0 - 13·0 ] vs 9·0 days [ 7·0 - 14·0 ] ; p=0·036 ) . Macroscopically , completeness of the resection was not different between groups ( 589 [ 88 % ] of 666 vs 303 [ 92 % ] of 331 ; p=0·250 ) . Positive circumferential resection margin ( < 2 mm ) was noted in 56 ( 10 % ) of 588 patients in the laparoscopic surgery group and 30 ( 10 % ) of 300 in the open surgery group ( p=0·850 ) . Median tumour distance to distal resection margin did not differ significantly between the groups ( 3·0 cm [ IQR 2·0 - 4·8 ] vs 3·0 cm [ 1·8 - 5·0 ] , respectively ; p=0·676 ) . In the laparoscopic and open surgery groups , morbidity ( 278 [ 40 % ] of 697 vs 128 [ 37 % ] of 345 , respectively ; p=0·424 ) and mortality ( eight [ 1 % ] of 699 vs six [ 2 % ] of 345 , respectively ; p=0·409 ) within 28 days after surgery were similar . INTERPRETATION In selected patients with rectal cancer treated by skilled surgeons , laparoscopic surgery result ed in similar safety , resection margins , and completeness of resection to that of open surgery , and recovery was improved after laparoscopic surgery . Results for the primary endpoint-locoregional recurrence-are expected by the end of 2013 . FUNDING Ethicon Endo-Surgery Europe , Swedish Cancer Foundation , West Gothia Region , Sahlgrenska University Hospital Introduction Total mesorectal excision ( TME ) is an essential component of surgical management of rectal cancer . Both open and laparoscopic TME have been proven to be oncologically safe . However , it remains a challenge to achieve complete TME with clear circumferential resections margin ( CRM ) with the conventional transabdominal approach , particularly in mid and low rectal tumours . Transanal TME ( TaTME ) was developed to improve oncological and functional outcomes of patients with mid and low rectal cancer . Methods An international , multicentre , superiority , r and omised trial was design ed to compare TaTME and conventional laparoscopic TME as the surgical treatment of mid and low rectal carcinomas . The primary endpoint is involved CRM . Secondary endpoints include completeness of mesorectum , residual mesorectum , morbidity and mortality , local recurrence , disease-free and overall survival , percentage of sphincter-saving procedures , functional outcome and quality of life . A Quality Assurance Protocol including central ised MRI review , histopathology re-evaluation , st and ardisation of surgical techniques , and monitoring and assessment of surgical quality will be conducted . Discussion The difference in involvement of CRM between the two treatment strategies is thought to be in favour of the TaTME . TaTME is therefore expected to be superior to laparoscopic TME in terms of oncological outcomes in case of mid and low rectal carcinomas Circumferential resection margin ( CRM ) appears as a new powerful prognostic factor of survival after surgery for rectal cancer . We aim ed to evaluate predictive factors of positive CRM following preoperative radiochemotherapy in a French trial . Patients with rectal cancer were r and omised in long course preoperative radiotherapy 45 Gy plus capecitabine versus 50 Gy plus capecitabine and oxaliplatin . Mesorectal excision was performed 6 weeks after treatment . Impact of clinical , pathological and surgical variables on positive CRM ( ≤1 mm ) were analysed by multivariate analysis . Of 565 r and omised patients , CRM was recorded in 390 cases and was positive in 8 % ( 30/390 ) . Patients with 50 Gy plus capecitabine and oxaliplatin had a 6 % rate of positive CRM while those treated by 45 Gy plus capecitabine had a 10 % rate ( p=0.128 ) . Three independent predictive factors of positive CRM were identified : abdominoperineal resection ( APR ) ( odds ratio OR=3.24 ; p=0.004 ) , vascular tumour invasion ( OR=2.78 ; p=0.026 ) and poor histological response ( modified Dworak 0 - 2 ) ( OR=9.01 ; p=0.003 ) . Significant predictive factors of positive CRM are related to type of surgery , especially APR , and poor histological prognostic factors . Intensification of neoadjuvant radiochemotherapy does not seem to have a major role in this study Background : The aim of the study was to evaluate quality of life ( QOL ) outcomes after colorectal surgery for cancer from a 6-month perspective at a single institution . Methods : Cohort study to prospect ively assess postoperative QOL in patients who underwent elective colorectal resection at the University Hospital Ostrava . QOL was assessed using the vali date d Short Form 36 ( SF-36v2 ™ ) question naire at fixed time points . Results : A total of 148 patients were enrolled in the study ( 83 and 65 patients underwent laparoscopic and open colorectal resection , respectively ) . Operative time was significantly longer ( 161 vs. 133 min ; p = 0.0073 ) and length of hospital stay was significantly shorter ( 10.7 vs. 13.1 days ; p = 0.0451 ) in the laparoscopic group . Overall 30-day morbidity rates were lower in the laparoscopic group , but the difference was not significant ( 27.7 vs. 33.8 % ; p = 0.2116 ) . QOL scores were comparable in both study groups before surgery ( p ≥ 0.05 ) . QOL was statistically significantly lower 2 days and 1 week after open colorectal surgery compared with laparoscopic surgery . One month and 6 months after surgery , there were no statistically significant differences between groups . Conclusion : The present study suggests a higher postoperative QOL during the first month after laparoscopic colorectal resection could be one of the benefits of laparoscopy BACKGROUND Laparoscopic resection of colorectal cancer is widely used . However , robust evidence to conclude that laparoscopic surgery and open surgery have similar outcomes in rectal cancer is lacking . A trial was design ed to compare 3-year rates of cancer recurrence in the pelvic or perineal area ( locoregional recurrence ) and survival after laparoscopic and open resection of rectal cancer . METHODS In this international trial conducted in 30 hospitals , we r and omly assigned patients with a solitary adenocarcinoma of the rectum within 15 cm of the anal verge , not invading adjacent tissues , and without distant metastases to undergo either laparoscopic or open surgery in a 2:1 ratio . The primary end point was locoregional recurrence 3 years after the index surgery . Secondary end points included disease-free and overall survival . RESULTS A total of 1044 patients were included ( 699 in the laparoscopic-surgery group and 345 in the open-surgery group ) . At 3 years , the locoregional recurrence rate was 5.0 % in the two groups ( difference , 0 percentage points ; 90 % confidence interval [ CI ] , -2.6 to 2.6 ) . Disease-free survival rates were 74.8 % in the laparoscopic-surgery group and 70.8 % in the open-surgery group ( difference , 4.0 percentage points ; 95 % CI , -1.9 to 9.9 ) . Overall survival rates were 86.7 % in the laparoscopic-surgery group and 83.6 % in the open-surgery group ( difference , 3.1 percentage points ; 95 % CI , -1.6 to 7.8 ) . CONCLUSIONS Laparoscopic surgery in patients with rectal cancer was associated with rates of locoregional recurrence and disease-free and overall survival similar to those for open surgery . ( Funded by Ethicon Endo-Surgery Europe and others ; COLOR II Clinical Trials.gov number , NCT00297791 . ) Purpose This study was design ed to evaluate the impact of laparoscopic rectal resection on short-term postoperative morbidity and costs . Methods A total of 168 patients with rectal cancer were r and omly assigned to laparoscopic ( n = 83 ) or open ( n = 85 ) resection . Outcome parameters were : postoperative morbidity , length of hospital stay , quality of life , long-term survival , and local recurrences . The mean follow-up period was 53.6 months . Cost-benefit analysis was based on hospital costs . Results Operative time was 53 minutes longer in the laparoscopic group ( P < 0.0001 ) . Postoperative morbidity rate was 28.9 percent in the laparoscopic vs. 40 percent in the open group ( P = 0.18 ) . The mean length of hospital stay was 10 ( 4.9 ) days in the laparoscopic group and 13.6 ( 10 ) days in the open group ( P = 0.004 ) . Local recurrence rate and five-year survival were similar in both groups ; however , the limited number of patients does not allow firm conclusions . Quality of life was better in the laparoscopic group only in the first year after surgery ( P < 0.0001 ) . The additional charge in the laparoscopic group was $ 1,748 per patient r and omized ( $ 1,194 the result of surgical instruments and $ 554 the result of longer operative time ) . The saving in the laparoscopic group was $ 1,396 per patient r and omized ( $ 647 the result of shorter length of hospital stay and $ 749 the result of the lower cost of postoperative complications ) . The net balance result ed in $ 351 extra cost per patient r and omly allocated to the laparoscopic group . Conclusions Short-term postoperative morbidity was similar in the two groups . Laparoscopic resection reduced length of hospital stay , improved first-year quality of life , and slightly increased hospital costs IMPORTANCE Evidence about the efficacy of laparoscopic resection of rectal cancer is incomplete , particularly for patients with more advanced-stage disease . OBJECTIVE To determine whether laparoscopic resection is noninferior to open resection , as determined by gross pathologic and histologic evaluation of the resected proctectomy specimen . DESIGN , SETTING , AND PARTICIPANTS A multicenter , balanced , noninferiority , r and omized trial enrolled patients between October 2008 and September 2013 . The trial was conducted by credentialed surgeons from 35 institutions in the United States and Canada . A total of 486 patients with clinical stage II or III rectal cancer within 12 cm of the anal verge were r and omized after completion of neoadjuvant therapy to laparoscopic or open resection . INTERVENTIONS St and ard laparoscopic and open approaches were performed by the credentialed surgeons . MAIN OUTCOMES AND MEASURES The primary outcome assessing efficacy was a composite of circumferential radial margin greater than 1 mm , distal margin without tumor , and completeness of total mesorectal excision . A 6 % noninferiority margin was chosen according to clinical relevance estimation . RESULTS Two hundred forty patients with laparoscopic resection and 222 with open resection were evaluable for analysis of the 486 enrolled . Successful resection occurred in 81.7 % of laparoscopic resection cases ( 95 % CI , 76.8%-86.6 % ) and 86.9 % of open resection cases ( 95 % CI , 82.5%-91.4 % ) and did not support noninferiority ( difference , -5.3 % ; 1-sided 95 % CI , -10.8 % to ∞ ; P for noninferiority = .41 ) . Patients underwent low anterior resection ( 76.7 % ) or abdominoperineal resection ( 23.3 % ) . Conversion to open resection occurred in 11.3 % of patients . Operative time was significantly longer for laparoscopic resection ( mean , 266.2 vs 220.6 minutes ; mean difference , 45.5 minutes ; 95 % CI , 27.7 - 63.4 ; P < .001 ) . Length of stay ( 7.3 vs 7.0 days ; mean difference , 0.3 days ; 95 % CI , -0.6 to 1.1 ) , readmission within 30 days ( 3.3 % vs 4.1 % ; difference , -0.7 % ; 95 % CI , -4.2 % to 2.7 % ) , and severe complications ( 22.5 % vs 22.1 % ; difference , 0.4 % ; 95 % CI , -4.2 % to 2.7 % ) did not differ significantly . Quality of the total mesorectal excision specimen in 462 operated and analyzed surgeries was complete ( 77 % ) and nearly complete ( 16.5 % ) in 93.5 % of the cases . Negative circumferential radial margin was observed in 90 % of the overall group ( 87.9 % laparoscopic resection and 92.3 % open resection ; P = .11 ) . Distal margin result was negative in more than 98 % of patients irrespective of type of surgery ( P = .91 ) . CONCLUSIONS AND RELEVANCE Among patients with stage II or III rectal cancer , the use of laparoscopic resection compared with open resection failed to meet the criterion for noninferiority for pathologic outcomes . Pending clinical oncologic outcomes , the findings do not support the use of laparoscopic resection in these patients . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00726622 Purpose This study was design ed to evaluate the impact of laparoscopic converted to open colectomy on short-term and oncologic outcomes and to identify risk factors for long-term survival in patients undergoing colectomy for non-metastatic colon cancer . Methods A prospect i ve data base of consecutive operations for non-metastatic colon cancer was review ed . Patients were grouped as conversion ( CONV ) group , completed laparoscopic resection ( LAP ) group , or open resection ( OPEN ) group . The clinical and perioperative parameters , pathologic features , and oncologic outcomes were collected . Univariate analysis was performed for comparing these data . Patients without evidence of recurrence at last follow-up or still alive at the end of study period were censored . Kaplan-Meier curves were utilized to analyze survival . A multivariate analysis was performed to identify predictors of poor disease-free survival ( DFS ) and overall survival ( OS ) . Results The conversion rate was 15.2 % . The most common reason for conversion was locally advanced cancer ( 45.5 % ) . Converted patients were associated with a longer operative time ( 188 ± 29.1 min , P < 0.001 ) , greater blood loss ( 147 ± 14 mL , P < 0.001 ) , and a higher rate of intra-operative complications ( 15.2 % , P = 0.042 ) compared to the completely laparoscopic or open patients . Days to flatus , early ambulation , and length of hospitalization were significantly shorter in completed laparoscopic resection ( LAP ) group ( P < 0.001 ) ; however , the outcomes were comparable between conversion ( CONV ) and open resection ( OPEN ) groups . The incidence of wound infection was significantly higher in the OPEN group than in the LAP group ( P = 0.005 ) , whereas there were no significant differences observed between the CONV group and the OPEN group ( P = 1.000 ) or between the LAP group and the CONV group ( P = 0.073 ) . The 5-year DFS in CONV patients ( 46.5 % ) was comparable to LAP patients ( 55.5 % , P = 0.138 ) and OPEN patients ( 59.1 % , P = 0.113 ) . Moreover , there were no significant differences noted in terms of the 5-year OS in the CONV group ( 56.7 % ) compared to the LAP group ( 67.3 % , P = 0.317 ) or the OPEN group ( 66.3 % , P = 0.420 ) . The multivariate analysis showed that pT3–4 cancer ( P < 0.001 ) and poor differentiation ( P < 0.001 ) were independent predictors of both lower OS and lower DFS , whereas leakage ( P = 0.008 ) and lack of adjuvant chemotherapy ( P = 0.023 ) were independent risk factors only of lower DFS . Conclusion Conversion to open colectomy from an initial laparoscopic approach does not worsen the long-term survival in patients with non-metastatic colon cancer Background A multicenter r and omized study is high quality , but it is also true that there are differences between institutions . The quality of treatment is consistent in a single center so comparisons in a retrospective study can be matched for many variables . Methods This single-center study examined short-term and long-term outcomes for colorectal cancer in 258 patients who underwent laparoscopic resection ( LC ) and 258 matched open resection ( OC ) cases . The health-related qualities of life ( HRQOL ) at 1–2 years after the operations in 62 patients ( 35 LC and 27 OC ) were compared by SF-36 . Results The conversion rate was 5.0 % . Mean follow-up periods in LC and OC were 62.3 and 62.1 months , respectively . Operation time was longer in LC than in OC , although the difference was not significant in the later period . Bleeding and postoperative stay were reduced in LC . The morbidity rate was 18.6 % in LC and 26.4 % in OC . The 5-year overall survival in LC and OC were 94.6 % vs. 92.0 % for stage I , 95.2 % vs. 91.8 % for stage II , and 80.9 % vs. 79.1 % for stage III , respectively . The corresponding 5-year disease-free survival were 94.0 % vs. 88.4 % , 92.1 % vs. 84.0 % , and 64.3 % vs. 65.4 % , respectively . Recurrence rates did not differ between groups . In the analysis of HRQOL scores , role physical , bodily pain , social functioning , role emotional , and physical component summary scores in LC were better than in OC . Conclusions In LC for colorectal cancer , short-term outcomes except operation time and mid-term HRQOL were better than in OC , and there were no adverse effects relating to long-term outcomes Despite improved surgical treatment strategies for rectal cancer , 5–15 % of all patients will develop local recurrences . After conservative surgery , circumferential resection margin ( CRM ) involvement is a strong predictor of local recurrence . The consequences of a positive CRM after total mesorectal excision ( TME ) have not been evaluated in a large patient population . In a nationwide r and omized multicenter trial comparing preoperative radiotherapy and TME versus TME alone for rectal cancer , CRM involvement was determined according to trial protocol . In this study we analyze the criteria by which the CRM needs to be assessed to predict local recurrence for nonirradiated patients ( n = 656 , median follow-up 35 months ) . CRM involvement is a strong predictor for local recurrence after TME . A margin of ≤2 mm is associated with a local recurrence risk of 16 % compared with 5.8 % in patients with more mesorectal tissue surrounding the tumor ( p < 0.0001 ) . In addition , patients with margins ≤1 mm have an increased risk for distant metastases ( 37.6 % vs 12.7 % , p < 0.0001 ) as well as shorter survival . The prognostic value of CRM involvement is independent of TNM classification . Accurate determination of CRM in rectal cancer is important for determination of local recurrence risk , which might subsequently be prevented by additional therapy . In contrast to earlier studies , we show that an increased risk is present when margins are ≤2 mm Lymph node status is the strongest prognostic factor for survival in colorectal cancer . There are several guidelines concerning the minimum numbers of lymph nodes that need to be examined to make reliable staging possible , but there is no consensus in the available literature . In this study , we determine in patients with rectal cancer factors that relate to the number of lymph nodes found and the presence of lymph node metastasis . In addition , the number of examined lymph nodes was correlated with prognosis . A total of 1227 patients were selected from a multicenter prospect i ve r and omized trial investigating the value of neoadjuvant radiotherapy . The median number of examined lymph nodes in all patients was 7.0 . The number of retrieved lymph nodes in patients with node metastasis was significantly higher than in node negative patients . After neoadjuvant radiotherapy fewer lymph nodes were retrieved ( 6.9 vs. 8.5 ; P<0.0001 ) . Variations in lymph node yield between pathology laboratories and individual pathologists were striking . The following patient and tumor characteristics are associated with a significant lower lymph node retrieval : age over 60 years , overweight , small size , and low invasion depth of the tumor , poor differentiation grade , and absence of a lymphoid reaction . Node negative patients in whom seven or less lymph nodes were examined had a lower recurrence free interval than patients in whom at least 8 lymph nodes were examined ( 17.0 % vs. 10.7 % , P=0.016 ) . We conclude that in pathology laboratories a median of at least 8 lymph nodes need to be examined in rectal cancer specimens , but that higher numbers are desirable and achievable in most cases , even after preoperative radiotherapy AIM To investigate the short-term outcome of laparoscopic total mesorectal excision ( TME ) in patients with mid and low rectal cancers . METHODS A consecutive series of 138 patients with middle and low rectal cancer were r and omly assigned to either the laparoscopic TME ( LTME ) group or the open TME ( OTME ) group between September 2008 and July 2011 at the Department of Colorectal Cancer of Shanghai Cancer Center , Fudan University and pathological data , as well as surgical technique were review ed retrospectively . Short-term clinical and oncological outcome were compared in these two groups . Patients were followed in the outpatient clinic 2 wk after the surgery and then every 3 mo in the first year if no adjuvant chemoradiation was indicated . Statistical analysis was performed using SPSS 13.0 software . RESULTS Sixty-seven patients were treated with LTME and 71 patients were treated with OTME ( sex ratio 1.3:1 vs 1.29:1 , age 58.4 ± 13.6 years vs 59.6 ± 9.4 years , respectively ) . The resection was considered curative in all cases . The sphincter-preserving rate was 65.7 % ( 44/67 ) vs 60.6 % ( 43/71 ) , P = 0.046 ; mean blood loss was 86.9 ± 37.6 mL vs 119.1 ± 32.7 mL , P = 0.018 ; postoperative analgesia was 2.1 ± 0.6 d vs 3.9 ± 1.8 d , P = 0.008 ; duration of urinary drainage was 4.7 ± 1.8 d vs 6.9 ± 3.4 d , P = 0.016 , respectively . The conversion rate was 2.99 % . The complication rate , circumferential margin involvement , distal margins and lymph node yield were similar for both procedures . No port site recurrence , anastomotic recurrence or mortality was observed during a median follow-up period of 21 mo ( range : 9 - 56 mo ) . CONCLUSION Laparoscopic TME is safe and feasible , with an oncological adequacy comparable to the open approach . Further studies with more patients and longer follow-up are needed to confirm the present results PURPOSE Quality assessment and assurance are important issues in modern health care . For the evaluation of surgical procedures , there are indirect parameters such as complication , recurrence , and survival rates . These parameters are of limited value for the individual surgeon , and there is an obvious need for direct parameters . We have evaluated criteria by which pathologists can judge the quality or completeness of the resection specimen in a r and omized trial for rectal cancer . PATIENTS AND METHODS The pathology reports of all patients entered onto a Dutch multicenter r and omized trial were review ed . All participating pathologists had been instructed by workshops and videos in order to obtain st and ardized pathology work-up . A three-tiered classification was applied to assess completeness of the total mesorectal excision ( TME ) . Prognostic value of this classification was tested using log-rank analysis of Kaplan-Meier survival curves using the data of all patients who did not receive any adjuvant treatment . RESULTS Included were 180 patients . In 24 % ( n = 43 ) , the mesorectum was incomplete . Patients in this group had an increased risk for local and distant recurrence , 36.1 % v. 20.3 % recurrence in the group with a complete mesorectum ( P = .02 ) . Follow-up is too short to observe an effect on survival rates . CONCLUSION A patient 's prognosis is predicted by applying a classification of macroscopic completeness on a rectal resection specimen . We conclude that pathologists are able to judge the quality of TME for rectal cancer . With this direct interdisciplinary assessment instrument , we establish a new role of the pathologist in quality control Background This single-center , prospect i ve , r and omized trial was design ed to compare the short-term clinical outcome between laparoscopic-assisted versus open total mesorectal excision ( TME ) with anal sphincter preservation ( ASP ) in patients with mid and low rectal cancer . Long-term morbidity and survival data also were recorded and compared between the two groups . Methods Between August 2001 and August 2007 , 80 patients with mid and low rectal cancer were r and omized to receive either laparoscopic-assisted ( 40 patients ) or open ( 40 patients ) TME with ASP . The median follow-up time for all patients was 75.7 ( range 16.9–115.7 ) months for the laparoscopic-assisted group and 76.1 ( range 4.7–126.6 ) months for the open group . The primary endpoint of the study was short-term clinical outcome . Secondary endpoints included long-term morbidity rate and survival . Data were analyzed by intention-to-treat principle . Results The demographic data of the two groups were comparable . Postoperative recovery was better after laparoscopic surgery , with less analgesic requirement ( P < 0.001 ) , earlier mobilization ( P = 0.001 ) , lower short-term morbidity rate ( P = 0.043 ) , and a trend towards shorter hospital stay ( P = 0.071 ) . The cumulative long-term morbidity rate also was lower in the laparoscopic-assisted group ( P = 0.019 ) . The oncologic clearance in terms of macroscopic quality of the TME specimen , circumferential resection margin involvement , and number of lymph nodes removed was similar between both groups . After curative resection , the probabilities of survival at 5 years of the laparoscopic-assisted and open groups were 85.9 and 91.3 % , respectively ( P = 0.912 ) . The respective probabilities of being disease-free were 83.3 and 74.5 % ( P = 0.114 ) . Conclusions Laparoscopic-assisted TME with ASP improves postoperative recovery , reduces short-term and long-term morbidity rates , and seemingly does not jeopardize survival compared with open surgery for mid and low rectal cancer ( http:// Clinical Trials.gov Identifier : NCT00485316 ) BACKGROUND The safety and short-term efficacy of laparoscopic surgery for rectal cancer after preoperative chemoradiotherapy has not been demonstrated . The aim of the r and omised Comparison of Open versus laparoscopic surgery for mid and low REctal cancer After Neoadjuvant chemoradiotherapy ( COREAN ) trial was to compare open surgery with laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy . METHODS Between April 4 , 2006 , and Aug 26 , 2009 , patients with cT3N0 - 2 mid or low rectal cancer without distant metastasis after preoperative chemoradiotherapy were enrolled at three tertiary-referral hospitals . Patients were r and omised 1:1 to receive either open surgery ( n=170 ) or laparoscopic surgery ( n=170 ) , stratified according to sex and preoperative chemotherapy regimen . Short-term outcomes assessed were involvement of the circumferential resection margin , macroscopic quality of the total mesorectal excision specimen , number of harvested lymph nodes , recovery of bowel function , perioperative morbidity , postoperative pain , and quality of life . Analyses were based on the intention-to-treat population . Patients continue to be followed up for the primary outcome ( 3-year disease-free survival ) . This study is registered with Clinical Trials.gov , number NCT00470951 . FINDINGS Two patients ( 1.2 % ) in the laparoscopic group were converted to open surgery , but were included in the laparoscopic group for analyses . Estimated blood loss was less in the laparoscopic group than in the open group ( median 217.5 mL [ 150.0 - 400.0 ] in the open group vs 200.0 mL [ 100.0 - 300.0 ] in the laparoscopic group , p=0.006 ) , although surgery time was longer in the laparoscopic group ( mean 244.9 min [ SD 75.4 ] vs 197.0 min [ 62.9 ] , p<0.0001 ) . Involvement of the circumferential resection margin , macroscopic quality of the total mesorectal excision specimen , number of harvested lymph nodes , and perioperative morbidity did not differ between the two groups . The laparoscopic surgery group showed earlier recovery of bowel function than the open surgery group ( time to pass first flatus , median 38.5 h [ 23.0 - 53.0 ] vs 60.0 h [ 43.0 - 73.0 ] , p<0.0001 ; time to resume a normal diet , 85.0 h [ 66.0 - 95.0 ] vs 93.0 h [ 86.0 - 121.0 ] , p<0.0001 ; time to first defecation , 96.5 h [ 70.0 - 125.0 ] vs 123 h [ 94.0 - 156.0 ] , p<0.0001 ) . The total amount of morphine used was less in the laparoscopic group than in the open group ( median 107.2 mg [ 80.0 - 150.0 ] vs 156.9 mg [ 117.0 - 185.2 ] , p<0.0001 ) . 3 months after proctectomy or ileostomy takedown , the laparoscopic group showed better physical functioning score than the open group ( 0.501 [ n=122 ] vs -4.970 [ n=128 ] , p=0.0073 ) , less fatigue ( -5.659 [ n=122 ] vs 0.098 [ n=129 ] , p=0.0206 ) , and fewer micturition ( -2.583 [ n=122 ] vs 4.725 [ n=129 ] , p=0.0002 ) , gastrointestinal ( -0.400 [ n=122 ] vs 4.331 [ n=129 ] , p=0.0102 ) , and defecation problems ( 0.535 [ n=103 ] vs 5.327 [ n=99 ] , p=0.0184 ) in repeated measures analysis of covariance , adjusted for baseline values . INTERPRETATION Laparoscopic surgery after preoperative chemoradiotherapy for mid or low rectal cancer is safe and has short-term benefits compared with open surgery ; the quality of oncological resection was equivalent IMPORTANCE Laparoscopic procedures are generally thought to have better outcomes than open procedures . Because of anatomical constraints , laparoscopic rectal resection may not be better because of limitations in performing an adequate cancer resection . OBJECTIVE To determine whether laparoscopic resection is noninferior to open rectal cancer resection for adequacy of cancer clearance . DESIGN , SETTING , AND PARTICIPANTS R and omized , noninferiority , phase 3 trial ( Australasian Laparoscopic Cancer of the Rectum ; ALaCaRT ) conducted between March 2010 and November 2014 . Twenty-six accredited surgeons from 24 sites in Australia and New Zeal and r and omized 475 patients with T1-T3 rectal adenocarcinoma less than 15 cm from the anal verge . INTERVENTIONS Open laparotomy and rectal resection ( n = 237 ) or laparoscopic rectal resection ( n = 238 ) . MAIN OUTCOMES AND MEASURES The primary end point was a composite of oncological factors indicating an adequate surgical resection , with a noninferiority boundary of Δ = -8 % . Successful resection was defined as meeting all the following criteria : ( 1 ) complete total mesorectal excision , ( 2 ) a clear circumferential margin ( ≥1 mm ) , and ( 3 ) a clear distal resection margin ( ≥1 mm ) . Pathologists used st and ardized reporting and were blinded to the method of surgery . RESULTS A successful resection was achieved in 194 patients ( 82 % ) in the laparoscopic surgery group and 208 patients ( 89 % ) in the open surgery group ( risk difference of -7.0 % [ 95 % CI , -12.4 % to ∞ ] ; P = .38 for noninferiority ) . The circumferential resection margin was clear in 222 patients ( 93 % ) in the laparoscopic surgery group and in 228 patients ( 97 % ) in the open surgery group ( risk difference of -3.7 % [ 95 % CI , -7.6 % to 0.1 % ] ; P = .06 ) , the distal margin was clear in 236 patients ( 99 % ) in the laparoscopic surgery group and in 234 patients ( 99 % ) in the open surgery group ( risk difference of -0.4 % [ 95 % CI , -1.8 % to 1.0 % ] ; P = .67 ) , and total mesorectal excision was complete in 206 patients ( 87 % ) in the laparoscopic surgery group and 216 patients ( 92 % ) in the open surgery group ( risk difference of -5.4 % [ 95 % CI , -10.9 % to 0.2 % ] ; P = .06 ) . The conversion rate from laparoscopic to open surgery was 9 % . CONCLUSIONS AND RELEVANCE Among patients with T1-T3 rectal tumors , noninferiority of laparoscopic surgery compared with open surgery for successful resection was not established . Although the overall quality of surgery was high , these findings do not provide sufficient evidence for the routine use of laparoscopic surgery . Longer follow-up of recurrence and survival is currently being acquired . TRIAL REGISTRATION anzctr.org Identifier : ACTRN12609000663257 BACKGROUND Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale r and omised trials to support its use . We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes . METHODS Between July , 1996 , and July , 2002 , we undertook a multicentre , r and omised clinical trial in 794 patients with colorectal cancer from 27 UK centres . Patients were allocated to receive laparoscopic-assisted ( n=526 ) or open surgery ( n=268 ) . Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins , proportion of Dukes ' C2 tumours , and in-hospital mortality . Analysis was by intention to treat . This trial has been assigned the International St and ard R and omised Controlled Trial Number IS RCT N74883561 . FINDINGS Six patients ( two [ open ] , four [ laparoscopic ] ) had no surgery , and 23 had missing surgical data ( nine , 14 ) . 253 and 484 patients actually received open and laparoscopic-assisted treatment , respectively . 143 ( 29 % ) patients underwent conversion from laparoscopic to open surgery . Proportion of Dukes ' C2 tumours did not differ between treatments ( 18 [ 7 % ] patients , open vs 34 [ 6 % ] , laparoscopic ; difference -0.3 % , 95 % CI -3.9 to 3.4 % , p=0.89 ) , and neither did in-hospital mortality ( 13 [ 5 % ] vs 21 [ 4 % ] ; -0.9 % , -3.9 to 2.2 % , p=0.57 ) . Apart from patients undergoing laparoscopic anterior resection for rectal cancer , rates of positive resection margins were similar between treatment groups . Patients with converted treatment had raised complication rates . INTERPRETATION Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes . However , impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use |
786 | 24,453,356 | It became apparent from our studies that both feeding strategies have advantages and disadvantages | There are two main enteral feeding strategies-namely nasogastric ( NG ) tube feeding and percutaneous gastrostomy-used to improve the nutritional status of patients with head and neck cancer ( HNC ) .
But up till now there has been no consistent evidence about which method of enteral feeding is the optimal method for this patient group . | BACKGROUND & AIMS A system for screening of nutritional risk is described . It is based on the concept that nutritional support is indicated in patients who are severely ill with increased nutritional requirements , or who are severely undernourished , or who have certain degrees of severity of disease in combination with certain degrees of undernutrition . Degrees of severity of disease and undernutrition were defined as absent , mild , moderate or severe from data sets in a selected number of r and omized controlled trials ( RCTs ) and converted to a numeric score . After completion , the screening system was vali date d against all published RCTs known to us of nutritional support vs spontaneous intake to investigate whether the screening system could distinguish between trials with a positive outcome and trials with no effect on outcome . METHODS The total number of r and omized trials identified was 128 . In each trial , the group of patients was classified with respect to nutritional status and severity of disease , and it was determined whether the effect of nutritional intervention on clinical outcome was positive or absent . RESULTS Among 75 studies of patients classified as being nutritionally at-risk , 43 showed a positive effect of nutritional support on clinical outcome . Among 53 studies of patients not considered to be nutritionally at-risk , 14 showed a positive effect ( P=0.0006 ) . This corresponded to a likelihood ratio ( true positive/false positive ) of 1.7 ( 95 % CI : 2.3 - 1.2 ) . For 71 studies of parenteral nutrition , the likelihood ratio was 1.4 ( 1.9 - 1.0 ) , and for 56 studies of enteral or oral nutrition the likelihood ratio was 2.9 ( 5.9 - 1.4 ) . CONCLUSION The screening system appears to be able to distinguish between trials with a positive effect vs no effect , and it can therefore probably also identify patients who are likely to benefit from nutritional support Abstract Wasting is a major complication of advanced head and neck cancer and the aim of this study was to compare nasogastric tube feeding ( NG ) and percutaneous fluoroscopic gastrostomy ( PFG ) in these patients . The goal of these two methods of nutritional support was to improve or maintain the initial nutritional status during treatment . A total of 90 patients , all stage IV oropharynx or hypopharynx tumor , were review ed from a prospect i ve data bank . All these patients were treated by concomitant chemotherapy and twice-daily continuous radiotherapy with no acceleration . Fifty patients were managed by PFG , and the rest by NG . Mechanical failure , duration of feeding , complications , nutritonal evaluation and quality of life were analysed . Mechanical failure occurred in 32 of the 40 NG patients and in seven of the gastrostomy group . In the PFG group , 80 % of patients conserved their nutritional support after the end of the radiotherapy , none patient in the NG group . In the PFG group , two presented a wound infection and six had aspiration pneumonia while in the NG group , 21 had aspiration pneumonia probably due to the NG tube ( gastroesophageal reflux ) . The feeding methods were found to be equally effective at maintaining body weight and body mass index at time 1 ( 3 weeks ) and at time 2 ( 6 weeks ) . Advantages were associated with PFG cosmesis , mobility and quality of life . PFG is a safe and effective method of providing enteral nutrition during treatment to patients with advanced head and neck cancer and offers important advantages over NG Malnutrition occurs frequently in patients with cancer of the gastrointestinal ( GI ) or head and neck area and can lead to negative outcomes . The aim of this study is to determine the impact of early and intensive nutrition intervention ( NI ) on body weight , body composition , nutritional status , global quality of life ( QoL ) and physical function compared to usual practice in oncology out patients receiving radiotherapy to the GI or head and neck area . Out patients commencing at least 20 fractions of radiotherapy to the GI or head and neck area were r and omised to receive intensive , individualised nutrition counselling by a dietitian using a st and ard protocol and oral supplements if required , or the usual practice of the centre ( general advice and nutrition booklet ) . Outcome parameters were measured at baseline and 4 , 8 and 12 weeks after commencing radiotherapy using valid and reliable tools . A total of 60 patients ( 51 M : 9F ; mean age 61.9±14.0 years ) were r and omised to receive either NI ( n=29 ) or usual care ( UC ) ( n=31 ) . The NI group had statistically smaller deteriorations in weight ( P<0.001 ) , nutritional status ( P=0.020 ) and global QoL ( P=0.009 ) compared with those receiving UC . Clinical ly , but not statistically significant differences in fat-free mass were observed between the groups ( P=0.195 ) . Early and intensive NI appears beneficial in terms of minimising weight loss , deterioration in nutritional status , global QoL and physical function in oncology out patients receiving radiotherapy to the GI or head and neck area . Weight maintenance in this population leads to beneficial outcomes and suggests that this , rather than weight gain , may be a more appropriate aim of NI Background Dysphagia occurs in up to 50 % of patients admitted to hospital with acute strokes with up to 27 % remaining by seven days . Up to 8 % continue to have swallowing problems six months after their stroke with 1.7 % still requiring enteral feeding . Nasogastric tubes ( NGT ) are the most commonly used method for providing enteral nutrition in early stroke , however they are easily and frequently removed leading to inadequate nutrition , early PEG ( Percutaneous Endoscopic Gastrostomy ) insertion or ab and oning of feeding attempts . Looped nasogastric tube feeding may improve the delivery of nutrition to such patients . Methods Three centre , two arm r and omised controlled trial , with 50 participants in each arm comparing loop ( the intervention ) versus conventional nasogastric tube feeding . The primary outcome measure is proportion of intended feed delivered in the first 2 weeks . The study is design ed to show a mean increase of feed delivery of 16 % in the intervention group as compared with the control group , with 90 % power at a 5 % significance level . Secondary outcomes are treatment failures , mean volume of feed received , adverse events , cost-effectiveness , number of chest x-rays , number of nasogastric tubes and tolerability . Trial Registration IS RCT N Number : IS RCT This is a prospect i ve case-control study to assess nutritional supplementation in limiting weight loss and its impact on daily set-up variations and planning target volume ( PTV ) margins in head and neck ( H&N ) radiotherapy ( RT ) . Twenty sequential H&N patients were recruited for this study . Ten patients had a percutaneous endoscopic gastrostomy ( PEG ) tube inserted prior to RT and 10 did not . PEG use was determined by departmental guidelines for patients considered at high risk for weight loss . Daily 2D electronic portal images were taken for orthogonal verification . Set-up variations were determined for both PEG and non-PEG patients by calculating systematic ( Sigma ) and r and om ( sigma ) errors , and PTV margins were derived . PEG patients lost less weight ( P = 0.04 ) over the course of RT and had a reduction in set-up variation in the superior-inferior ( SI ) and anterior-posterior ( AP ) planes compared to those without . Mean correctional shifts in mm ( range ) for PEG patients were : Right-Left ( RL ) 0.1 ( -1.9 - 2.1 ) , SI -1.7 ( -2.9 - 0.0 ) , AP -0.4 ( -2.0 - 0.8 ) , and for non-PEG patients were : RL -0.2 ( -2.7 - 1.3 ) , SI -1.3 ( -3.1 - 1.0 ) , AP 0.4 ( -1.5 - 2.8 ) . The adapted PTV margins ( mm ) in the RL , SI and AP planes , respectively , for PEG patients were 4.1 , 3.3 and 3.6 , and for non-PEG were 3.9 , 4.9 and 4.8 . Intensive enteral support maintained weight stability in H&N patients considered at risk of weight loss during RT and this was associated with reduced set-up variation OBJECTIVES /HYPOTHESIS Percutaneous endoscopic gastrostomy tube ( PEG ) placement by means of the " pull " method has been reported to result in a significantly higher complication rate when compared with " push " PEG placement . These findings have led to a renewed interest in the push , or Russell introducer , method of PEG placement at the authors ' institution when PEG is required before definitive treatment of advanced head and neck cancer . The authors sought to determine whether the push method of PEG placement is associated with a lower incidence of complications in this patient population . STUDY DESIGN Nonr and omized , retrospective patient analysis . METHODS The medical records of all patients presenting to the Medical College of Georgia ( Augusta , GA ) who received a diagnosis of squamous cell carcinoma of the head and neck between 1999 to 2001 were retrospectively review ed . Patients who required PEG placement as part of their treatment comprised the study population . RESULTS The push PEG technique was used in 29 patients , and the pull technique was used in 50 patients . There was a statistically significant difference in the complication rate between the two techniques . Patients who underwent placement by means of the pull technique had an overall complication rate of 30 % ( 15 of 50 ) versus a 0 % ( 0 of 29 ) complication rate in patients undergoing the push technique ( P = .0006 , Fisher 's Exact test ) . CONCLUSION The push PEG technique appears to have a significantly lower risk of complications compared with the pull technique in patients with advanced head and neck cancer . The authors recommend considering the use of the push method when PEG placement is required ABSTRACT To compare the efficacy of percutaneous endoscopic gastrostomy ( PEG ) and nasogastric ( NGT ) tube administration of enteral nutrition in head and neck cancer patients undergoing curative treatment , the authors conducted a prospect i ve study to compare nutritional outcomes , complications , and patient satisfaction . PEG patients sustained significantly less reduction in nutritional parameters , measured at 6 weeks post insertion , as compared with NGT patients . There was also a statistically significant difference between the two groups in patient 's quality of life scores and complications . Comparison could not be done at 6 months because all patients were converted to PEG feeding due to the earlier findings . The authors conclude that PEG is more efficacious than NGT as a channel for nutrition in advanced head and neck cancer patients over a short duration The aim of this prospect i ve two year study was to compare the outcome of two methods of nutritional support , namely nasogastric [ NG ] and percutaneous endoscopic gastrostomy [ PEG ] feeding implemented for head and neck cancer patients unable to maintain their nutritional status whilst receiving radiotherapy treatment at a regional oncology unit . The nutritional requirements of the 100 patients included in the study were calculated and an enteral feeding regime implemented to ensure the nutritional requirements of each individual patient were met . Any changes in the weight and body mass index [ BMI ] of each patient during the study period were documented . The method of delivery , composition of feed and duration of nutritional support of each feeding method were determined . The feeding methods were found to be equally effective at maintaining body weight . Patients with NG tubes in situ were more frequently prescribed a st and ard 1 kcal/ml feed administered via an enteral feeding pump , whereas patients with PEG tubes in situ were more frequently prescribed a high energy 1.5 Kcal/ ml feed administered by the bolus method . A number of advantages are associated with PEG feeding including greater mobility , cosmesis and quality of life . Evidence indicates the outcome of radiotherapy treatment is not as favourable if interrupted , therefore , it is essential PEG tubes are sited prior to commencing treatment , illustrating the necessity for dietetic intervention for every patient to be addressed and incorporated into the treatment plan on diagnosis of head and neck cancer before definitive management commences BACKGROUND Percutaneous endoscopic gastrostomy ( PEG ) tubes have largely replaced nasogastric tubes ( NGTs ) for nutritional support of patients with head and neck cancer undergoing curative ( chemo ) radiotherapy without any good scientific basis . METHODS A prospect i ve study was conducted to compare PEG tubes and NGTs in terms of nutritional outcomes , complications , patient satisfaction , and cost . RESULTS There were 32 PEG and 73 NGT patients . PEG patients sustained significantly less weight loss at 6 weeks post-treatment ( median 0.8 kg gain vs 3.7 kg loss , p < .001 ) , but had a high insertion site infection rate ( 41 % ) , longer median duration of use ( 146 vs 57 days , p < .001 ) , and more grade 3 dysphagia in disease-free survivors at 6 months ( 25 % vs 8 % , p = .07 ) . Patient self-assessed general physical condition and overall quality of life scores were similar in both groups . Overall costs were significantly higher for PEG patients . CONCLUSION PEG tube use should be selective , not routine , in this patient population BACKGROUND AND STUDY AIMS Infection of the gastrostomy opening after placement of a percutaneous endoscopic gastrostomy ( PEG ) catheter has been reported to occur quite often , especially when the pull method is used . We therefore compared complications occurring with the pull and push methods , and evaluated the role of antibiotic prophylaxis . PATIENTS AND METHODS In a prospect i ve study , 100 consecutive patients were r and omly assigned to group A ( pull plus antibiotic prophylaxis : amoxycillin-clavulanic acid 3 x 1.2 g i.v . over 24 hours ; 37 patients ) , group B ( pull without antibiotic prophylaxis ; 34 patients ) and group C ( push without antibiotic prophylaxis ; 29 patients ) . The indications for PEG placement were dysphagia due to oropharyngeal tumors ( 56 % ) , neurological disease ( 32 % ) , or other ( 12 % ) . Patients were evaluated twice weekly for one month after the PEG placement . RESULTS PEG catheters were successfully placed in 96 % of the patients . The total procedure-related complication rate was significantly lower in group A than in groups B and C ( 28 % , 58 % , and 70 % , respectively ; p < 0.01 ) . Major complications occurred in one patient in group A ( seeding metastasis of a hypopharyngeal carcinoma in the gastrostomy tract ) , and in four patients in group B ( three cases of peritonitis and one aspiration , result ing in two deaths ) , but in none of the group C patients . Group A patients experienced fewer peristomal infections than the other two groups ( 14 % , 30 % , and 41 % , respectively : p = 0.05 ) . The risk of peristomal pain was similar ( 11 % , 15 % , and 11 % , respectively ; p = n.s . ) . In three patients in group C , the PEG catheter had to be replaced by the pull method , due to repeated dislocation of the balloon catheter . CONCLUSIONS The complication rate with PEG placement is high with both the push and pull methods . The complication rate with the pull method is significantly reduced when antibiotic prophylaxis is used OBJECTIVES In a prospect i ve clinical study , we tested the hypothesis that sparing the parotid gl and s may result in significant objective and subjective improvement of xerostomia in patients with head- and -neck cancers . The functional outcome 6 months after the completion of radiation therapy is presented . METHODS AND MATERIAL S From February 1997 to February 1999 , 41 patients with head- and -neck cancers were enrolled in a prospect i ve salivary function study . Inverse-planning intensity-modulated radiation therapy ( IMRT ) was used to treat 27 patients , and forward-planning three-dimensional radiation therapy in 14 . To avoid potential bias in data interpretation , only patients whose subm and ibular gl and s received greater than 50 Gy were eligible . Attempts were made to spare the superficial lobe of the parotid gl and s to avoid underdosing tumor targets in the parapharyngeal space ; however , the entire parotid volume was used to compute dose-volume histograms ( DVHs ) for this analysis . DVHs were computed for each gl and separately . Parotid function was assessed objective ly by measuring stimulated and unstimulated saliva flow before and 6 months after the completion of radiation therapy . Measurements were converted to flow rate ( mL/min ) and normalized relative to that before treatment . The corresponding quality -of-life ( QOL ) outcome was assessed by five questions regarding the patient 's oral discomfort and eating/speaking problems . RESULTS We observed a correlation between parotid mean dose and the fractional reduction of stimulated saliva output at 6 months after the completion of radiation therapy . We further examined whether the functional outcome could be modeled as a function of dose . Two models were found to describe the dose-response data well . The first model assumed that each parotid gl and is comprised of multiple independent parallel functional subunits ( corresponding to computed tomography voxels ) and that each gl and contributes equally to overall flow , and that saliva output decreases exponentially as a quadratic function of irradiation dose to each voxel . The second approach uses the equivalent uniform dose ( EUD ) metrics , which assumes loss of salivary function with increase in EUD for each parotid gl and independently . The analysis suggested that the mean dose to each parotid gl and is a reasonable indicator for the functional outcome of each gl and . The corresponding exponential coefficient was 0.0428/Gy ( 95 % confidence interval : 0.01 , 0.09 ) . The QOL questions on eating/speaking function were significantly correlated with stimulated and unstimulated saliva flow at 6 months . In a multivariate analysis , a toxicity score derived from the model based on radiation dose to the parotid gl and was found to be the sole significant predictive factor for xerostomia . Neither radiation technique ( IMRT vs. non-IMRT ) nor chemotherapy ( yes or no ) independently influenced the functional outcome of the salivary gl and s. CONCLUSION Sparing of the parotid gl and s translates into objective and subjective improvement of both xerostomia and QOL scores in patients with head- and -neck cancers receiving radiation therapy . Modeling results suggest an exponential relationship between saliva flow reduction and mean parotid dose for each gl and . We found that the stimulated saliva flow at 6 months after treatment is reduced exponentially , for each gl and independently , at a rate of approximately 4 % per Gy of mean parotid dose |
787 | 23,076,949 | There is little robust evidence to suggest that unintended consequences ( such as youth making false cl aims about their smoking status and bullying of smoking students ) are consistently associated with such interventions , although this has not been the focus of much research . | BACKGROUND Adult smoking usually has its roots in adolescence .
If individuals do not take up smoking during this period it is unlikely that they ever will .
Further , once smoking becomes established , cessation is challenging ; the probability of subsequently quitting is inversely proportional to the age of initiation .
One novel approach to reducing the prevalence of youth smoking is the use of incentives .
OBJECTIVES To determine whether incentives prevent children and adolescents from starting to smoke .
We also attempted to assess the dose-response of incentives , the costs of incentive programmes , whether incentives are more or less effective in combination with other interventions to prevent smoking initiation and any unintended consequences arising from the use of incentives . | Reports of cluster r and omised trials require additional information to allow readers to interpret them accurately The effective reporting of r and omised controlled trials has received useful attention in recent years . Many journals now require that reports conform to the guidelines in the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement , first published in 1996 and revised in 2001 . The statement includes a checklist of items that should be included in the trial report . These items are evidence based whenever possible and are regularly review ed . The statement also recommends including a flow diagram to show the flow of participants from group assignment through to the final analysis . The CONSORT statement focused on reporting parallel group r and omised trials in which individual participants are r and omly assigned to study groups . However , in some situations it is preferable to r and omly assign groups of individuals ( such as families or medical practice s ) rather than individuals . Reasons include the threat of contamination of some interventions ( such as dietary interventions ) if individual r and omisation is used . 5 Also , in certain setting s r and omisation by group may be the only feasible method of conducting a trial . Trials with this design are variously known as field trials , community based trials , place based trials , or ( as in this paper ) cluster r and omised trials . In an earlier discussion paper we considered the implication s of the CONSORT statement for the reporting of cluster r and omised trials . Here we present up date d guidance , based on the 2001 revision of the CONSORT statement This study reports the evaluation of an intervention design edto reinforcetobacco abstinence amongelementary schoolchildren in a school transition period . This intervention was developed according to the principles of Intervention Mapping . A total of 765 grade 5 students ( ages 10 - 12 ) was recruited in 32 elementary schools . A quasi-experimental longitudinal design was used to evaluate the outcomes . Results observed 2 and 8 months postintervention are reported here . It is shown that although the behavior remained largely unchanged by the intervention , some of its determinants were modified . Behavioral intention , behavioral and normative beliefs , perceived self-efficacy , and role beliefs were changed at one or both postintervention measures . An interesting feature of these results relates to the fact that the most positive outcomes were seen among at-risk children . Discussion considers the advisability to develop , implement , and evaluate evidence -based interventions targeting the psychosocial factors underlying maintenance of tobacco smoking abstinence in elementary school Most school-based smoking prevention studies employ design s in which schools or classrooms are assigned to different treatment conditions while observations are made on individual students . This design requires that the treatment effect be assessed against the between-school variance . However , the between-school variance is usually larger than the variance that would be obtained if students were individually r and omized to different conditions . Consequently , the power of the test for a treatment effect is reduced , and it becomes difficult to detect important treatment effects . To assess the potential loss of power or to calculate appropriate sample sizes , investigators need good estimates of the intraclass correlations for the variables of interest . The authors calculated intraclass correlations for some common outcome variables in a school-based smoking prevention study , using a three-level model-i.e . , students nested within classrooms and classrooms nested within schools . The authors present the intraclass correlation estimates for the entire data set , as well as separately by sex and ethnicity . They also illustrate the use of these estimates in the planning of future studies Bruno Giraudeau and Philippe Ravaud discuss the difficulties in preventing selection bias and applying intention-to-treat analysis in cluster r and omized trials , and propose some solutions BACKGROUND The 1985 Minnesota Legislature established guidelines for school-based tobacco-use prevention programming and provided financial incentives to school districts to encourage them to adopt a broad range of preventive measures . The Minnesota-Wisconsin Adolescent Tobacco-Use Research Project was funded by the National Cancer Institute in 1986 to evaluate the Minnesota initiative through two parallel studies . METHODS The Four Group Comparison Study was a prospect i ve study of 48 school " units " which were r and omly assigned to one of four conditions in 1987 . Baseline observations were taken in the sixth grade in 1987 , interventions were delivered in the seventh grade , and follow-up observations were taken in the seventh , eighth , and ninth grade s. The Four Group Comparison Study was design ed to evaluate the three middle-school interventions that were most widely adopted by Minnesota school districts as a result of the 1985 legislation . The Two State Comparison Study was a serial cross-sectional study of representative districts in Minnesota and Wisconsin . Annual surveys of ninth grade rs were conducted from 1986 - 1990 . The Two State Comparison Study was design ed to determine whether tobacco-use patterns changed in Minnesota relative to Wisconsin following the Minnesota legislation . RESULTS The prospect i ve study indicated that none of the interventions was more effective in reducing adolescent tobacco use compared with a r and omized control group . The serial cross-sectional study revealed that there was a modest net decline in Minnesota relative to Wisconsin from 1986 to 1990 , but that it was within the range of chance variation . CONCLUSIONS Taken together , these results indicate that this legislative initiative was insufficient to reduce adolescent tobacco use statewide during the 5-year study period . Together with results from other recent studies , they suggest that even more intensive efforts may be required to effect widespread reductions in adolescent tobacco use BACKGROUND Smoking is the leading preventable cause of premature death in the United States . Previous studies of financial incentives for smoking cessation in work setting s have not shown that such incentives have significant effects on cessation rates , but these studies have had limited power , and the incentives used may have been insufficient . METHODS We r and omly assigned 878 employees of a multinational company based in the United States to receive information about smoking-cessation programs ( 442 employees ) or to receive information about programs plus financial incentives ( 436 employees ) . The financial incentives were $ 100 for completion of a smoking-cessation program , $ 250 for cessation of smoking within 6 months after study enrollment , as confirmed by a biochemical test , and $ 400 for abstinence for an additional 6 months after the initial cessation , as confirmed by a biochemical test . Individual participants were stratified according to work site , heavy or nonheavy smoking , and income . The primary end point was smoking cessation 9 or 12 months after enrollment , depending on whether initial cessation was reported at 3 or 6 months . Secondary end points were smoking cessation within the first 6 months after enrollment and rates of participation in and completion of smoking-cessation programs . RESULTS The incentive group had significantly higher rates of smoking cessation than did the information-only group 9 or 12 months after enrollment ( 14.7 % vs. 5.0 % , P<0.001 ) and 15 or 18 months after enrollment ( 9.4 % vs. 3.6 % , P<0.001 ) . Incentive-group participants also had significantly higher rates of enrollment in a smoking-cessation program ( 15.4 % vs. 5.4 % , P<0.001 ) , completion of a smoking-cessation program ( 10.8 % vs. 2.5 % , P<0.001 ) , and smoking cessation within the first 6 months after enrollment ( 20.9 % vs. 11.8 % , P<0.001 ) . CONCLUSIONS In this study of employees of one large company , financial incentives for smoking cessation significantly increased the rates of smoking cessation . ( Clinical Trials.gov number , NCT00128375 . Objective : To assess the effect of an antismoking intervention focusing on adolescents in lower education . Students with lower education smoke more often and perceive more positive norms , and social pressure to smoke , than higher educated students . An intervention based on peer group pressure and social influence may therefore be useful to prevent smoking among these students . Design : Group r and omised controlled trial . Setting : 26 Dutch schools that provided junior secondary education . Subjects : 1444 students in the intervention and 1118 students in the control group , all in the first grade , average age 13 years . Intervention : Three lessons on knowledge , attitudes , and social influence , followed by a class agreement not to start or to stop smoking for five months and a class based competition . Main outcome measures : Comparison of smoking status before and immediately after and one year after the intervention , using multilevel analysis . Results : In the intervention group , 9.6 % of non-smokers started to smoke , in the control group 14.2 % . This leads to an odds ratio of 0.61 ( 95 % CI= 0.41 to 0.90 ) to uptake smoking in the intervention group compared with the control group . One year after the intervention , the effect was no longer significant . Conclusions : In the short-term , an intervention based on peer pressure decreases the proportion of adolescents with lower education who start smoking . Influencing social norms and peer pressure would therefore be a promising strategy in terms of preventing smoking among adolescents . The results also suggest that additional interventions in later years are needed to maintain the effect OBJECTIVES This study examined the effect of an orthodontist-delivered tobacco-use prevention program for adolescents . METHODS Southern California orthodontic offices were r and omly assigned to experimental ( n = 77 ) and control ( n = 77 ) groups . R and omly selected adolescents were interviewed at baseline and 2 years later ( n = 15,644 ) . Experimental offices received tobacco prevention training , anti-tobacco material s , and 50 cents for each anti-tobacco " prescription " written . RESULTS The 30-day tobacco use 2-year incidence rates for the control and experimental groups were 12.6 % and 12.0 % , respectively ; incidence rates for using tobacco more than 100 times were 7.6 % and 6.8 % . Differences between the groups did not reach significance . Mean prescription compliance was 64.4 % . A multivariate logistic model , showed a significant dose response : patients who received more prescriptions had lower incidence rates than those who received few or none ( 10 % vs 14 % ) . CONCLUSIONS Training , payment , and support did not ensure clinician compliance with prevention services . The dose effect suggests that replication under conditions that would ensure clinician compliance and statistical power would more thoroughly test clinicians ' ability to prevent tobacco use OBJECTIVES We assessed the effectiveness of a 2-year multicomponent , school-based intervention design ed to reduce tobacco use rates among adolescents in an urban area of India . METHODS Students from 32 schools in Delhi and Chennai , India , were recruited and r and omly assigned to an intervention or control group . Baseline , intermediate , and outcome data were collected from 2 cohorts of 6th- and 8th- grade students in 2004 ; 14,063 students took part in the study and completed a survey in 2004 , 2005 , or 2006 . The intervention consisted of behavioral classroom curricula , school posters , a parental involvement component , and peer-led activism . The main outcome measures were self-reported use of cigarettes , bidis ( small h and -rolled , often flavored , cigarettes ) , and chewing tobacco and future intentions to smoke or use chewing tobacco . RESULTS Findings showed that students in the intervention group were significantly less likely than were students in the control group to exhibit increases in cigarette smoking or bidi smoking over the 2-year study period . They were also less likely to intend to smoke or chew tobacco in the future . CONCLUSIONS School-based programs similar to the intervention examined here should be considered as part of a multi strategy approach to reducing tobacco use among young people in India BACKGROUND This paper examines the effectiveness of the " Smokefree Class Competition " with regard to primary and secondary prevention of smoking in adolescents . Each participating class has to decide if they want to be a " Smokefree Class " for the six-month period from fall to spring . Classes monitor their (non-)smoking behaviour and report it to the teacher regularly . Classes in which pupils refrain from smoking for this period of time participate in a prize draw , where they can win a number of attractive prizes . METHODS A control group study with repeated measurements was carried out in order to evaluate the effectiveness of the competition . The sample consisted of 131 participating and non-participating classes ( N of the pupils = 2,142 ; mean age 12.9 years , SD = 0.98 ) . Smoking status was assessed on two occasions : ( a ) prior to the beginning of the competition , and ( b ) 6 month after the end of the competition . RESULTS With regard to the smoking status at baseline no differences could be found between the experimental and the control group ( 15.2 % vs. 18.5 % smoking pupils ) . In the follow-up measurement , pupils in the control group showed significantly higher prevalences of smoking than the experimental group in the post-measurement period ( 32.9 % vs. 25.5 % smoking pupils ) . More pupils in the experimental group stayed smokefree compared to the control group . No differential effects on smoking cessation could be found . CONCLUSIONS The results show that participation in the competition could delay the onset of smoking in adolescents ( primary prevention ) . The competition is not effective in smoking cessation in youth OBJECTIVES Previous research has suggested that early smoking initiation predicts longer duration of smoking , heavier daily consumption , and increased chances of nicotine dependence . This report set out to estimate the relationship between smoking cessation and age of initiation , as well as nicotine dependence , sex , race , and education . METHODS A sample of 1007 young adults was r and omly selected from a large health maintenance organization in southeast Michigan . Hazard ratios of quitting associated with age at smoking initiation were estimated among 414 persons who smoked daily for 1 month or more . RESULTS With potential confounders controlled for , the likelihood of cessation was significantly higher in smokers who initiated smoking after age 13 . The hazard ratio for quitting associated with smoking initiation at ages 14 to 16 was 1.6 and with initiation at or after age 17 was 2.0 , compared with initiation at or before 13 years of age . Factors that decreased the likelihood of cessation were nicotine dependence and low education . CONCLUSIONS Public policy to discourage early smoking , if it succeeds in delaying the initiation of smoking , might contribute to the reduction of smoking-related mortality and morbidity by increasing the potential for quitting Background The Smokefree Class Competition , the largest school-based smoking prevention programme in Europe , aims to create a class climate that denormalises smoking . An analysis was carried out to assess whether it increases bullying or perception of isolation . Methods A cluster r and omised controlled trial was conducted , with two waves of assessment directly before the start and immediately after the end of the prevention programme . Some 3490 students were recruited from 84 secondary schools in Germany , of whom 3123 students ( 90 % ) provided data from both waves . Classes from the intervention group ( IG ) participated in the Smokefree Class Competition , committing themselves to stay smokefree for a period of 6 months , and self-monitoring their smoking status on a weekly basis . Classes that refrained from smoking were eligible for a prize draw . To test the hypotheses that participation in the competition might foster bullying , we measured students ' self report of ( 1 ) being victimised , ( 2 ) engaging in bullying and ( 3 ) being isolated . Results There was a strong association between daily smoking and higher odds of bullying others at baseline ( adjusted proportional OR 4.66 ; 95 % CI 3.38 to 6.43 ) . No significant pre – post differences across treatment assignment groups were found on any bullying measure using generalised linear latent and mixed models . For being isolated , the trends suggested that the programme , if anything , fostered lower levels of isolation at follow-up , especially for those who perceived high levels of isolation at baseline . Conclusion Participation in the intervention had no effect on bullying or perceptions of isolation . Trial Reg No IS RCT N27091233 in Current Control Trial Register This study examined the relative contribution of contingent payment and worksite CO monitoring to the long-term maintenance of smoking abstinence . Forty-seven hospital employees who had abstained from smoking for five days ( confirmed by CO analysis ) were r and omly assigned to one of three follow-up groups : ( a ) contingent payment/frequent monitoring ( n = 17 ) ; ( b ) noncontingent payment/frequent monitoring ( n = 16 ) ; or ( c ) non-contingent payment/infrequent monitoring ( n = 14 ) . Contingent payment combined with frequent CO monitoring delayed but did not ultimately prevent subjects relapse to smoking by the end of the six month follow-up . Contingent subjects maintained CO values less than or equal to 11 ppm significantly longer than did either the Non-contingent or the Control subjects ( p = .03 ) . CO monitoring alone had no effect on abstinence outcomes ; both Noncontingent and Control subjects showed high rates of early relapse Background The Smokefree Class Competition , a school-based smoking prevention intervention , is widely disseminated in Europe . Participating classes commit themselves to be smoke-free and self-monitor their smoking status . Classes that remain smoke-free for 6 months can win prizes . Effects of the intervention on current smoking , initiation and progression of smoking were investigated . Methods Cluster r and omised controlled trial . 84 schools ( 208 classes with 3490 students ; mean age 12.6 years , 50.4 % female ) in Saxony-Anhalt , Germany , were r and omly assigned to intervention or control condition . A baseline survey was conducted before the implementation of the programme , while post-test and follow-up surveys were carried out 7 ( immediately after the end of the competition ) , 12 and 19 months after baseline . Effects of participation in the programme on current and lifetime smoking were analysed by multilevel models controlling for confounding variables . Results Intervention students smoking occasionally at baseline smoked less frequently than students taking not part in the intervention at 7 and 12 months after baseline . Persistent beneficial programme effects were also found for lifetime smoking : intervention students were less likely to progress from experimental to established use . Conclusion Data suggest that Smokefree Class Competition reduces the probability of progressing from occasional and experimental stages of smoking to more established forms of use . Clinical trials registration number Trial registration IS RCT N27091233 in Current Control Trial Register OBJECTIVE To evaluate effects of a home-based antismoking socialization program on the initiation of smoking among children whose parents smoke . DESIGN Three-year r and omized controlled trial . PARTICIPANTS Parents who were current smokers and had a child in the third grade who had not tried smoking were eligible ; 873 parents-offspring pairs met these criteria , completed baseline interviews , and were r and omly assigned to the intervention or control condition ; 776 children ( 89 % ) completed an interview 3 years after baseline and were included in the study . INTERVENTION During 3 months , the intervention group ( n = 371 ) received 5 printed activity guides , parenting tip sheets , child newsletters , and incentives ; this group also received a booster activity guide 1 year later . The control group ( n = 405 ) received fact sheets about smoking . RESULTS Initiation of smoking ( first instance of puffing on a cigarette ) was reported by 12 % vs 19 % of children in the intervention vs control groups . Logistic regression analysis indicated that children in the control condition had twice the odds of reporting initiation of smoking as children in the intervention condition ( adjusted odds ratio , 2.16 ; P<.001 ) , after adjusting for child sex , parent sex , parent race , parent educational achievement , child 's best friends ' smoking , parent smoking rate at baseline , and parent cessation status . CONCLUSION Children in the pre-initiation phase of smoking who receive antismoking socialization from their parents are less likely to initiate smoking , even if their parents smoke The concept of “ forbidden fruit ” has been popularly associated with adolescent cigarette smoking in the US . However , only a few empirical studies have been conducted to investigate how this construct operates among adolescents . We examined the concurrent and prospect i ve relationships between two related concepts of forbidden fruit and adolescent cigarette smoking behavior and intention . We found some support for forbidden fruit attitudes as concurrent and longitudinal predictors of smoking and intention to smoke . Implication s of these findings are discussed PURPOSE The purpose of this article is to describe the diffusion and evaluation of the smoking prevention programme " Be Smart -- Don't Start " , the German " Smoke Free Class Competition " . METHOD The diffusion is described by means of numbers of participating classes and a representative population -based interview of 3,600 12 - 19-year-olds , which was conducted in 2005 . Two controlled and two r and omised controlled studies carried out in three countries ( Germany , Finl and and the Netherl and s ) with a total number of 12,812 adolescents ( N of the intervention group : 8,086 ; N of the control group : 4,726 ) have been realised to evaluate the intervention . RESULTS In 2005 20 % of all 12 - 15 year-olds and 9 % of all 16 - 19-year-olds living in Germany had participated in the programme . From baseline to follow-up test 12 - 24 months later smoking increased by 21.78 per cent points in the control group , compared to an increase of 16.02 per cent points in the intervention group . At follow-up 27.57 % of the pupils from the intervention group , and 35.91 % of the pupils from the control group are actual smokers ( odds ratio=0.65 , 95 % confidence interval : 0.57 - 0.74 ) . CONCLUSIONS Participating rate in the competition is high . The results indicate that the competition might have a short-term effect and be able to delay the onset of smoking CONTEXT Identifying effective obesity treatment is both a clinical challenge and a public health priority due to the health consequences of obesity . OBJECTIVE To determine whether common decision errors identified by behavioral economists such as prospect theory , loss aversion , and regret could be used to design an effective weight loss intervention . DESIGN , SETTING , AND PARTICIPANTS Fifty-seven healthy participants aged 30 - 70 years with a body mass index of 30 - 40 were r and omized to 3 weight loss plans : monthly weigh-ins , a lottery incentive program , or a deposit contract that allowed for participant matching , with a weight loss goal of 1 lb ( 0.45 kg ) a week for 16 weeks . Participants were recruited May-August 2007 at the Philadelphia VA Medical Center in Pennsylvania and were followed up through June 2008 . MAIN OUTCOME MEASURES Weight loss after 16 weeks . RESULTS The incentive groups lost significantly more weight than the control group ( mean , 3.9 lb ) . Compared with the control group , the lottery group lost a mean of 13.1 lb ( 95 % confidence interval [ CI ] of the difference in means , 1.95 - 16.40 ; P = .02 ) and the deposit contract group lost a mean of 14.0 lb ( 95 % CI of the difference in means , 3.69 - 16.43 ; P = .006 ) . About half of those in both incentive groups met the 16-lb target weight loss : 47.4 % ( 95 % CI , 24.5%-71.1 % ) in the deposit contract group and 52.6 % ( 95 % CI , 28.9%-75.6 % ) in the lottery group , whereas 10.5 % ( 95 % CI , 1.3%-33.1 % ; P = .01 ) in the control group met the 16-lb target . Although the net weight loss between enrollment in the study and at the end of 7 months was larger in the incentive groups ( 9.2 lb ; t = 1.21 ; 95 % CI , -3.20 to 12.66 ; P = .23 , in the lottery group and 6.2 lb ; t = 0.52 ; 95 % CI , -5.17 to 8.75 ; P = .61 in the deposit contract group ) than in the control group ( 4.4 lb ) , these differences were not statistically significant . However , incentive participants weighed significantly less at 7 months than at the study start ( P = .01 for the lottery group ; P = .03 for the deposit contract group ) whereas controls did not . CONCLUSIONS The use of economic incentives produced significant weight loss during the 16 weeks of intervention that was not fully sustained . The longer-term use of incentives should be evaluated . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00520611 |
788 | 25,043,647 | ENOS is a large completed international trial of blood pressure management in acute stroke and includes patients representative of many stroke services worldwide | BACKGROUND High blood pressure is common in acute stroke and associated with a worse functional outcome .
Many patients who present with acute stroke are taking prescribed antihypertensive therapy before their stroke .
AIMS ENOS tested whether lowering blood pressure and continuing pre-stroke antihypertensive therapy are each safe and effective . | Background and Purpose — Among patients with acute stroke , high blood pressure is often associated with poor outcome , although the reason is unclear . We analyzed data from the International Stroke Trial ( IST ) to explore the relationship between systolic blood pressure ( SBP ) , subsequent clinical events over the next 2 weeks , and functional outcome at 6 months in patients with acute stroke . Methods — We included in the analysis 17 398 patients from IST with confirmed ischemic stroke . A single measurement of SBP was made immediately before r and omization . Clinical events within 14 days of r and omization were recorded : recurrent ischemic stroke , symptomatic intracranial hemorrhage , death result ing from presumed cerebral edema , fatal coronary heart disease , and death . Survival and dependency were assessed at 6 months . Outcomes were adjusted for age , sex , clinical stroke syndrome , time to r and omization , consciousness level , atrial fibrillation , and treatment allocation ( aspirin , unfractionated heparin , both , or neither ) . Results — A U-shaped relationship was found between baseline SBP and both early death and late death or dependency : early death increased by 17.9 % for every 10 mm Hg below 150 mm Hg ( P < 0.0001 ) and by 3.8 % for every 10 mm Hg above 150 mm Hg ( P = 0.016 ) . The rate of recurrent ischemic stroke within 14 days increased by 4.2 % for every 10–mm Hg increase in SBP ( P = 0.023 ) ; this association was present in both fatal and nonfatal recurrence . Death result ing from presumed cerebral edema was independently associated with high SBP ( P = 0.004 ) . No relationship between symptomatic intracranial hemorrhage and SBP was seen . Low SBP was associated with a severe clinical stroke ( total anterior circulation syndrome ) and an excess of deaths from coronary heart disease ( P = 0.002 ) . Conclusions — Both high blood pressure and low blood pressure were independent prognostic factors for poor outcome , relationships that appear to be mediated in part by increased rates of early recurrence and death result ing from presumed cerebral edema in patients with high blood pressure and increased coronary heart disease events in those with low blood pressure . The occurrence of symptomatic intracranial hemorrhage within 14 days was independent of SBP Background and Purpose — The practicalities of doing ambulance-based trials where paramedics perform all aspects of a clinical trial involving patients with ultra-acute stroke have not been assessed . Methods — We performed a r and omized controlled trial with screening , consent , r and omization , and treatment performed by paramedics prior to hospitalization . Patients with probable ultra-acute stroke ( < 4 hours ) and systolic blood pressure ( SBP ) > 140 mm Hg were r and omized to transdermal glyceryl trinitrate ( GTN ; 5 mg/24 hours ) or none ( blinding under gauze dressing ) for 7 days with the first dose given by paramedics . The primary outcome was SBP at 2 hours . Results — Of a planned 80 patients , 41 ( 25 GTN , 16 no GTN ) were enrolled > 22 months with median age [ interquartile range ] 79 [ 16 ] years ; men 22 ( 54 % ) ; SBP 168 [ 46 ] ; final diagnosis : stroke 33 ( 80 % ) and transient ischemic attack 3 ( 7 % ) . Time to r and omization was 55 [ 75 ] minutes . After treatment with GTN versus no GTN , SBP at 2 hours was 153 [ 31 ] versus 174 [ 27 ] mm Hg , respectively , with difference −18 [ 30 ] mm Hg ( P=0.030 ) . GTN improved functional outcome with a shift in the modified Rankin Scale by 1 [ 3 ] point ( P=0.040 ) . The rates of death , 4 ( 16 % ) versus 6 ( 38 % ; P=0.15 ) , and serious adverse events , 14 ( 56 % ) versus 10 ( 63 % ; P=0.75 ) , did not differ between GTN and no GTN . Conclusions — Paramedics can successfully enroll patients with ultra-acute stroke into an ambulance-based trial . GTN reduces SBP at 2 hours and seems to be safe in ultra-acute stroke . A larger trial is needed to assess whether GTN improves functional outcome . Clinical Trial Registration — URL : http://www.controlled-trials.com/IS RCT N66434824/66434824 . Unique identifier : 66434824 High blood pressure ( BP ) , pulse pressure ( PP ) , and rate pressure product ( RPP ) are each associated independently with a poor outcome in acute ischemic stroke . Whereas nitric oxide ( NO ) donors , such as glyceryl trinitrate ( GTN ) , lower blood pressure in acute ischemic stroke , their effect on other hemodynamic measures is not known . We performed a systematic review of the effects of NO donors on systemic hemodynamic measures in patients with acute/subacute stroke . R and omized controlled trials were identified from search es of the Cochrane Library , Pubmed , and Embase . Information on hemodynamic measures , including systolic BP ( SBP ) , diastolic BP ( DBP ) , and heart rate , were assessed , and hemodynamic derivatives of these were calculated : PP ( PP = SBP - DBP ) , mean arterial pressure ( MAP = DBP + PP/3 ) , mid blood pressure ( MBP = ( SBP + DBP)/2 ) , pulse pressure index ( PPI = PP/MAP ) , and RPP ( RPP = SBP x HR ) . The effect of treatment on hemodynamic measures was calculated as the weighted mean difference ( WMD ) between treated and control groups with adjustment for baseline . Three trials involving 145 patients were identified ; 93 patients received the NO donor , GTN , and 52 patients composed the control group . Compared with placebo , GTN significantly reduced SBP ( WMD , -9.80 mm Hg ; P < .001 ) , DBP ( WMD , -4.43 mm Hg ; P < .001 ) , MAP ( WMD , - 6.41 mm Hg ; P < .001 ) , MBP ( WMD , -7.33 mm Hg ; P < .001 ) , PP ( WMD , -6.11 mm Hg ; P < .001 ) , and PPI ( WMD , -0.03 ; P = .04 ) . GTN increased HR ( WMD , + 3.87 bpm ; P < .001 ) and lowered RPP insignificantly ( WMD , -323 mm Hg.bpm ; P = .14 ) . Our findings indicate that the NO donor GTN reduces BP , PP , and other derivatives in acute and subacute stroke while increasing HR High blood pressure is common during the acute phase of stroke and is associated with a poor outcome . However , the management of high blood pressure remains unclear . The ‘ Efficacy of Nitric Oxide in Stroke ’ trial tested whether transdermal glyceryl trinitrate , a nitric oxide donor that lowers blood pressure , is safe and effective in improving outcome after acute stroke . Efficacy of Nitric Oxide in Stroke is an international multicenter , prospect i ve , r and omized , single-blind , blinded endpoint trial , with funding from the UK Medical Research Council . Patients with acute ischemic stroke or intracerebral hemorrhage and systolic blood pressure 140–220 mmHg were r and omized to glyceryl trinitrate or no glyceryl trinitrate and , where relevant , to continue or stop prestroke antihypertensive therapy . The primary outcome is shift in modified Rankin Scale at three-months . Patients or relatives gave written informed ( proxy ) consent , and all sites had research ethics approval . Analyses will be done by intention to treat . This paper and attachment describe the trial 's statistical analysis plan , developed prior to unblinding of date . The statistical analysis plan contains design and methods for analyses , and unpopulated tables and figures for the two primary publications and some secondary publications . The data base will be locked in late February 2014 in preparation for presentation of the results in May 2014 . The data from the trial will improve the precision of the estimates of the overall treatment effects ( efficacy and safety ) of results from completed trials of blood pressure management in acute stroke , and provide the first large-scale r and omized evidence on transdermal glyceryl trinitrate , and of continuing ( vs. stopping ) prestroke antihypertensive medications , in acute stroke High blood pressure in acute stroke is common and appears to be associated with a poor outcome . Lowering blood pressure might therefore improve outcome , provided that cerebral perfusion is not compromised . We assessed the effects of glyceryl trinitrate ( GTN ) on cerebral and systemic hemodynamic measures in acute stroke . Ninety patients with acute ischemic or hemorrhagic stroke were r and omized within 72 hours of ictus to transdermal GTN given daily for 10 days ( either 5 mg , 5 mg for 4 days then 10 mg , or 10 mg ) or control . Twenty-four hour blood pressure monitoring , middle cerebral artery blood velocity , cardiac output , augmentation index , and plasma nitric oxide levels were each measured at baseline and then on days 1 , 4 , 5 , and 10 . The primary outcome was blood pressure on day 1 . We found that GTN lowered mean peripheral arterial blood pressure on day 1 by 5.3 % to 6.7 % in a dose dependent manner as compared with control ( mean , SD ) : control , 108.8 ( 15.1 ) mmHg ; 5 mg , 102.5 ( 13.9 ) mmHg ; 5/10 mg , 103.4 ( 14.9 ) mmHg ; 10 mg , 101.5 ( 12.6 ) mmHg ; ( P = .005 ) . Increasing the dose from 5 to 10 mg on day 5 result ed in an overall reduction in blood pressure of 11.4 % as compared with leaving the dose at 5 mg ( P = .006 ) . GTN reduced peripheral pulse pressure , central aortic blood pressure , pulse pressure , and augmentation index on day 1 . Middle cerebral artery blood velocity and pulsatility index in the affected hemisphere , cardiac output , systemic peripheral resistance , and plasma nitric oxide levels were not altered by GTN . Treatment with GTN was associated with headache : control 0 ( 0 % ) , GTN 9 ( 15 % ) ( P = .027 ) ; no negative effect on end-of-treatment death or deterioration , or 3 month death or dependency was discernable . GTN reduced peripheral blood pressure in a dose-dependent fashion in patients with acute stroke at day 1 and also reduced central blood pressure and augmentation index . In contrast , GTN did not alter middle cerebral artery blood velocity or pulsatility index in the affected hemispheres , suggesting that cerebral blood flow did not change . A trial assessing the effect of lowering blood pressure with GTN on safety and functional outcome in patients with acute stroke is now warranted Background : Cellular phone conversations between on-scene patients or their legally authorized representatives ( LARs ) and off-scene enrolling physician-investigators require immediate and reliable connection systems to obtain explicit informed research consent in prehospital treatment trials . Methods : The NIH Field Administration of Stroke Therapy – Magnesium ( FAST-MAG ) Trial implemented a voice-over-internet protocol ( VOIP ) simultaneous ring system ( multiple investigator cell phones called simultaneously and first responder connected to call ) to enable physician-investigators to elicit consent immediately from competent patients or LARs encountered by 228 ambulances enrolling patients in a multicenter prehospital stroke trial . For 1 month , the number , origin , duration , and yield of enrolling line calls were monitored prospect ively . Results : Six investigators were connected to 106 enrolling line calls , with no identified unanswered calls . Thirty-five percent of new patient calls yielded an enrollment . The most common reasons for non-enrollment were last known well > 2 h ( n = 7 ) and uncon sentable patient without LAR available ( n = 7 ) . No non-enrollments were directly attributable to the VOIP system . In enrollments , consent was provided by the patient in 67 % and a LAR in 33 % . The duration of enrollment calls ( mean ± SD : 8.4 ± 2.5 min , range 6–14 ) was longer than non-enrollment calls ( 5.5 ± 3.5 , range 2–13 ; p < 0.001 ) . The median interval from last known well to study agent start was 46 min , and 70 % were enrolled within 60 min of onset . Conclusions : The simultaneous ring system was reliable and effective , permitting enrollment of a substantial number of patients within the first hour after stroke onset . VOIP cellular networks with simultaneous ring are a preferred means of facilitating consent in prehospital treatment trials High blood pressure ( BP ) is common in acute stroke and is independently associated with a poor outcome . Lowering BP might improve outcome if it did not adversely affect cerebral blood flow ( CBF ) or cerebral perfusion pressure . We investigated the effect of glyceryl trinitrate ( [ GTN ] an NO donor ) on quantitative CBF , BP , and cerebral perfusion pressure in patients with recent stroke . Eighteen patients with recent ( < 5 days ) ischemic ( n=16 ) or hemorrhagic ( n=2 ) stroke were r and omly assigned ( 2:1 ) to transdermal GTN ( 5 mg ) or control . CBF ( global , hemispheric , arterial territory , and lesion , using xenon computed tomography ) and BP ( peripheral and central ) were measured before and 1 hour after treatment with GTN . The effects of GTN on CBF and BP were adjusted for baseline measurements ( ANCOVA ) . GTN lowered peripheral systolic BP by ( mean ) 23 mm Hg ( 95 % CI , 2 to 45 ; P=0.03 ) and central systolic BP by 22 mm Hg ( 95 % CI , 0 to 44 ; P=0.048 ) . In contrast , GTN did not alter CBF ( mL/min per 100 g ) : global −1.2 ( 95 % CI , −6.5 to 4.2 ; P=0.66 ) and ipsilateral hemisphere −1.4 ( 95 % CI , −7.6 to 4.9 ; P=0.65 ) or area of stroke oligemia , penumbra , or core ( as defined by critical CBF limits ) . Contralateral CBF did not change : hemisphere 0 ( 95 % CI , −7 to 6 ; P=0.96 ) . GTN did not alter cerebral perfusion pressure or zero-filling pressure . Significant reductions in BP after transdermal GTN are not associated with changes in CBF or cerebral perfusion pressure or cerebral steal in patients with recent stroke . Trials need to assess the effect of lowering BP on functional outcome BACKGROUND Up to 50 % of patients with acute stroke are taking antihypertensive drugs on hospital admission . However , whether such treatment should be continued during the immediate post-stroke period is unclear . We therefore aim ed to assess the efficacy and safety of continuing or stopping pre-existing antihypertensive drugs in patients who had recently had a stroke . METHODS The Continue or Stop Post-Stroke Antihypertensives Collaborative Study ( COSSACS ) was a UK multicentre , prospect i ve , r and omised , open , blinded-endpoint trial . Patients were recruited at 49 UK National Institute for Health Research Stroke Research Network centres from January 1 , 2003 , to March 31 , 2009 . Patients aged over 18 years who were taking antihypertensive drugs were enrolled within 48 h of stroke and the last dose of antihypertensive drug . Patients were r and omly assigned ( 1:1 ) by secure internet central r and omisation to either continue or stop pre-existing antihypertensive drugs for 2 weeks . Patients and clinicians who r and omly assigned patients were unmasked to group allocation . Clinicians who assessed 2-week outcomes and 6-month outcomes were masked to group allocation . The primary endpoint was death or dependency at 2 weeks , with dependency defined as a modified Rankin scale score greater than 3 points . Analysis was by intention to treat . This trial is registered with the International St and ard R and omised Controlled Trial Register , number IS RCT N89712435 . FINDINGS 763 patients were assigned to continue ( n=379 ) or stop ( n=384 ) pre-existing antihypertensive drugs . 72 of 379 patients in the continue group and 82 of 384 patients in the stop group reached the primary endpoint ( relative risk 0.86 , 95 % CI 0.65 - 1.14 ; p=0.3 ) . The difference in systolic blood pressure at 2 weeks between the continue group and the stop group was 13 mm Hg ( 95 % CI 10 - 17 ) and the difference in diastolic blood pressure was 8 mm Hg ( 6 - 10 ; difference between groups p<0.0001 ) . No substantial differences were observed between groups in rates of serious adverse events , 6-month mortality , or major cardiovascular events . INTERPRETATION Continuation of antihypertensive drugs did not reduce 2-week death or dependency , cardiovascular event rate , or mortality at 6 months . Lower blood pressure levels in those who continued antihypertensive treatment after acute mild stroke were not associated with an increase in adverse events . These neutral results might be because COSSACS was underpowered owing to early termination of the trial , and support the continuation of ongoing research trials . FUNDING The Health Foundation and The Stroke Association INTRODUCTION The National Institutes of Health Stroke Scale ( NIHSS ) and Sc and inavian Stroke Scale ( SSS ) are both vali date d measures of neurologic impairment and have been used in many acute stroke trials . Methods for interconverting SSS and NIHSS are needed . METHODS Conversion equations were developed using linear regression ( both unadjusted , and adjusted for age and sex ) using a r and om 50 % of the data at both baseline and 90 days . The remaining 50 % of data were used to test the accuracy of the models produced . RESULTS Data from 5 acute stroke trials ( 2004 patients ) were included . Fitted models at baseline were NIHSS = 25.68 - 0.43 * SSS ( R(2 ) = 0.57 , prediction error [ PE ] -0.2 , P = .20 ) , and SSS = 50.37 - 1.63 * NIHSS ( R(2 ) = 0.59 , PE 0.2 , P = .35 ) . The 90-day models were NIHSS = 22.99 - 0.39 * SSS ( R(2 ) = 0.82 , PE -0.3 , P = .001 ) , and SSS = 56.68 - 2.20 * NIHSS ( R(2 ) = 0.80 , PE -0.4 , P = .08 ) . Adjustment did not material ly improve the R(2 ) values . CONCLUSION Total scores for NIHSS and SSS may be interconverted with good precision ; the mathematic conversion equations may prove useful in clinical practice and in comparison of data from observational studies and r and omized trials High blood pressure ( BP ) is common in acute stroke and is independently associated with a poor outcome . Many patients with acute stroke are taking antihypertensive medications . To test the safety and efficacy of 7 days of transdermal glyceryl trinitrate ( GTN , 5 mg/day ) vs. no GTN in patients with acute stroke ; patients taking antihypertensive therapy immediately before their stroke are also r and omised to continue vs. stop this temporarily . ENOS is a prospect i ve international multicentre single-blind r and omised-controlled trial in 5000 patients with acute ( < 48 h of onset ) ischaemic or haemorrhagic stroke . The primary outcome is combined death and dependency ( modified Rankin scale > 2 ) at 90 days measured by blinded central telephone follow-up . Secondary outcomes include : BP over the 7 days of treatment ; death , impairment ( Sc and inavian stroke scale ) , recurrence , and neuroimaging at 7 days ; discharge disposition , disability ( Barthel index ) , cognition ( mini-mental status examination ) and quality of life ( EuroQoL ) . The sample size will allow an absolute difference in death/dependency of 5 % to be detected with 90 % power at 5 % significance for GTN versus no GTN . R and omisation and data collection are performed over a secure Internet site with real-time data validation . Neuroimaging and serious adverse events are adjudicated blinded to treatment IMPORTANCE Although the benefit of reducing blood pressure for primary and secondary prevention of stroke has been established , the effect of antihypertensive treatment in patients with acute ischemic stroke is uncertain . OBJECTIVE To evaluate whether immediate blood pressure reduction in patients with acute ischemic stroke would reduce death and major disability at 14 days or hospital discharge . DESIGN , SETTING , AND PARTICIPANTS The China Antihypertensive Trial in Acute Ischemic Stroke , a single-blind , blinded end-points r and omized clinical trial , conducted among 4071 patients with nonthrombolysed ischemic stroke within 48 hours of onset and elevated systolic blood pressure . Patients were recruited from 26 hospitals across China between August 2009 and May 2013 . INTERVENTIONS Patients ( n = 2038 ) were r and omly assigned to receive antihypertensive treatment ( aim ed at lowering systolic blood pressure by 10 % to 25 % within the first 24 hours after r and omization , achieving blood pressure less than 140/90 mm Hg within 7 days , and maintaining this level during hospitalization ) or to discontinue all antihypertensive medications ( control ) during hospitalization ( n = 2033 ) . MAIN OUTCOMES AND MEASURES Primary outcome was a combination of death and major disability ( modified Rankin Scale score ≥3 ) at 14 days or hospital discharge . RESULTS Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg ( -12.7 % ) within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg ( -7.2 % ) in the control group within 24 hours after r and omization ( difference , -5.5 % [ 95 % CI , -4.9 to -6.1 % ] ; absolute difference , -9.1 mm Hg [ 95 % CI , -10.2 to -8.1 ] ; P < .001 ) . Mean systolic blood pressure was 137.3 mm Hg in the antihypertensive treatment group and 146.5 mm Hg in the control group at day 7 after r and omization ( difference , -9.3 mm Hg [ 95 % CI , -10.1 to -8.4 ] ; P < .001 ) . The primary outcome did not differ between treatment groups ( 683 events [ antihypertensive treatment ] vs 681 events [ control ] ; odds ratio , 1.00 [ 95 % CI , 0.88 to 1.14 ] ; P = .98 ) at 14 days or hospital discharge . The secondary composite outcome of death and major disability at 3-month posttreatment follow-up did not differ between treatment groups ( 500 events [ antihypertensive treatment ] vs 502 events [ control ] ; odds ratio , 0.99 [ 95 % CI , 0.86 to 1.15 ] ; P = .93 ) . CONCLUSION AND RELEVANCE Among patients with acute ischemic stroke , blood pressure reduction with antihypertensive medications , compared with the absence of hypertensive medication , did not reduce the likelihood of death and major disability at 14 days or hospital discharge . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01840072 Achieving balance on prognostic factors between treatment groups in a clinical trial is important to ensure that any observed treatment effect may be attributed to the treatment itself . Improving the balance on prognostic factors also potentially increases the statistical power attained in a trial . Substantial imbalances may occur by chance if simple r and omization is used . Allocation of the treatment according to stratified r and om blocks based on clinical features is the conventional approach to obtain treatment groups that are as similar as possible . An alternative approach , known as minimization ( or more generally as adaptive stratification ) , has also been proposed . We assessed the feasibility of adaptive stratification in the context of a clinical trial of insulin to control plasma glucose level following acute stroke . We determined suitable setting s for the parameters in the adaptive stratification procedure by simulation studies . Specifically , we assessed : the optimal probability for allocating a patient to the preferred ( leading to least imbalance on prognostic factors ) treatment group ; the number of variables that could be incorporated in the adaptive stratification algorithm ; the weighting that should be given to each variable ; and whether interactions between variables should be included . We then compared the statistical power , across a range of simulated treatment effects , between trials where treatments were allocated by stratified r and om blocks and by adaptive stratification . Finally , we considered the importance of the method of analysis in realizing the gain in power which may potentially be achieved by allocating treatments using stratified r and om blocks or adaptive stratification Background High blood pressure is a common complication in acute stroke and is associated with a poor outcome . Aims This study assesses the effects of transdermal glyceryl trinitrate on 24 h ambulatory blood pressure in patients with recent stroke . Methods One hundred and seven patients with acute ischaemic or haemorrhagic stroke were included . The patients had been enrolled in one of two trials of transdermal glyceryl trinitrate ( 5 mg daily ) or placebo/control , and underwent 24 h ambulatory blood pressure monitoring ( 56 glyceryl trinitrate , 51 control ) . Ambulatory blood pressure data were analysed using area under the curve for the entire 24 h , and day and night periods . Nocturnal dipping was defined as a decline in systolic blood pressure > 10 % . Comparisons of blood pressure between groups were performed by analysis of covariance ( ANCOVA ) with adjustments for trial and baseline measure . Results In comparison with control , glyceryl trinitrate significantly lowered 24 h blood pressure ( systolic blood pressure/ diastolic blood pressure 9·4/4·8 mmHg , P < 0·001/0·001 , n = 104 ) , daytime blood pressure ( 8·7/4·2 , P < 0·001/ < 0·001 , n = 103 ) and night-time blood pressure ( 6·9/1·7 , P = 0·008/0·458 , n = 86 ) . Only 86 patients ( glyceryl trinitrate 45 , placebo/control 41 ) had sufficient night blood pressure measurements to assign dipping status ; 28 were dippers ( 12 glyceryl trinitrate , 16 control ) and 58 were nondippers ( 33 glyceryl trinitrate , 25 control ) ; glyceryl trinitrate significantly lowered systolic but not diastolic blood pressure in both dippers and nondippers . Treatment with glyceryl trinitrate increased the daytime heart rate ( 4·8 beats/min ) but not the night-time heart rate . Patients whose blood pressure did not dip at night had a worse functional outcome at three-months . Conclusions Transdermal glyceryl trinitrate ( 5 mg ) significantly lowered 24 h blood pressure by 9/5 mmHg ( equivalent to a 6 % reduction ) in both dipping and nondipping patients with acute/subacute stroke . This reduction in blood pressure is clinical ly relevant and is unlikely to be excessive Background A poor outcome after stroke is associated independently with high blood pressure during the acute phase ; however , relationships with other haemodynamic measures [ heart rate ( HR ) , pulse pressure ( PP ) , rate – pressure product ( RPP ) ] remain less clear . Methods The Tinzaparin in Acute Ischaemic Stroke Trial is a r and omised , controlled trial assessing the safety and efficacy of tinzaparin versus aspirin in 1484 patients with acute ischaemic stroke . Systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) and HR measurements taken immediately prior to r and omization were averaged , and the mid-blood pressure ( MBP ) , PP , mean arterial pressure ( MAP ) , pulse pressure index , and RPP were calculated . The relationship between these haemodynamic measures and functional outcome ( death or dependency , modified Rankin Scale > 2 ) and early recurrent stroke , were studied with adjustment for baseline prognostic factors and treatment group . Odds ratios ( OR ) and 95 % confidence intervals ( CI ) refer to a change in haemodynamic measure by 10 points . Results A poor functional outcome was associated with SBP ( adjusted OR ; 1.11 ; 95 % CI , 1.03–1.21 ) , HR ( adjusted OR ; 1.15 ; 95 % CI , 1.00–1.31 ) , MBP ( adjusted OR ; 1.15 , 95 % CI , 1.03–1.29 ) , PP ( adjusted OR ; 1.14 ; 95 % CI , 1.02–1.26 ) , MAP ( adjusted OR ; 1.15 ; 95 % CI , 1.02–1.31 ) and RPP ( adjusted OR ; 1.01 ; 95 % CI , 1.00–1.02 ) . Early recurrent stroke was associated with SBP , DBP , MBP and MAP . Conclusions A poor outcome is independently associated with elevations in blood pressure , HR and their derived haemodynamic variables , including PP and the RPP . Agents that modify these measures may improve functional outcome after stroke BACKGROUND Magnesium is neuroprotective in animal models of stroke , and findings of small clinical pilot trials suggest potential benefit in people . We aim ed to test whether intravenous magnesium sulphate , given within 12 h of stroke onset , reduces death or disability at 90 days . METHODS 2589 patients were r and omised within 12h of acute stroke to receive 16 mmol MgSO4 intravenously over 15 min and then 65 mmol over 24 h , or matching placebo . Primary outcome was a global endpoint statistic expressed as the common odds ratio for death or disability at day 90 . Secondary outcomes were mortality and death or disability , variously defined as Barthel score less than 95 , Barthel score less than 60 , and modified Rankin scale more than 1 . Predefined subgroup analyses were for the primary endpoint in patients in whom treatment commenced within 6 h versus after 6 h , ischaemic versus non-ischaemic strokes , and cortical stroke syndromes versus non-cortical strokes . Intention-to-treat and efficacy analyses were done . FINDINGS The efficacy data set included 2386 patients . Primary outcome was not improved by magnesium ( odds ratio 0.95 , 95 % CI 0.80 - 1.13 , p=0.59 ) . Mortality was slightly higher in the magnesium-treated group than in the placebo group ( hazard ratio 1.18 , 95 % CI 0.97 - 1.42 , p=0.098 ) . Secondary outcomes did not show any treatment effect . Planned subgroup analyses showed benefit of magnesium in non-cortical strokes ( p=0.011 ) whereas greater benefit had been expected in the cortical group . INTERPRETATION Magnesium given within 12 h of acute stroke does not reduce the chances of death or disability significantly , although it may be of benefit in lacunar strokes Background and Purpose : Hypertension is a common medical complication in acute stroke and is associated with a poor outcome . However , no large trials have assessed the effect of lowering blood pressure ( BP ) on outcome , and it remains unclear how BP should be managed in acute stroke . We assessed , in a double-blind r and omised controlled trial , whether the nitric oxide ( NO ) donor glyceryl trinitrate ( GTN , a known systemic and cerebral vasodilator ) , would lower BP and alter platelet function . Methods : Thirty-seven patients with recent ( < 5 days ) ischaemic or haemorrhagic stroke were r and omised by minimisation to 12 days of daily treatment with transdermal GTN or matching placebo patches . Twenty-four-hour ambulatory BP was measured before and during GTN treatment at days 0 , 1 and 8 . Platelet aggregation and expression of adhesion molecules were assessed at the same time points . Functional outcome ( Rankin scale ) and case fatality were assessed at 3 months . Analysis was by intention-to-treat . Results : GTN significantly lowered BP by 13.0/5.2 mm Hg at day 1 and 9.3/5.0 mm Hg at day 8 . The lesser reduction at day 8 than day 1 suggests that tolerance to GTN was developing . Non-significant falls of 0.9/0.6 and 3.8/0.0 mm Hg occurred at days 1 and 8 , respectively , in the placebo group . GTN had no effect on heart rate , or platelet aggregation or expression of platelet adhesion molecules , including glycoproteins Ia , Ib , IIIa and P-selectin . Additionally , GTN did not alter case fatality or dependency , although the study was not powered for these outcomes . Conclusions : Transdermal GTN , an NO donor , lowered BP by 5–8 % , a clinical ly significant and relevant , but not excessive , degree in patients with acute stroke . However , GTN had no effect on platelet aggregation or expression of adhesion molecules . Since NO donors increase cerebral blood flow in patients with acute ischaemic stroke , GTN may be an appropriate drug for testing the effect of lowering BP on functional outcome Acute ischaemic stroke is characterised by reductions in local cerebral blood flow ( CBF ) and activation of circulating platelets and leucocytes . Nitric oxide is a vasodilator and can inhibit these circulating cells . The aim of this study was to assess the effect of nitric oxide on platelet function and regional CBF in patients with acute ischaemic stroke . Sodium nitroprusside ( SNP ) , a spontaneous nitric oxide donor , was administered at a dose which caused a 10 mm Hg fall in mean arterial blood pressure ( MABP ) in a pathophysiological study to 22 patients with acute ischaemic stroke and 12 matched control subjects . Platelet function ( whole blood aggregation and flow cytometry ) was assessed before and during SNP administration . Changes in regional CBF were measured using single photon emission computerised tomography ( SPECT ) scanning . SNP significantly reduced platelet aggregation in both the patient and control subject groups . Equally , the expression of platelet adhesion molecules P-selectin ( CD62 ) and glycoprotein ( GP ) GP IIIa ( CD61 ) were significantly reduced in both groups . GP Ia ( CDw49b ) expression was significantly attenuated in the patient but not in the control group . Four patients underwent SPECT scanning and improvements in local CBF corresponding to the penumbral area of the clinical stroke site were seen in 3 of these patients . A total of 24 regions of asymmetrical perfusion were examined , pre-SNP ( median ( SQR ) ) , 0.68 ( 0.14 ) vs. peri-SNP 0.78 ( 0.17 ) , 2p = 0.065 . SNP , given at a dose which reduced MABP by 10 mm Hg , significantly inhibited platelet aggregation and adhesion molecule expression . Improved regional CBF was seen in some patients . SNP is a c and i date therapeutic agent for patients with acute ischaemic stroke and warrants further study |
789 | 15,674,925 | Notably home based programs appeared to have a significantly higher adherence rate than center based programs .
AUTHORS ' CONCLUSIONS In the short-term , center based programs are superior to home based programs in patients with PVD .
There is a high possibility of a training effect however as the center based groups were trained primarily on treadmills ( and the home based were not ) and the outcome measures were treadmill based .
There is conflicting evidence which is better in patients with COPD .
Home based programs appear to be superior to center based programs in terms of the adherence to exercise ( especially in the long-term ) | BACKGROUND Physical inactivity is a leading cause of preventable death and morbidity in developed countries .
In addition physical activity can potentially be an effective treatment for various medical conditions ( e.g. cardiovascular disease , osteoarthritis ) .
Many types of physical activity programs exist ranging from simple home exercise programs to intense highly supervised hospital ( center ) based programs .
OBJECTIVES To assess the effectiveness of ' home based ' versus ' center based ' physical activity programs on the health of older adults . | Abstract Objective : To evaluate the effectiveness of combinations of three methods to promote physical activity . Design : R and omised controlled trial . Baseline assessment with post-intervention follow up at 12 weeks and 1 year . Setting : One urban general practice , 1995 - 7 . Participants : 523 adults aged 40 to 64 years , r and omised to four intervention groups and a control group . Interventions : Brief ( one interview ) or intensive ( six interviews over 12 weeks ) motivational interviewing based on the stages of change model of behaviour change , with or without financial incentive ( 30 vouchers entitling free access to leisure facilities ) . Main outcome measures : Physical activity score ; sessions of moderate and vigorous activity in the preceding four weeks . Results : Response rate was 81 % at 12 weeks and 85 % at one year . More participants in the intervention group reported increased physical activity scores at 12 weeks than controls ( 38 % v 16 % , difference 22 % , 95 % confidence interval for difference 13 % to 32 % ) , with a 55 % increase observed in those offered six interviews plus vouchers . Vigorous activity increased in 29 % of intervention participants and 11 % of controls ( difference 18 % , 10 % to 26 % ) , but differences between the intervention groups were not significant . Short term increases in activity were not sustained , regardless of intensity of intervention . Conclusions : The most effective intervention for promoting adoption of exercise was the most intensive . Even this did not promote long term adherence to exercise . Brief interventions promoting physical activity that are used by many schemes in the United Kingdom are of question able effectiveness . Key messages Schemes promoting physical activity are currently popular in general practice in Britain , but few have been rigorously evaluated and their effectiveness is unknown . In this study , the most effective intervention for promoting adoption of physical activity was the most intensive , involving six motivational interviews and a financial incentive A comparatively brief intervention ( one interview ) was only effective in the short term in around a third of participants Short term increases in physical activity were not maintained at one year follow up and even the most intensive intervention was ineffective in promoting long term adherence to increased physical activity . National and local government , health authorities , and primary healthcare teams should be cautious about current and future expenditure on , and implementation of , exercise prescription or referral Background and Purpose — A new gait training strategy for patients with stroke seeks to increase walking speed through treadmill training . This study compares the effects of structured speed-dependent treadmill training ( STT ) ( with the use of an interval paradigm to increase the treadmill speed stepwise according to principles of sport physiology ) with limited progressive treadmill training ( LTT ) and conventional gait training ( CGT ) on clinical outcome measures for patients with hemiparesis . Methods — Sixty ambulatory poststroke patients were each r and omly selected to receive 1 of the 3 different gait therapies : 20 subjects were treated with STT , 20 subjects were trained to walk on a treadmill with a 20 % increase of belt speed over the treatment period ( LTT ) , and 20 subjects were treated with CGT . Treatment outcomes were assessed on the basis of overground walking speed , cadence , stride length , and Functional Ambulation Category scores . Results — After a 4-week training period , the STT group scored significantly higher than the LTT and CGT groups for overground walking speed ( STT versus LTT , P < 0.001 ; STT versus CGT , P < 0.001 ) , cadence ( STT versus LTT , P = 0.007 ; STT versus CGT , P < 0.001 ) , stride length ( STT versus LTT , P < 0.001 ; STT versus CGT , P < 0.001 ) , and Functional Ambulation Category scores ( STT versus LTT , P = 0.007 ; STT versus CGT , P < 0.001 ) . Conclusions — Structured STT in poststroke patients result ed in better walking abilities than LTT or CGT . This gait training strategy provides a dynamic and integrative approach for the treatment of gait dysfunction after stroke Abstract The evaluation of a 13-month maintenance program ( MP ) for 39 severe COPD patients with FEV1%pred 44(7)% who , as result of two different 8-week leg exercise training ( LET ) programs , one supervised at the hospital ( group S ; n = 20 ) and the other self-monitored ( SM ; n = 19 ) , had achieved different levels of exercise tolerance . After LET , patients in group S had a higher maximal oxygen uptake and endurance time than patients in the SM group [ O2max 1.43(0.30 ) l · min−1 ] vs l.25(0.27 ) l · min−1 and endurance-time 16(4 ) min vs 12 ( 5 ) min , respectively ) . During the MP patients were advised to walk vigorously at least 4 km/day , 4 times/wk . After the MP , while endurance time remained higher than at baseline , it had decreased ( p < 0.01 ) immediately after LET in both groups and no differences were evident between groups ( 11(4 ) min and 10(4 ) , respectively ) . In contrast , Chronic Respiratory Diseases Question naire scores , which had improved significantly after LET in both groups , remained high . Long-term effects of MP were independent of the training strategy or whether physiological improvements had been obtained with the initial LET . SM exercise programs do not seem capable of maintaining physiological improvements in exercise tolerance , though “ quality of life ” can be maintained The purpose of this study was to determine the effect of intensity-controlled , grade d dance exercise and selected components of behavior modification on exercise adherence in overweight middle-aged women . Thirty-eight moderately overweight women , aged 35 to 58 , participated in a 16 1/2-week dance exercise program . Participants were r and omly assigned to an experimental group ( n = 20 ) that received intensity-controlled , grade d exercise and individual and group reinforcement , or to a control group ( n - 18 ) that exercised at a moderate intensity typical of commercial fitness classes and received no special reinforcement . Before exercise training began and at the completion of 16 1/2 weeks , a structured , open-ended interview was conducted . Ninety-four percent of the women in both groups adhered to the program , an exceptionally high adherence rate for this population . Eight participantidentified factors seemed to have influenced exercise adherence : group homogeneity , carpooling and social networks , pleasurable feelings associated with increased energy and fitness , leader with a health-related background , time limitation of exercise program , commitment to an established goal , desire to change body image , and desire to change health status and improve physical health BACKGROUND In patients with intermittent claudication , a supervised walking exercise program increases peak exercise performance and community-based functional status . Patients with peripheral arterial disease also have muscle weakness in the affected extremity that may contribute to the walking impairment . However , the potential benefits of training modalities other than walking exercise , such as strength training , have not been critically evaluated in this patient population . The present study tested the hypothesis that a strength training program would be as effective as treadmill walking exercise and that combinations of strengthening and walking exercise would be more effective than either alone in improving exercise performance . METHODS AND RESULTS Twenty-nine patients with disabling claudication were r and omized to 12 weeks of supervised walking exercise on a treadmill ( 3 h/wk at a work intensity sufficient to produce claudication ) , strength training ( 3 h/wk of resistive training of five muscle groups of each leg ) , or a nonexercising control group . Grade d treadmill testing was performed to maximally tolerated claudication pain to define changes in peak exercise performance . After 12 weeks , patients in the treadmill training program had a 74 + /- 58 % increase in peak walking time as well as improvements in peak oxygen consumption ( VO2 ) and the onset of claudication pain . Patients in the strength-trained group had a 36 + /- 48 % increase in peak walking time but no change in peak VO2 or claudication onset time . Control subjects had no changes in any of these measures over the 12-week period . After the first 12 weeks , patients in the initial walking exercise group continued for 12 more weeks of supervised treadmill training . This result ed in an additional 49 + /- 53 % increase in peak walking time ( total of 128 + /- 99 % increase over the 24 weeks ) . After the initial 12 weeks , patients in the strength-trained group began 12 weeks of supervised treadmill training , and patients in the control group participated in a 12-week combined program of strengthening and treadmill walking exercise . The combined strength and treadmill training program and treadmill training after 12 weeks of strength training result ed in increases in peak exercise performance similar to those observed with 12 weeks of treadmill training alone . CONCLUSIONS A supervised treadmill walking exercise program is an effective means to improve exercise performance in patients with intermittent claudication , with continued improvement over 24 weeks of training . In contrast , 12 weeks of strength training was less effective than 12 weeks of supervised treadmill walking exercise . Finally , strength training , whether sequential or concomitant , did not augment the response to a walking exercise program BACKGROUND Project ACTIVE was a r and omized clinical trial comparing two physical activity interventions , lifestyle and traditional structured exercise . The two interventions were evaluated and compared in terms of cost effectiveness and ability to enhance physical activity among sedentary adults . DESIGN This was a r and omized clinical trial . SETTING / PARTICIPANTS The study included 235 sedentary but healthy community-dwelling adults . INTERVENTION A center-based lifestyle intervention that consisted of behavioral skills training was compared to a structured exercise intervention that included supervised , center-based exercise . MAIN OUTCOME MEASURES The main outcome measures of interest included cost , cardiorespiratory fitness , and physical activity . RESULTS Both interventions were effective in increasing physical activity and fitness . At 6 months , the costs of the lifestyle and structured interventions were , respectively , $ 46.53 and $ 190.24 per participant per month . At 24 months these costs were $ 17.15 and $ 49.31 per participant per month . At both 6 months and 24 months , the lifestyle intervention was more cost-effective than the structured intervention for most outcomes measures . CONCLUSIONS A behaviorally-based lifestyle intervention approach in which participants are taught behavioral skills to increase their physical activity by integrating moderate-intensity physical activity into their daily lives is more cost-effective than a structured exercise program in improving physical activity and cardiorespiratory health . This study represents one of the first attempts to compare the efficiency of intervention alternatives for improving physical activity among healthy , sedentary adults STUDY OBJECTIVES To determine whether long-term treatment with exercise therapy results in more favorable , disease-specific , health-related quality of life ( HRQL ) compared with short-term treatment with exercise therapy ; and to determine whether there are gender differences in disease-specific HRQL among individuals r and omized into the two treatment groups . DESIGN R and omized clinical trial . SETTING Center-based exercise therapy unit at a university . PARTICIPANTS One hundred forty patients with COPD ; 118 completed trial . INTERVENTIONS Short-term exercise therapy ( 3 months ) ; long-term exercise therapy ( 18 months ) . MEASUREMENTS Chronic Disease Respiratory Question naire ( CRQ ) . RESULTS After 3 months of treatment , there were significant improvements in all CRQ scores for men and women ( p < 0.01 ) , and for the total sample ( p < 0.01 ) . At 18 months , individuals r and omized into the long-term group had significantly more favorable scores than the short-term group for dyspnea ( p = 0.03 ) , fatigue ( p < 0.01 ) , emotional function ( p = 0.04 ) , and mastery ( p = 0.04 ) . However , these effects were moderated by gender . That is , men in the long-term group reported significantly more favorable scores than men in the short-term group for dyspnea ( 0.04 ) , fatigue ( p < 0.001 ) , emotional function ( p = 0.02 ) , and mastery ( p = 0.02 ) . At the 18-month assessment , there were no differences between long-term and short-term exercise therapy for women on any of the subscales of the CRQ . CONCLUSIONS Taken collectively , the CRQ data demonstrate that long-term exercise therapy has little added benefit for women over short-term exercise therapy ; however , men derive significant benefits from extended training Objectives 1 . To assess the long-term effectiveness of a comprehensive cardiac rehabilitation programme on quality of life and survival in patients with a large spectrum of cardiovascular diseases ( myocardial infa rct ion , acute coronary syndrome , percutaneous transluminal coronary angioplasty and coronary artery bypass grafting ) . 2 . To establish the degree of correlation between expected improvement of health-related quality of life and improvement in physical function attributable to rehabilitation in the intervention group , in comparison with similar changes in the conventional care group . Design R and omized , controlled , parallel-group design ( intervention/conventional care ) . Setting Akershus County , southeast of Oslo City , Norway . Participants 500 patients , men and women , aged 40 - 85 years , who have sustained at least one of the above-mentioned cardiovascular diseases . Interventions 8 weeks of supervised , structured physical training of three periods of 20 min per week , targeting a heart rate of 60 - 70 % of the individual 's maximum ; home-based physical exercise training with the same basic schedule as in the supervised period ; quantification of patients ' compliance with the exercise programme by the use of wristwatches , information stored in the watch memory being retrieved once a month during the 3-year follow-up period ; and life-style modification with an emphasis on the cessation of smoking and on healthy nutrition and weight control BACKGROUND there have been few population -based , r and omized controlled trials on the effects of strength or endurance training on cardiovascular fitness in older women . OBJECTIVE to study the effects of strength or endurance training on cardiovascular fitness in women aged 76 - 78 years . DESIGN a population -based , r and omized controlled trial . SETTING exercise laboratory in a university faculty of sport and health sciences . SUBJECTS we r and omly assigned 42 medically-screened women aged 76 - 78 years , drawn from the population register to strength ( n=16 ) , endurance ( n=15 ) or control ( n=11 ) groups . METHODS subjects in the two exercise groups performed a supervised , individually tailored 18-week strength or endurance training programme . Controls continued with physical activity at their normal level . RESULTS the strength training group showed an increase in cycle ergometer peak power from 68.1 to 70.3 W ( P=0.035 compared with controls ) . Their peak power per kg body weight increased from 1.02 to 1.05 , while that of the endurance training group increased from 0.91 to 0.93 ( P=0.027 and P=0.049 respectively ) . Peak oxygen uptake increased from 18.1 to 19.7 ml x kg(-1 ) x min(-1 ) in the strength and from 17.1 to 18.2 in the endurance group ( non-significant ) . Six subjects ( 19 % ) in the exercise groups withdrew from the study because of health problems . CONCLUSIONS even with its limitations , the study suggests that the effect of 18-week strength or endurance training on cardiovascular fitness among women aged > /=75 is relatively small . Furthermore , health problems can emerge during training programmes in medically-screened elderly women BACKGROUND Physical activity programs in nursing homes typically consist of seated , range of motion ( ROM ) exercises , regardless of resident abilities . The Functional Fitness for Long-Term Care ( FFLTC ) Program was design ed not only to maintain ROM , but also to improve strength , balance , flexibility , mobility , and function . In addition , it was tailored to meet the needs of both high and low mobility residents . METHODS The feasibility and efficacy of the FFLTC Program were evaluated with 68 residents ( mean age 80 ) from five institutions . Persons were classified as low or high mobility and r and omized into either the FFLTC program or a seated ROM program . Classes were conducted in groups of 4 to 10 residents by trained facility staff for 45 minutes , three times per week . Assessment s at baseline and 4 months consisted of mobility , balance , gait , flexibility , functional capacity , and several upper and lower extremity strength measures . RESULTS Attendance averaged 86 % for the FFLTC and 79 % for the ROM classes . Four months of exercise led to significant improvements in mobility ( 16 % ) , balance ( 9 % ) , flexibility ( 36 % ) , knee ( 55 % ) , and hip ( 12 % ) strength for the FFLTC group . Shoulder strength was the only improvement found for the ROM group . The ROM group significantly deteriorated in some areas , particularly hip strength , mobility , and functional ability . CONCLUSIONS Institutionalized seniors , even those who are physically frail , incontinent and /or have mild dementia , can respond positively to a challenging exercise program . The FFLTC program demonstrated clear benefits over typical , seated ROM exercises . Moreover , with minimal training , the program can be safely delivered at low cost by institutional staff and volunteers AIM In this study , the effects of a 12-week hospital-based outpatient pulmonary rehabilitation program ( HRP ) are compared with those of a 12-week home-care rehabilitation program ( HCRP ) in COPD patients . A control group received no rehabilitation therapy . METHODS After r and omization and stratification , effects on lung function , exercise performance ( 4-min walking test and cycle ergometer test ) , dyspnea , and leg effort during exercise , and well-being were assessed in 45 COPD patients with moderate to severe airflow limitation ( mean [ SD ] FEV1 percent predicted , 42.8 [ 8.4 ] ) . RESULTS After HRP and HCRP , at 3 to 6 months after the start of the study , equal improvements were detected in exercise capacity and in Borg dyspnea and leg effort scores at similar work levels during the cycle test . However , whereas after HRP at longer term values tended to return to baseline outcome , after HCRP a further ongoing significant improvement in exercise capacity was observed , while Borg dyspnea scores remained significantly improved over 18 months . Improvements in cycle workload and dyspnea score were significantly better maintained after HCRP as compared with HRP . Lung function , arterial oxygen saturation , and heart frequency during exercise did not change . A significant improvement in well-being was maintained over 18 months in both rehabilitation groups . CONCLUSION Beneficial effects are achieved both after a HRP and a HCRP in COPD patients with moderate to severe airflow limitation . Yet we recommend to initiate HCRPs as improvements are maintained longer and are even further strengthened in this setting OBJECTIVES To examine the effects of 18-month aerobic walking and strength training programs on static postural stability among older adults with knee osteoarthritis . DESIGN R and omized , single-blind , clinical trial of therapeutic exercise . SETTING Both center-based ( university ) and home-based . PARTICIPANTS A cohort of 103 older adults ( age = 60 years ) with knee osteoarthritis who were participants in a large ( n = 439 ) clinical trial and who were r and omly assigned to undergo biomechanical testing . INTERVENTION An 18-month center- ( 3 months ) and home-based ( 15 months ) therapeutic exercise program . The subjects were r and omized to one of three treatment arms : ( 1 ) aerobic walking ; ( 2 ) health education control ; or ( 3 ) weight training . MEASUREMENTS Force platform static balance measures of average length ( Rm ) of the center of pressure ( COP ) , average velocity ( Vel ) of the COP , elliptical area ( Ae ) of the COP , and balance time ( T ) . Measures were made under four conditions : eyes open , double- and single-leg stances and eyes closed , double- and single-leg stances . RESULTS In the eyes closed , double-leg stance condition , both the aerobic and weight training groups demonstrated significantly better sway measures relative to the health education group . The aerobic group also demonstrated better balance in the eyes open , single-leg stance condition . CONCLUSIONS Our results suggest that long-term weight training and aerobic walking programs significantly improve postural sway in older , osteoarthritic adults , thereby decreasing the likelihood of larger postural sway disturbances relative to a control group Supervised , hospital-based exercise rehabilitation programs are effective for improving functional status for patients with claudication due to peripheral arterial occlusive disease . However , it has been suggested that unsupervised , home-based exercise programs , which have been relatively little evaluated , would be equally efficacious as compared with hospital-based programs . The authors tested the hypothesis that a hospital-based exercise rehabilitation program would improve treadmill exercise perfor mance more than a home-based program . Of 20 consecutively enrolled patients with claudication , 10 were r and omly placed into a supervised , hospital-based program and 10 into an unsupervised , home-based program for a three-month period . Exercise perfor mance was evaluated by treadmill testing using a grade d protocol . In addition , func tional status was evaluated by the Walking Impairment Question naire ( WIQ ) and the Medical Outcomes Study SF-20 question naire ( MOS ) . Patients in the hospital-based program were treated with treadmill walking three times a week for one hour/visit . Patients in the home-based program were instructed to walk at least three times a week and were contacted weekly to provide encouragement and to record compliance with ( continued on next page ) the program . Patients in the hospital-based group improved peak walking time by 137 % , pain-free walking time by 150 % , and peak oxygen consumption by 19 % ( all P<0.05 ) . Patients reported an improved walking distance and speed according to WIQ data ( both P<0.05 ) . In addition , the MOS physical functioning score in the hospital-based group improved by 20 percentage points ( P<0.05 ) . In contrast , patients in the home-based program did not improve exercise performance measured on the treadmill . Improvement in the ability to walk on the treadmill was greater in the hospital-based than the home- based program ( P<0.05 ) . The ability to walk distances was the only question naire measure that improved in persons who received the home-based program ( P<0.05 ) . Preliminary results suggest that a supervised , hospital-based program is more effective for improving treadmill exercise performance than an unsupervised , home-based program Positional feedback ( PF ) and electrical stimulation were combined in a new treatment modality for facilitating wrist extension in stroke patients . Thirty adult hemiparetic patients lacking normal voluntary wrist extension were r and omly placed in control and study groups . The control group received conventional therapy while the study group received positional feedback stimulation training ( PFST ) in addition to conventional treatment . At the end of the 4-week program , study patients showed a 280 % increase in isometric extension torque when the wrist was positioned in 30 degrees of extension and 70 % increase when positioned in 30 degrees of flexion . Control patients showed no significant changes in torque . Study patients made an average 200 % gain in selective range of motion over their starting levels while controls made only a 50 % increase . Treatment using automated PFST equipment allows controlled repetitive isotonic exercise and facilitation of wrist extension without continuous one-on-one therapist/patient supervision OBJECTIVE Because blood lactic acid ( LA ) levels may be important in prescribing exercise for cardiac patients , this study documented the LA response to four different circuit weight training ( CWT ) protocol s and compared these responses to both maximal treadmill and LA threshold values . DESIGN Intervention study following a crossover trial design . SETTING A phase III community-based setting . PATIENTS All subjects had documented cardiac disease and were volunteers . INTERVENTIONS We used 40 % and 60 % of the one-repetition maximum ( 1-RM ) for six exercises and 30 or 60sec of rest between each station , result ing in four protocol s , performed in r and om order . A discontinuous treadmill test was conducted , and the LA threshold was determined . MAIN OUTCOME MEASURE The main dependent variable was LA after each CWT protocol . RESULTS No signs or symptoms suggestive of cardiovascular distress during any of the four CWT protocol s were reported . A repeated- measures analysis of variance showed that the LA threshold value was significantly less than all four CWT protocol s ( p < .05 ) . The CWT responses were also compared with the traditional LA threshold value of 4.0mmol/L , and both 60 % protocol s were significantly elevated ( p < .05 ) . CONCLUSION Because no positive signs or symptoms were reported , we recommend starting stable cardiac patients on a CWT program with an initial load between 40 % and 60 % 1-RM and allowing at least 60sec of rest between exercises In this study the effects of rehabilitation teaching plus exercise testing on perceived self-efficacy for and performance of daily activities were compared with and without exercise training . Subjects were patients who had had myocardial infa rct ion or cardiac surgery ( mean age 57.7 + /- 11.3 years ) and who had already received inpatient rehabilitation services . Subjects were r and omly assigned to one of three groups . Treatment group 1 ( n = 11 ) received teaching , treadmill exercise testing , and exercise training ( three times weekly for 5 weeks ) . Treatment group 2 ( n = 15 ) received only teaching and exercise testing . The control group ( n = 14 ) received only routine care without supervised exercise or teaching . Measurements of self-efficacy and activity performance were made at hospital discharge and at 4 and 9 weeks after the cardiac event . Repeated- measures analysis of variance showed an increase in self-efficacy scores ( p less than 0.001 ) and performance of physical activity ( p less than 0.001 ) for all groups . Both treatment groups , especially the training group , obtained the highest scores , but differences between groups were nonsignificant ( p greater than 0.05 ) . These results indicate that in a sample of uncomplicated , motivated patients who had participated in a phase 1 inpatient rehabilitation program , substantial improvements in self-efficacy and performance of daily activities were made early in recovery , before the onset of phase 2 , formalized outpatient therapy PURPOSE The effects of upper-limb ( arm cranking ) and lower-limb ( leg cranking ) exercise training on walking distances in patients with intermittent claudication was assessed . METHODS Sixty-seven patients ( 33 to 82 years old ) with moderate to severe intermittent claudication were recruited , and the maximum power generated during incremental upper- and lower-limb ergometry tests was determined , as were pain-free and maximum walking distances ( by using a shuttle walk test ) . Patients were r and omly assigned to an upper-limb training group ( n = 26 ) or a lower-limb training group ( n = 26 ) . An additional untrained group ( n = 15 ) was recruited on an ad hoc basis in parallel with the main trial by using identical inclusion criteria . This group was subsequently shown to possess a similar demographic distribution to the two exercise groups . Supervised training sessions were held twice weekly for 6 weeks . RESULTS Both training programs significantly improved the maximum power generated during the incremental upper- and lower-limb ergometry tests ( P < . 001 ) , which may reflect an increase in central cardiovascular function that was independent of the training mode . More importantly , pain-free and maximum walking distances also improved in both training groups ( P < .001 ) . The improvements in the training groups were similar ; there were no changes in the untrained control group . These findings suggest that the symptomatic improvement after upper-limb exercise training may result , in part , from systemic cardiovascular effects rather than localized metabolic or hemodynamic changes . CONCLUSION Carefully prescribed upper-limb exercise training can evoke a rapid symptomatic improvement in patients with claudication , while avoiding the physical discomfort experienced when performing lower-limb weight-bearing exercise Study objective : To compare health walks , a community based lay-led walking scheme versus advice only on physical activity and cardiovascular health status in middle aged adults . Design : R and omised controlled trial with one year follow up . Physical activity was measured by question naire . Other measures included attitudes to exercise , body mass index , cholesterol , aerobic capacity , and blood pressure . Setting : Primary care and community . Participants : 260 men and women aged 40–70 years , taking less than 120 minutes of moderate intensity activity per week . Main results : Seventy three per cent of people completed the trial . Of these , the proportion increasing their activity above 120 minutes of moderate intensity activity per week was 22.6 % in the advice only and 35.7 % in the health walks group at 12 months ( between group difference = 13 % ( 95 % CI 0.003 % to 25.9 % ) p=0.05 ) . Intention to treat analysis , using the last known value for missing cases , demonstrated smaller differences between the groups ( between group difference = 6 % ( 95 % CI −5 % to 16.4 % ) ) with the trend in favour of health walks . There were improvements in the total time spent and number of occasions of moderate intensity activity , and aerobic capacity , but no statistically significant differences between the groups . Other cardiovascular risk factors remained unchanged . Conclusions : There were no significant between group differences in self reported physical activity at 12 month follow up when the analysis was by intention to treat . In people who completed the trial , health walks was more effective than giving advice only in increasing moderate intensity activity above 120 minutes per week The effects of two 8-week programmes of exercise reconditioning on the time constants ( tau ) of the pulmonary gas exchange , ventilatory and heart rate responses to moderate intensity exercise in patients with chronic obstructive pulmonary disease ( COPD ) were studied . Thirty-five subjects ( mean+/-SD 64+/-5 yrs ; forced expiratory volume in one second ( FEV1 ) 1.09+/-0.17 L ; 41+/-6.2 % predicted ) were r and omly assigned either to supervised ( s ) training on a treadmill , 4 days x week(-1 ) ( group S ; n=21 ) or self-monitored ( SM ) walking 3 or 4 km in 1 h 4 days x week(-l ) ( group SM ; n=20 ) . The different levels of supervision result ed in a different estimated intensity of training ( 35+/-10 W in the SM group and 70+/-22 W in the S group ) . The kinetics were evaluated with a constant-load exercise test on a cycle-ergometer at a work rate corresponding to 80 % the highest oxygen consumption ( V'O2 ) that can be achieved without blood lactic acidosis ( V'O2,LAT ) or 50 % of V'O2,max , if maximum oxygen consumption V'O2,LAT was not found . Mean endurance time at a work rate equivalent to 70 % of the pretraining V'O2,max increased by 493+/-281 s in the S group and 254+/-283 s in the SM group ( p<0.001 ) . Mean tauV'O2 decreased from 83+/-17 s to 67+/-11 s ( p<0.0001 ) in the S group and from 84+/-12 to 79+/-16 ( p=0.04 ) in the SM group . Mean tau for carbon dioxide output minute ventilation and heart rate were also speeded after training , again more markedly in the S group . In the S group there was a significant correlation between the decrease in tauV'O2 and the increase in endurance time ( r=-0.56 , SEM=0.21 ) . It is concluded that training speeds the kinetic response of oxygen consumption , carbon dioxide production , minute ventilation and heart rate to moderate exercise and that the effect is greater after supervised , more intense training OBJECTIVE To test the hypothesis that training-related improvements in glucose and insulin responses to an oral glucose tolerance test ( OGTT ) are independent of changes in abdominal adiposity . DESIGN Adiposity and responses to an OGTT were measured before and after a 4-month r and omized , controlled aerobic training program . SETTING An academic medical institution . PARTICIPANTS Sixteen healthy older ( 73+/-1 year ) men and women . INTERVENTION Both the training ( T ) ( n=9 ) and control ( C ) ( n=7 ) groups exercised 4 times a week for 60-minute sessions . T exercised on mini-trampolines at 55 to 65 % of HRmax ( determined from a grade d treadmill test ) for 1 month and then at 75 % for 3 months ; C engaged in supervised stretching and yoga . MEASUREMENTS At baseline and follow-up , we estimated abdominal fat ( from computed tomography and anthropometry ) , plasma glucose , and serum insulin responses to the OGTT and fasting concentrations of free fatty acids ( FFA ) . RESULTS Aerobic training result ed in a 16 % increase in VO2 peak and a 24 % decrease in FFA in the T group ( P < .05 ) , but training had no effect on abdominal fat . In the T group , the glucose response curve shifted to the left , and the incremental area under the glucose curve decreased by 25 % ( P < .05 ) . This improvement in glucose response occurred , however , only in those with impaired glucose tolerance at baseline and without any observed change in insulin response . No change in any variables occurred in the C group . CONCLUSIONS Our data suggest that moderate-intensity aerobic training has a favorable effect on glucose tolerance in older people , independent of changes in abdominal adiposity BACKGROUND Orientation sessions are sometimes used to habituate subjects before exercise stress testing . The extent of habituation in older subjects has not been clearly defined . Additionally , the use of repetitive maximal stress testing as an orientation method may not be necessarily applicable in the aged . METHODS To determine if the employment of a submaximal orientation session would effect cardiopulmonary cycle ergometer exercise results , 266 older adults ( 68.6 + /- 5.0 years ) male ( n = 100 ) and female ( n = 166 ) subjects participated in this study . One hundred thirty-one subjects received an orientation before stress testing . One hundred thirty-five did not . RESULTS Analysis of resting values revealed no significant differences . Separate gender analysis was performed at submaximal workloads . Men were examined at 0 , 60 , and 105 Watts ; women at 0 , 45 , and 75 Watts . Oriented subjects displayed significantly lower heart rates for both males and females at all submaximal workloads . Oxygen uptake was significantly lower for oriented women at 45 Watts ( P < or = .05 ) and men at 60 Watts ( P < or = .05 ) . Oriented males displayed significantly lower systolic blood pressure at 0 Watts ( P < or = .05 ) , 60 Watts ( P < or = .01 ) , and 105 Watts ( P < or = .05 ) . The oriented group reached ventilatory threshold ( VeT ) at a higher workload ( P < or = .001 ) , lower heart rate ( P < or = .001 ) , and higher VO2 uptake ( P < or = .05 ) . Nonoriented subjects obtained a significantly higher maximal heart rate than oriented subjects ( 147 + /- 15.7 beats per minute ( bpm ) vs. 140 + /- 17.1 bpm , P < or = .01 ) . Separate gender analysis revealed a significant difference ( P < or = .01 ) in maximal heart rate in males ( oriented = 137.4 + /- 18.8 bpm vs. nonoriented = 147.7 + /- 15.7 bpm ) . Although nonoriented women achieved a higher maximal heart rate , the difference was not significant ( 146.9 + /- 15.8 bpm vs. 142.6 + /- 16.0 bpm ) . CONCLUSION These results indicate that both male and female older subjects display significant modification in physiologic performance from habituation after a single submaximal exercise orientation session . This effect was greater at submaximal than maximal workloads , and appears to be greater than that previously reported in younger subjects BACKGROUND Most patients with coronary heart disease are overweight . However , only minimal weight loss occurs with participation in a st and ard cardiac rehabilitation ( CR ) program . METHODS The study investigated 82 patients with coronary heart disease who entered an outpatient CR program and completed 36 sessions of exercise over a 12-week period . The effects of a structured , nurse-coordinated , weight loss intervention during phase 2 CR were compared with those observed in a CR control group receiving usual care . RESULTS The intervention group lost an average of 4.3 + /- 2.8 kg ( P < .0001 ) , as compared with a weight loss of 1.7 + /- 2.6 kg ( P < .001 ) in the control group ( P < .005 between groups ) . The effect of the weight loss intervention on total cholesterol ( 172 + /- 34 to 166 + /- 29 mg/dL ) differed from the response in a control group receiving usual care ( 180 + /- 30 to 187 + /- 28 mg/dL ) ( P < .05 between groups ) . The weight loss group experienced a significantly greater improvement ( P < .05 ) than the control group in the physical function score on the Medical Outcomes Study SF-36 question naire . A significant correlation was found between the number of weight loss sessions an individual attended and the amount of weight loss experienced ( R = 0.39 ; P < .05 ) . CONCLUSIONS The current study demonstrated that a behavioral weight loss intervention is effective in reducing body weight in a CR setting . Participants in the intervention group experienced significantly greater improvements in body weight , body mass index , and total cholesterol than a control group . Additionally , participants in the weight loss program reported greater improvements in their physical function score than the control patients STUDY OBJECTIVES To compare the effectiveness of two forms of exercise training in pulmonary rehabilitation . DESIGN A prospect i ve , r and omized , unblinded , 8-week trial . SETTING A hospital-based outpatient pulmonary rehabilitation program . PATIENTS Forty patients ( 20 patients in each group ) with COPD who were referred for pulmonary rehabilitation . INTERVENTIONS We compared the short-term effectiveness of a high-intensity , lower-extremity endurance program with a low-intensity , multicomponent calisthenics program for the rehabilitation of patients with COPD . The high-intensity group trained predominately on the stationary bicycle and treadmill , with a goal of exercising at > or = 80 % of maximal level determined from incremental testing for 30 min per session . The low-intensity group performed predominately classroom exercises for approximately 30 min per session . For both groups , twice-weekly sessions were held for 8 weeks . The primary outcome measure was health status , measured using the Chronic Respiratory Disease Question naire . Other outcomes included peak oxygen consumption on incremental treadmill exercise testing , exertional dyspnea , treadmill endurance time , the number of sit-to-st and repetitions and arm lifts in 1 min , overall dyspnea , and question naire-rated functional status . MEASUREMENTS AND RESULTS Both groups showed significant postrehabilitation improvement in exercise variables , exertional and overall dyspnea , functional performance , and health status . Patients in the high-intensity group showed greater increases in treadmill endurance and greater reductions in exertional dyspnea , whereas those in the low-intensity group showed greater increases in arm-endurance testing . Both groups had similar improvements in overall dyspnea , functional performance , and health status . CONCLUSIONS Despite differences in exercise performance , both high-intensity , lower-extremity endurance training and low-intensity calisthenics led to similar short-term improvements in question naire-rated dyspnea , functional performance , and health status BACKGROUND AND PURPOSE Many patients have impaired arm function after stroke , for which they receive physiotherapy . The aim of the study was to determine whether increasing the amount of physiotherapy early after stroke improved the recovery of arm function and to compare the effects of this therapy when administered by a qualified therapist or a trained , supervised assistant . The physiotherapy followed a typical British approach , which is Bobath derived . Ten hours of additional therapy were given over a 5-week period . METHODS The study design was a single-blind , r and omized , controlled trial . Stroke patients were recruited from those admitted to the hospital in the 5 weeks after stroke . They were r and omly allocated to routine physiotherapy , additional treatment by a qualified physiotherapist , or additional treatment by a physiotherapy assistant . Outcome was assessed after 5 weeks of treatment and at 3 and 6 months after stroke on measures of arm function and of independence in activities of daily living . RESULTS There were 282 patients recruited to the study . The median initial Barthel score was 6.5 , and the median age of the patients was 73 years . The median initial Rivermead Motor Assessment Arm score was 1 . There were no significant differences between the groups at r and omization or on any of the outcome measures . Only half of the patients allocated to the 2 additional-therapy groups completed the program . CONCLUSIONS This increase in the amount of physiotherapy for arm impairment with a typical British approach given early after stroke did not significantly improve the recovery of arm function in the patients studied . A number of other studies of interventions aim ed at rehabilitation of arm function have reported positive results . Such findings may have been due to the content of these interventions , to the greater intensity of the interventions , or to the selection of patients to whom the treatments were applied Abstract Objectives : To determine whether a home based exercise programme can improve outcomes in patients with knee pain . Design : Pragmatic , factorial r and omised controlled trial of two years ' duration . Setting : Two general practice s in Nottingham . Participants : 786 men and women aged—45 years with self reported knee pain . Interventions : Participants were r and omised to four groups to receive exercise therapy , monthly telephone contact , exercise therapy plus telephone contact , or no intervention . Patients in the no intervention and combined exercise and telephone groups were r and omised to receive or not receive a placebo health food tablet . Main outcome measures : Primary outcome was self reported score for knee pain on the Western Ontario and McMaster universities ( WOMAC ) osteoarthritis index at two years . Secondary outcomes included knee specific physical function and stiffness ( scored on WOMAC index ) , general physical function ( scored on SF-36 question naire ) , psychological outlook ( scored on hospital anxiety and depression scale ) , and isometric muscle strength . Results : 600 ( 76.3 % ) participants completed the study . At 24 months , highly significant reductions in knee pain were apparent for the pooled exercise groups compared with the non-exercise groups ( mean difference -0.82 , 95 % confidence interval -1.3 to -0.3 ) . Similar improvements were observed at 6 , 12 , and 18 months . Regular telephone contact alone did not reduce pain . The reduction in pain was greater the closer patients adhered to the exercise plan . Conclusions : A simple home based exercise programme can significantly reduce knee pain . The lack of improvement in patients who received only telephone contact suggests that improvements are not just due to psychosocial effects because of contact with the therapist OBJECTIVE The objective of the present study was to determine whether appropriate endurance exercise training improves cardiac function in patients with prior myocardial infa rct ion . METHODS Twenty-nine patients with prior myocardial infa rct ion were divided into three groups ( Group 1 : control , Group 2 : low-intensity training , Group 3 : high-intensity training ) . Low and high training intensities were determined according to the gas exchange threshold of each patient . The patients in Groups 2 and 3 performed 15 min of home-based physical training safely , twice a day , 5 days a week for 2 months . Prior to and following this training , each patient performed two constant work rate tests ( moderate and heavy intensity ) and a symptom-limited incremental exercise test . RESULTS Heart rates at rest and during exercise were decreased significantly after 2 months in all three groups . Stroke volume at rest increased significantly after 2 months only in Group 3 . Stroke volume after 6 min of heavy-intensity exercise increased significantly in Groups 2 and 3 . However , the ejection fraction at 6 min of heavy-intensity exercise increased significantly only in Group 3 . The maximal work rate attained during incremental exercise testing increased significantly in Groups 2 and 3 . This parameter did not significantly change in the control group . CONCLUSIONS Effects of physical training on maximal exercise capacity were noted in both exercise training groups . However , improvement in cardiac function ( such as stroke volume ) , both at rest and during exercise , was noted only in the high-intensity training group . Our results suggest that relatively high-intensity training may improve exercise capacity and cardiac function of patients with prior myocardial infa rct ion We investigated the effects of different training frequencies on maximum isometric voluntary contraction ( MVC ) force and plasma concentrations of muscle proteins during the early phase of eccentric training . MVC and plasma concentrations of creatine kinase ( CK ) and slow-twitch skeletal ( cardiac beta-type ) myosin heavy chain ( MHC ) fragments were measured before and 4 and 7 d after performing the first and last training task . Training tasks , which comprised 70 high-force eccentric contractions involving the thigh muscles ( single leg ) , were performed under supervision in three groups ( A , B , C ) at the beginning and at the end of the study period ( 7 wk ) . In addition , groups A ( N = 10 ) and B ( N = 10 ) trained during the study period starting 1 wk after the first training task . Group A performed one training task once a week for 5 wk and group B ( N = 10 ) twice a week for 2 wk and three times a week during the subsequent 3 wk . In all three groups the first training task result ed in delayed CK and MHC peaks and decrements in MVC , which were comparable ( P > 0.05 ) . Only training regimen B result ed in a significant increase in the MVC . Compared with the first training task training regimens , A and B significantly ( P < 0.01 ) reduced the increase in serum muscle protein and muscle function impairment . The responses to the last training task did not differ significantly between groups A and B. In group C the responses after the second training task did not differ significantly from those observed after the first task . Our results suggest that , compared with group A , additional eccentric exercise in group B is the essential basis for the increase in muscle strength during the early phase of eccentric training without further benefits for muscular adaptation . In group C we found no muscular adaptation The effectiveness of 2 different exercise programs in the convalescent phase of acute myocardial infa rct ion ( AMI ) was assessed . One hundred and five patients with AMI were enrolled for one of these 2 non-supervised home exercise programs immediately after discharge from the hospital . Before discharge and one month later , they underwent submaximal grade d treadmill exercise tests with the application of expiratory gas analysis . All patients were assigned to perform 2 km of walk-jog exercise daily for one month . The heart rate during exercise , duration of exercise and the total steps during 24 hrs were measured . Eighty patients ( group A ) underwent the exercise program in which their heart rates were maintained at 100 - 110 beats/min during exercise ; while 25 patients ( group B ) underwent the other program in which their heart rates were maintained at 90 - 100 % of those obtained at their anaerobic threshold ( AT ) . The ventilatory AT was calculated by the st and ard technique using the Horizon System . In group A , AT increased from 13.4 ml/min/kg to 15.1 ml/min/kg ( p < 0.01 ) after the exercise program and in group B , from 12.8 ml/min/kg to 14.9 ml/min/kg ( p < 0.01 ) . In group B , AT increased in all patients , while it remained unchanged in 30 % of the patients in group A ( p < 0.01 ) . In conclusion , a non-supervised home exercise program can be effective and easily instituted for rehabilitation in a convalescent phase of AMI . The program using 90 - 100 % of the heart rates at the anaerobic threshold seemed to be more suitable for obtaining better effects on exercise tolerance than that using 100 - 110/min heart rate OBJECTIVES The objective of this study is to determine if exercise increases joint symptoms in older adults with a history of arthritis or produces symptoms in older adults without such history . In addition , we examine whether joint symptoms explain the large observed variation in strength gain in older adults undergoing vigorous strength training exercise , and report the incidence of musculoskeletal injuries upon initiation of an exercise program . DESIGN A population -based , single blinded , r and omized controlled trial with three exercise groups and one control group . SETTING A large urban health maintenance organization . PARTICIPANTS Older men and women ( N = 105 ) aged 68 to 85 , with leg strength below the 50th percentile for their age , sex , height , and weight and without neuromuscular disease or active cardiovascular disease . INTERVENTIONS Supervised exercise in 1-hour sessions , three times each week , for 24 to 26 weeks . One exercise group did strength training ( ST ) using weight machines ( n = 25 ) ; another group did endurance training ( ET ) using stationary cycles ( n = 25 ) ; and the third group did combined strength training and endurance training ( ST+ET ) ( n = 25 ) . The control group ( n = 30 ) received no intervention . MEASUREMENTS Strength was measured at the ankle , knee , hip , and elbow using an isokinetic dynamometer . Joint symptoms were rated on a 6-point scale ( 0 = none , 5 = severe ) . Arthritis severity was based on self-reported use of arthritis medication . Health status was measured with subscales of the SF-36 and Sickness Impact Profile ( SIP ) . RESULTS Joint symptoms fluctuated over time in all exercise groups , but they did not improve or worsen significantly in any group . The physical dimension of the SIP and SF-36 subscale scores , including Bodily Pain Scores , did not change over time in any group . Subjects with arthritis and joint symptoms gained as much strength with strength training as did subjects without joint symptoms . Adjustment for age , gender , baseline strength , adherence , and exercise group did not affect this finding . The rate of minor musculoskeletal injuries was 2.2 injuries per 1000 exercise hours . CONCLUSIONS Moderate intensity stationary cycle exercise and vigorous intensity strength training do not appear to produce or exacerbate joint symptoms in older adults . Joint symptoms did not explain the large variation in gains in strength in older adults participating in a st and ardized strength training exercise program . Musculoskeletal injuries occurred relatively infrequently , and no major injuries occurred . In evaluating joint pain that occurs in older adults in well regulated exercise programs , clinicians should consider other etiologies before attributing pain to exercise per se OBJECTIVE : To investigate the effect of an exercise training program on lipid profile in correlation with DHEA level and body weight and body composition in type 2 diabetic men . DESIGN : Longitudinal , controlled clinical intervention study with exercise training consisting of an 8 week supervised program of aerobic exercise ( 75 % VO2 peak , 45 min ) , twice a week and intermittent exercise , once a week , on a bicyle ergometer . SUBJECTS : Sixteen men ( age 45.4±7.2 y ( mean±s.d . ) , HbA1c 8.15±1.7 % , body mass index ( BMI ) 29.6±4.6 kg/m2 ) were r and omly divided into two groups : trained group ( n=8 ) and control group ( n=8 ) . MEASUREMENTS : Lipid , apo- and lipoprotein and DHEA concentrations . Cross-sectional areas of subcutaneous and visceral adipose tissue and mid-thigh muscle by magnetic resonance imaging . RESULTS : Training decreased visceral ( 153.25±38.55 vs 84.20±21.30 cm2 , P<0.001 ) , subcutaneous ( 241.55±49.55 vs 198.00±39.99 cm2 , P<0.001 ) adipose tissue area and triglyceride levels ( 2.59±1.90 vs 1.79±1.08 nmol/l , P<0.05 ) and increased mid-thigh muscle cross-sectional area ( 148.30±36.10 vs 184.35±35.85 cm2 , P<0.001 ) , and DHEA levels ( 11.00±3.10 vs 14.25±4.10 nmol/l , P<0.05 ) with no modification in body weight . Changes in triglycerides were negatively correlated with changes in DHEA ( r=−0.81 , P=0.03 ) . This correlation was independent of changes in abdominal fat distribution . CONCLUSION : Training decreases abdominal fat depots , improves muscular mass and affects favourably triglyceride and DHEA levels . Changes in triglycerides and DHEA were inversely related BACKGROUND The study tested the effect of strength and endurance training on gait , balance , physical health status , fall risk , and health services use in older adults . METHODS The study was a single-blinded , r and omized controlled trial with intention-to-treat analysis . Adults ( n = 105 ) age 68 - 85 with at least mild deficits in strength and balance were selected from a r and om sample of enrollees in a health maintenance organization . The intervention was supervised exercise ( 1-h sessions , three per week , for 24 - 26 weeks ) , followed by self-supervised exercise . Exercise groups included strength training using weight machines ( n = 25 ) , endurance training using bicycles ( n = 25 ) , and strength and endurance training ( n = 25 ) . Study outcomes included gait tests , balance tests , physical health status measures , self-reported falls ( up to 25 months of follow-up ) , and inpatient and outpatient use and costs . RESULTS There were no effects of exercise on gait , balance , or physical health status . Exercise had a protective effect on risk of falling ( relative hazard = .53 , 95 % CI = .30-.91 ) . Between 7 and 18 months after r and omization , control subjects had more outpatient clinic visits ( p < .06 ) and were more likely to sustain hospital costs over $ 5000 ( p < .05 ) . CONCLUSIONS Exercise may have beneficial effects on fall rates and health care use in some subgroups of older adults . In community-living adults with mainly mild impairments in gait , balance , and physical health status , short-term exercise may not have a restorative effect on these impairments The present study compared the different health effects of 6 months ' endurance training at two exercise intensities . Seventy-five nonsmoking , sedentary men were r and omly assigned to either a home-based , unsupervised exercise program of 4 x 30 min/wk jogging at an intensity of 75 % VO2max ( n = 28 ) , or of 6 x 30 min/wk walking at an intensity of 50 % VO2max ( n = 28 ) , or to an inactive control group ( n = 19 ) . Exercise adherence and injuries related to exercise training as well as changes in endurance capacity , body fat , and serum lipids were assessed . After 6 months , joggers and walkers showed a similar increase in VO2max as measured by a maximal bicycle ergometer test ( 2.9 + /- 4.1 ml/kg min , P < 0.01 and 2.5 + /- 5.7 ml/kg min , P < 0.5 , respectively ) . There were no significant changes in blood lipids in either group , although results revealed a significant association between the amount of training ( i.e. , kilometers exercised ) and the increase in high-density lipoprotein-cholesterol ( HDL-C ) in joggers ( Pearson 's r = 0.42 , P < 0.05 ) . In walkers , a significant association between the amount of exercise and the decrease in sum of skinfolds and the waist-hip ratio was observed ( Pearson 's r = -0.48 and -0.45 , P < 0.05 for both ) . The adherence rate was similar for both training groups with respect to the prescribed intervention goal with an average of 90 + /- 41 min/wk ( joggers ) and 121 + /- 72 min/wk ( walkers ) spent on endurance training . ( ABSTRACT TRUNCATED AT 250 WORDS Objective : To investigate effect of initial severity of arm impairment on response to additional physiotherapy for the arm after stroke . Design : In this controlled trial , patients were r and omized into one of three groups : routine physiotherapy ( RPT ) patients received no additional physiotherapy ; qualified physiotherapy ( QPT ) patients received additional treatment from a qualified physiotherapist ; assistant physiotherapy ( APT ) patients received additional treatment from a trained supervised assistant . Comparisons between the whole groups found no significant differences and have been reported elsewhere . In a post hoc analysis , the groups were subdivided according to severity of initial arm impairment . The subgroups were then compared . Setting : A general hospital with acute and rehabilitation facilities for stroke patients . Subjects : Patients ( n= 282 ) between one and five weeks after stroke . Interventions : Ten hours additional physiotherapy were given over a five-week period . The treatment approach reflected current usual British practice . ‘ Blind ’ outcome assessment was performed after intervention , and at three and six months after stroke . Main outcome measures : Rivermead Motor Assessment Arm Scale , Action Research Arm Test . Results : In more severe patients , no benefits of additional treatment were detected . In less severe patients , significant benefits were found in those who completed treatment with the trained assistant . However , a considerable number of patients did not complete the additional treatment . The content of treatment differed between the QPT and APT groups . Treatment of less severe APT patients emphasized repetitive supervised practice of movements and functional tasks . No significant effects of additional treatment were found in terms of shoulder pain or spasticity . Conclusions : Regardless of whether additional physiotherapy was given or not , patients with severe arm impairment improved very little in arm function . Enabling adaptation to loss of arm function may be an appropriate rehabilitation strategy for some patients . Trends in the data confirm findings of some previous studies that intensive treatment for patients with some motor recovery of the upper limb is effective . Following patient assessment and treatment planning by a qualified physiotherapist , it may be appropriate for guidance of repetitive practice of motor and functional tasks to be delegated to trained and closely supervised assistant staff PURPOSE This study was performed to test the effectiveness of a formal supervised exercise program against a home-based exercise program for both walking ability and quality of life endpoints . METHODS Patients with arterial claudication were r and omized to either a 12-week supervised exercise program ( SUPEX ) with weekly lectures relating to peripheral vascular disease or to a home exercise group ( HOMEX ) who attended an identical lecture program and received weekly exercise instruction . The study population included 29 men and 26 women , with a mean age of 69.1 + /- 8.1 years . Forty-seven patients completed the 12-week program , 46 were available for testing at completion , and 38 for 6-month testing . Claudication pain time ( CPT ) and maximum walking time ( MWT ) on a progressive treadmill exercise test were assessed at baseline , program completion , and 6 months . The Medical Outcomes Study Short Form-36 ( SF-36 ) was administered at these intervals to assess effects on quality of life . RESULTS Each group improved ( p < 0.001 ) in both CPT and MWT at the completion of the 12-week program , which was sustained at the 6-month follow-up . Increase in HOMEX CPT from baseline ( 3.6 + /- 2.73 minutes ) to 6-month follow-up ( 6.6 + /- 3.17 minutes ) was less than for the SUPEX group ( 3.8 + /- 2.74 to 11.2 + /- 4.02 minutes , respectively ) ; similar results were obtained for MWT . At both completion and 6 months , there was a significant intergroup difference for CPT and MWT ( p < 0.004 ) favoring SUPEX . For both groups , measures of health perception based on the SF-36 demonstrated improvement ( p < 0.002 ) in Physical Function Subscale , Bodily Pain Subscale , and Physical Composite Score . There were no between-group differences on the subsets of the SF-36 at the three assessment intervals . CONCLUSIONS Supervised exercise programs provide superior increased walking ability in the noninterventional therapy of arterial claudication , and both supervised and home based exercise therapy result in improved SF-36 functional measures . The lack of intergroup differences in these measures may be a result of the high degree of interaction with healthcare providers in the HOMEX group . Although a supervised program results in optimal walking benefits , a highly structured home-based program provides similar functional improvement and may be a satisfactory alternative for patients with lesser walking requirements OBJECTIVE : To investigate the effect of a six-months training program on changes in body weight and lipid concentrations , and their interrelationship in elderly people . DESIGN : Intervention study . The elderly subjects were r and omly assigned to a control group or one of two supervised aerobic training groups , either all round activities or ergometer cycling , both exercising 3–4 times a week for six months . SUBJECTS : 229 elderly men and women , aged 60–80 y. MEASUREMENTS : Various fatness parameters by anthropometry , serum lipids and peak power output . RESULTS : During the intervention , no significant changes were observed in weight or body fatness in subjects of the training groups . Serum high density lipoprotein ( HDL ) , low density lipoprotein ( LDL ) and total cholesterol and triglycerides tended to change in a favourable direction in the elderly of the intervention groups , but only triglyceride concentration in women of the cycle ergometer group ( mean difference with controls : −0.24 mmol/L , 95 % confidence interval ( CI ) : −0.45 , −0.03 ) and total serum cholesterol and HDL-cholesterol concentrations in subjects of the all-round activity group , ( −0.32 mmol/L , 95 % CI : −0.63 , −0.01 and −0.15 mmol/L , 95 % CI −0.25 , −0.05 , respectively ) were significantly reduced as compared to controls . Regression analysis showed that the intervention-control difference in change of all lipids was independent of changes in weight , body fat and previous engagement in sport activity . CONCLUSION : Regular physical exercise in an elderly population result ed in favourable changes in serum lipid concentrations that were not significant , but no change in body weight or fatness . Change in lipid concentration could not be attributed to change in weight or body fat OBJECTIVE To determine the effects of structured exercise programs on self-reported disability in older adults with knee osteoarthritis . SETTING AND DESIGN A r and omized , single-blind clinical trial lasting 18 months conducted at 2 academic medical centers . PARTICIPANTS A total of 439 community-dwelling adults , aged 60 years or older , with radiographically evident knee osteoarthritis , pain , and self-reported physical disability . INTERVENTIONS An aerobic exercise program , a resistance exercise program , and a health education program . MAIN OUTCOME MEASURES The primary outcome was self-reported disability score ( range , 1 - 5 ) . The secondary outcomes were knee pain score ( range , 1 - 6 ) , performance measures of physical function , x-ray score , aerobic capacity , and knee muscle strength . RESULTS A total of 365 ( 83 % ) participants completed the trial . Overall compliance with the exercise prescription was 68 % in the aerobic training group and 70 % in the resistance training group . Postr and omization , participants in the aerobic exercise group had a 10 % lower adjusted mean ( + /- SE ) score on the physical disability question naire ( 1.71 + /- 0.03 vs 1.90 + /- 0.04 units ; P<.001 ) , a 12 % lower score on the knee pain question naire ( 2.1 + /- 0.05 vs 2.4 + /- 0.05 units ; P=.001 ) , and performed better ( mean [ + /- SE ] ) on the 6-minute walk test ( 1507 + /- 16 vs 1349 + /- 16 ft ; P<.001 ) , mean ( + /-SE ) time to climb and descend stairs ( 12.7 + /- 0.4 vs 13.9 + /- 0.4 seconds ; P=.05 ) , time to lift and carry 10 pounds ( 9.1 + /- 0.2 vs 10.0 + /- 0.1 seconds ; P<.001 ) , and mean ( + /-SE ) time to get in and out of a car ( 8.7 + /- 0.3 vs 10.6 + /- 0.3 seconds ; P<.001 ) than the health education group . The resistance exercise group had an 8 % lower score on the physical disability question naire ( 1.74 + /- 0.04 vs 1.90 + /- 0.03 units ; P=.003 ) , 8 % lower pain score ( 2.2 + /- 0.06 vs 2.4 + /- 0.05 units ; P=.02 ) , greater distance on the 6-minute walk ( 1406 + /- 17 vs 1349 + /- 16 ft ; P=.02 ) , faster times on the lifting and carrying task ( 9.3 + /- 0.1 vs 10.0 + /- 0.16 seconds ; P=.001 ) , and the car task ( 9.0 + /- 0.3 vs 10.6 + /- 0.3 seconds ; P=.003 ) than the health education group . There were no differences in x-ray scores between either exercise group and the health education group . CONCLUSIONS Older disabled persons with osteoarthritis of the knee had modest improvements in measures of disability , physical performance , and pain from participating in either an aerobic or a resistance exercise program . These data suggest that exercise should be prescribed as part of the treatment for knee osteoarthritis The effects of 12 weeks of home-based exercise training on peak oxygen consumption ( VO2 max ) in healthy sedentary middle-aged men , mean age 49 + /- 6 years , were evaluated . Twenty-one men trained at low intensity , 23 trained at high intensity and 20 were control subjects . Individually prescribed low- and high-intensity training was performed 5 times per week within a range of 42 to 60 % and 63 to 81 % of baseline VO2 max , corresponding to average heart rates of 102 to 122 and 128 to 148 beats/min , respectively . Caloric expenditure per training session approximated 350 kcal in both groups ; adherence was at least 90 % in both groups . VO2 max increased 8 % in patients who trained at low intensity , 17 % in those who trained at high intensity ( both p less than 0.001 ) , and not at all in control subjects . Low-intensity exercise training at home significantly augments functional capacity in healthy sedentary middle-aged men BACKGROUND So-called atypical depressive symptoms ( carbohydrate craving , prolonged sleep , weight gain , increased appetite ) frequently emerge in association with low illumination to which people are ordinarily exposed indoors , or even outdoors at extreme latitudes in wintertime . Our objective was to analyse the effect of physical exercise alone or combined with bright light on mood and the health-related quality of life during winter . METHODS We carried out a r and omized controlled trial on 120 indoor employees in southern Finl and between November and January . The subjects were allocated to supervised fitness training under bright ( 2500 - 4000 lx ) or ordinary ( 400 - 600 lx ) light conditions in a gym 2 - 3 times weekly for 8 weeks , or supervised relaxation training once a week over the same period as active placebo . We collected question naire data on the changes in mood and health-related quality of life after 4 and 8 weeks of training , and after 4 months follow-up . RESULTS Fitness training in bright light result ed in greater relief from atypical depressive symptoms and more vitality than in ordinary room light . Compared with relaxation alone , the former regime improved general mental health and social functioning in addition to the improvement in depressive symptoms and vitality , whereas the latter only increased vitality . CONCLUSIONS Supervised physical exercise combined with exposure to bright light appears to be an effective intervention for improving mood and certain aspects of the health-related quality of life in wintertime . This effect appears unrelated to the history of season-dependent symptoms , being noticeable among healthy individuals PURPOSE This study was performed to test the efficacy of a supervised , hospital-based exercise program compared with a home-based exercise program involving minimal supervision , for both walking ability and quality of life measures in patients with exercise-limiting intermittent leg claudication . METHODS Twenty-one patients were assigned r and omly to 12 weeks of supervised exercise or to a home-based exercise group . After 12 weeks the participants in the supervised group transitioned to a home-based program . Both groups were then reevaluated at the end of 24 weeks . The initial claudication distance ( ICD ) and absolute claudication distance ( ACD ) on progressive treadmill exercise was measured at baseline , 12 weeks , and 24 weeks . Additionally , self-reported quality of life status was evaluated using the MOS SF-36 question naire . RESULTS Each group improved ( P < 0.01 ) ACD from baseline to 12 weeks , which was sustained at the 24-week follow-up . Both groups experienced similar long-term improvements ( P < 0.05 ) in ACD ( 521.5 + /- 253.4 meters to 741.9 + /- 365.6 meters for the supervised group , 532.2 + /- 263.5 meters to 715.0 + /- 394.4 meters in the home group , P not significant , between groups ) . The supervised group experienced a greater improvement ( P < 0.01 ) in the ICD after 12 weeks than the home group but not at 24 weeks . The on-site group also experienced significant improvements in ICD after 24 weeks ( P < 0.05 ) . Neither group manifested an improvement in self-reported physical function or mental health as assessed by the MOS SF-36 . CONCLUSION A structured exercise program was more effective in improving the ICD over a 24-week period than a less formal , home-based program . However , if patients are screened properly and receive adequate instruction , a home-based program can be a safe , low-cost alternative providing similar long-term ( 24 weeks ) exercise benefits in ACD BACKGROUND --Pulmonary rehabilitation has been shown to have short term subjective and objective benefits for patients with chronic obstructive pulmonary disease ( COPD ) . However , appropriately controlled studies have not previously been performed , nor have the benefits of different types of continuation programme for rehabilitation been investigated . Both these problems have been addressed in a single study of the long term effects of once monthly physiotherapy versus once weekly physiotherapy at home after a comprehensive home rehabilitation programme on quality of life and exercise tolerance in patients with COPD . METHODS --Thirty six patients with severe airways obstruction ( mean SD ) forced expiratory volume in one second ( FEV1 ) 1.3(0.4 ) 1 , FEV1/inspiratory vital capacity ( IVC ) 37.2(7.9)% ) were studied . Twenty three patients followed a rehabilitation programme at home for 18 months consisting of physiotherapy and supervision by a nurse and general practitioner . During the first three months all 23 patients visited the physiotherapist twice a week for a 0.5 hour session . Thereafter , 11 patients ( group A ) received a session of physiotherapy once weekly while 12 patients ( group B ) received a session of physiotherapy once a month . The control group C ( 13 patients ) received no rehabilitation at all . Quality of life was assessed by the Chronic Respiratory Question naire , exercise tolerance by the six minute walking distance , and lung function by FEV1 and IVC . Outcome measures were assessed at baseline and at three , six , 12 , and 18 months . RESULTS --Long term improvements in quality of life were found in patients in groups A and B , but not in those in group C compared with baseline , but these only reached significance in group B at all time points . Patients in group B had a higher quality of life than those in group C only at three and 12 months . There was a decrease in both six minute walking distance ( at 12 and 18 months ) and IVC ( at three , 12 , and 18 months ) in patients in group C compared with the baseline measurement . Between groups analysis showed no differences for six minute walking distance , FEV1 , and IVC . CONCLUSIONS --This study is the first to show that rehabilitation at home for three months followed by once monthly physiotherapy sessions improves quality of life over 18 months . The change in quality of life was not associated with a change in exercise tolerance PURPOSE In patients with intermittent claudication ( IC ) a structured walking exercise program improves exercise performance . However , few studies have evaluated the effects of exercise training on functional status during daily activities . We hypothesized that a supervised exercise training program would improve functional status in patients with IC , with 24 weeks of training more beneficial than 12 weeks . A secondary aim was to evaluate the effects of strength training and combinations of strength and treadmill training on functional status . METHODS Twenty-nine men with disabling IC were r and omized to 12 weeks of either supervised treadmill training ( 3 hr/wk at a work intensity sufficient to produce claudication ) , strength training ( 3 hr/wk of resistive training of six muscle groups of each leg ) , or to a nonexercising control group . Functional status was assessed by question naires characterizing walking ability ( Walking Impairment Question naire , WIQ ) , habitual physical activity level ( Physical Activity Recall , PAR ) , and physical , social , and role functioning , well-being , and overall health ( Medical Outcomes Study SF-20 , MOS ) . Patients alos had their activity levels monitored with an activity monitor ( Vitalog ) . RESULTS After 12 weeks of treadmill training PAR scores increased by 48 metabolic equivalent hr/wk , the MOS physical functioning score by 24 percentage points , and the number of bouts of walking activity measured by the Vitalog by 4.5 bouts/hr ( all p < 0.05 ) . No changes were seen in WIQ scores . After 12 additional weeks of treadmill training improvements initially observed in the PAR , MOS , and Vitalog scores were maintained , and in addition the ability to walk distances ( WIQ ) improved by 31 percentage points , and the IC severity score had improved by 29 percentage points ( both p < 0.05 ) . After 12 weeks of strength training patients improved their WIQ walking speed , stair climbing scores , and MOS well-being scores with no other changes in functional status . Subjects in the control group did not improve functional status by any measure . Twelve weeks of treadmill training after the strength training program maintained WIQ walking speed scores , and activity level defined by Vitalog improved . Twelve weeks of combined treadmill and strength training after the control period had no effect on functional status . CONCLUSIONS A supervised treadmill training program improved functional status during daily activities , with 24 weeks more effective than 12 . In addition , treadmill training alone was more effective in improving functional status in patients with IC than strength training or combinations of the training modalities This study investigated the effectiveness of experiential cross-training in a team context for team decision-making under time stress in a simulated naval surveillance task . It was hypothesized that teams whose members explicitly experience all team positions will perform better under time pressure due to a better shared Team Interaction Model ( Cannon-Bowers et al. 1993 ) . In addition , it was posited that experiential cross-training would reduce the negative effect of member reconfiguration that can occur in certain military situations . Three groups of teams participated in this study ( cross-trained , reconfigured and control ) . The experiment involved three team training sessions , followed by three time-stressed exercise sessions . During training , one group of teams was cross-trained ( CT ) by asking each member to perform an entire session at each of the three team positions . Member reconfiguration ( where each member was shifted to another 's position ) was unexpectedly introduced at the first of the exercise sessions for the CT group and for another group ( reconfigured ) that had not been cross-trained . A third ( control ) group was neither cross-trained nor reconfigured . During training , the performance of non-CT teams improved more quickly than that of CT teams . During the exercise , the CT group did not achieve the level of performance of the control teams . The immediate effect of team member reconfiguration was to de grade performance significantly for the non-CT teams , but not for the CT teams . The findings are discussed in terms of the multiple mental models ' view of team performance ( Cannon-Bowers et al. 1993 ) and the authors discuss the relative utility of crosstraining when overall training time is fixed BACKGROUND In short-term studies , diet and exercise both improve insulin sensitivity . OBJECTIVE To determine the effects of a 48-week supervised diet and exercise program on weight and insulin sensitivity after initial weight loss and weight maintenance , and then subsequent weight regain over 96 weeks . METHODS Forty-five obese women were r and omly assigned to 1 of 3 treatment groups : ( 1 ) diet alone , ( 2 ) diet and aerobic training , and ( 3 ) diet and strength training . All subjects received the same 48-week group behavior modification program and diet ( approximately 3879 kJ/d [ approximately 925 kcal/d ] for the first 16 weeks ; approximately 6276 kJ/d [ approximately 1500 kca/d ] thereafter ) . Exercising subjects were provided 3 supervised exercise sessions per week for the first 28 weeks and 2 sessions weekly until week 48 . During weeks 48 to 96 , subjects were unsupervised . Oral glucose tolerance tests were performed at baseline and weeks 16 , 24 , 44 , and 96 . RESULTS Subjects across the 3 conditions achieved a mean weight loss of 13.8 kg by week 16 , which was associated with decreased insulin levels ( 61.8 % of baseline ) There were no significant differences among groups in changes in body mass index , which is a measure of weight in kilograms divided by the square of the height in meters , weight , glucose tolerance , or insulin levels at weeks 16 , 24 , and 44 . No additional beneficial effect of aerobic or strength exercise on insulin resistance , as reflected by serum insulin levels before and after a glucose load , was demonstrated . The 22 subjects who were studied at week 96 maintained a loss of approximately 10 % of initial weight . Insulin levels , however , had returned to pretreatment levels . CONCLUSIONS This study confirms the beneficial effect of weight reduction on hyperinsulinemia in obese individuals . Participation in supervised exercise did not result in additional improvement in weight loss or insulin sensitivity . We also observed a marked increase in insulin levels with only partial weight regain . Determining the amount of sustained weight loss necessary for continued improvement in insulin sensitivity will require further study BACKGROUND Although inactivity is an important contributor to impaired functioning and disability with age , little is known concerning how improvements in physical functioning and well-being in older adults vary with the type of physical activity undertaken . METHODS One hundred three adults age 65 years and older , recruited via population -based methods , were r and omized to 12 months of community-based , moderate-intensity endurance and strengthening exercises ( Fit & Firm ) or stretching and flexibility exercises ( Stretch & Flex ) . A combination of class- and home-based exercise formats was used . Measured and self-rated physical performance along with perceived functioning and well-being were assessed pre- and postintervention . RESULTS Fit & Firm subjects showed greater 12-month improvements in both measured and self-rated endurance and strength compared to Stretch & Flex subjects . Stretch & Flex subjects reported greater improvements in bodily pain , and Stretch & Flex men evidence d greater improvements in flexibility relative to Fit & Firm subjects . Although overall exercise adherence was high in both exercise conditions ( approximately 80 % ) , subjects in both conditions showed better adherence to the home- versus class-based portions of their exercise prescriptions . CONCLUSIONS Community-based programs focusing on moderate-intensity endurance and strengthening exercises or flexibility exercises can be delivered through a combination of formats that result in improvement in important functional and well-being outcomes . This represents one of the first studies to report significant improvements in an important quality of life outcome -bodily pain-with a regular regimen of stretching and flexibility exercises in a community-based sample of older adults We hypothesized that short-term endurance training improves balance in older adults , if training involves movements that “ stress ” balance . We tested the hypothesis by looking for a dose-response relationship between movement during exercise and balance improvement . The study was a single-blinded , r and omized controlled trial . Subjects were sedentary adults ( N=106 ) aged 68–85 with at least mild deficits in balance . Exercise groups were : stationary cycle ( low movement ) , walking ( medium movement ) , and aerobic movement ( high movement ) . Subjects attended supervised exercise classes three times a week for three months , followed by self-directed exercise of any type for three months . The primary test of the hypothesis compared changes in balance after three months of supervised exercise . One balance measure ( distance walked on a six-meter narrow balance beam ) improved in the hypothesized dose-response manner ( cycle , 3 % improvement ; walking , 7 % improvement ; aerobic movement , 18 % improvement : p<0.02 , test of trend ) . Other balance measures did not improve with exercise . Only walking exercise improved gait speed ( by 5 % , p<0.02 ) and SF-36 role-physical score ( by 24 % , p<0.05 ) . VO2max improved with walking ( 18 % , p<0.004 ) and aerobic movement ( 10 % , p<0.01 ) , but improved less with cycling ( 8 % , p>0.1 ) . Leg strength improved significantly in all exercise groups . The study hypothesis was supported only for one balance measure . Only walking improved at least one measure of all major outcomes ( endurance , strength , gait , balance , health status ) , suggesting that walking is most useful for fall prevention . Cycle exercise appeared least useful Objectives . To investigate the relationships among self-efficacy , changes in self-efficacy , past exercise participation , future exercise adherence , and exercise program format . Methods . Two-year r and omized trial involving subjects ( n = 63 ) participating in an aerobic exercise program . Subjects were r and omly assigned to one of three exercise conditions : higher-intensity home-based exercise , higher-intensity class-based exercise , or lower-intensity home-based exercise . Results . Results indicated that baseline self-efficacy and exercise format had significant ( p < .02 ) , independent effects on adherence during the adoption and early maintenance phases of exercise behavior . In contrast , in predicting long-term exercise program maintenance , a significant ( p < .05 ) self-efficacy X exercise format interaction indicated that self-efficacy predicted adherence only in the supervised home-based exercise conditions . Results also suggest that baseline self-efficacy , independent of the effect of past adherence , significantly ( p < .03 ) predicted exercise adherence during the adoption phase , but not early maintenance phase , of exercise behavior . Finally , adherence change during the adoption phase of exercise behavior significantly ( p < .04 ) predicted Year-one levels of self-efficacy even after adjusting far the effect of baseline self-efficacy . Conclusions . These results suggest that exercise program format as well as an individual 's initial cognitive and behavioral experiences in an exercise program play significant roles in determining exercise adherence The effects of the intensity of exercise training on cardiorespiratory variables were investigated in a consecutive series of men with recent ( median 8 weeks ) acute myocardial infa rct ion . Forty-five patients were r and omly assigned either to a high- ( 65 to 75 % maximum oxygen consumption rate [ VO2max ] ) or to a low-intensity ( less than 45 % VO2max ) exercise group . Patients engaged in medically supervised aerobic training 3 sessions a week for 12 weeks . With training , mean VO2max significantly increased by 11 % ( 2.09 to 2.31 liters/min ) within the high group and by 14 % ( 1.93 to 2.21 liters/min ) within the low group . Differences between groups were not statistically significant . Both groups also had comparable changes in heart rate , blood pressure and double-product at submaximal and maximal workloads . Analysis of blood lipids revealed that both groups experienced a significant increase in high density lipoprotein cholesterol . There were no significant changes in total serum cholesterol or triglycerides . These findings suggest that within an unselected population of patients after acute myocardial infa rct ion referred for cardiac rehabilitation , low- and high-intensity exercise training produces relatively similar changes in cardiorespiratory variables during the initial 3 months of exercise training OBJECTIVE To determine whether diet and endurance exercise improved adiposity-related measurements in Japanese Americans with impaired glucose tolerance ( IGT ) . RESEARCH DESIGN AND METHODS This study compared the effects of an American Heart Association ( AHA ) step 2 diet ( < 30 % of total calories as fat , < 7 % saturated fat , 55 % carbohydrate , and < 200 mg cholesterol daily ) plus endurance exercise for 1 h three times a week ( treatment group ) with an AHA step 1 diet ( 30 % of total calories as fat , 10 % saturated fat , 50 % carbohydrate , and < 300 mg cholesterol ) plus stretching exercise three times a week ( control group ) on BMI , body composition ( % fat ) , and body fat distribution at 6 and 24 months of follow-up in 64 Japanese American men and women with IGT , 58 of whom completed the study . RESULTS At 6 months , the treatment group showed significantly greater reduction in percent , body fat ( -1.4 + /- 0.4 vs. -0.3 + /- 0.3 % ) ; BMI ( -1.1 + /- 0.2 vs. -0.4 + /- 0.1 kg/m(2 ) ) ; subcutaneous fat by computed tomography at the abdomen ( -29.3 + /- 4.2 vs. -5.7 + /- 5.9 cm(2 ) ) , thigh ( -13.2 + /- 3.6 vs. -3.6 + /- 3.0 cm(2 ) ) , and thorax ( -19.6 + /- 3.6 vs. -8.9 + /- 2.6 cm(2 ) ) ; and skinfold thickness at the bicep ( -2.0 + /- 0.6 vs. 1.1 + /- 0.6 mm ) and tricep ( -3.7 + /- 0.8 vs. -0.9 + /- 0.6 mm ) , which continued despite moving to home-based exercise for the last 18 months . CONCLUSIONS Diet and endurance exercise improved BMI , body composition , and body fat distribution and , thus , may delay or prevent type 2 diabetes in Japanese Americans with IGT A pilot trial was conducted to test adherence to specific lifestyle interventions among Pima Indians of Arizona , and to compare them for changes in risk factors for diabetes mellitus . Ninety-five obese , normoglycaemic men and women , aged 25 - 54 years , were r and omized to treatments named ' Pima Action ' ( Action ) and ' Pima Pride ' ( Pride ) , which were tested for 12 months . Action involved structured activity and nutrition interventions , and Pride included unstructured activities emphasizing Pima history and culture . Adherence to interventions , changes in self-reported activity and diet , and changes in weight , glucose concentrations , and other risk factors were assessed regularly . Thirty-five eligible subjects who had declined r and omization were also followed as an ' observational ' group and 22 members of this group were examined once at a median of 25 months for changes in weight and glucose concentration . After 12 months of intervention , members of both intervention groups reported increased levels of physical activity ( median : Action 7.3 h month(-1 ) , Pride 6.3 h month(-1 ) , p < 0.001 for each ) , and Pride members reported decreased starch intake ( 28 g , p = 0.008 ) . Body mass index , systolic and diastolic blood pressures , weight , 2-h glucose and 2-h insulin had all increased in Action members ( p < 0.003 for each ) , and waist circumference had decreased in Pride members ( p = 0.05 ) . Action members gained more weight than Pride members ( 2.5 kg vs 0.8 kg , p = 0.06 ) , and had a greater increase in 2-h glucose than Pride members ( 1.33 mM vs 0.03 mM , p = 0.007 ) . Members of the observational group gained an average of 1.9 kg year(-1 ) in weight and had an increase of 0.36 mM year(-1 ) in 2-h glucose . Sustaining adherence in behavioural interventions over a long term was challenging . Pimas may find a less direct , less structured , and more participative intervention more acceptable than a direct and highly structured approach OBJECTIVE To evaluate the effectiveness of physicians vs physical therapists as instructors of the musculoskeletal examination to second year medical students . METHODS A r and omized trial conducted over 3 consecutive years in a physical diagnosis course at The University of North Carolina . During the first ( baseline ) year , medical students received education about the musculoskeletal examination from a lecture and supervision by clinical preceptors . This increased in the second and third ( intervention ) years where r and om halves of each class received supplementary clinical instruction which included a structured manual , a videotape , and supervised practice with either general internal medicine physicians or physical therapists . Outcomes were measured from student performance on a practical test of clinical skills , and by written student evaluations of the supplementary instruction . RESULTS As measured on the clinical examination , performance during the intervention years improved over that during the baseline year in both intervention groups . Measures of medical students ' clinical skills did not correlate with measures of academic aptitude . CONCLUSIONS Clinical education about the musculoskeletal examination should be structured and systematic . Medical students prefer clinical education that is active , provides clear directions , and gives them performance feedback OBJECTIVE To determine the effects of center-based exercise on physical performance in older persons at risk for decline in physical functioning . DESIGN R and omized controlled trial . SETTING Senior centers . PARTICIPANTS A total of 155 community-dwelling persons , 78.7 % women , ages 70 years and older ( mean + /- st and ard deviation , 77.0+/-4.5y ) , with mobility impairments . INTERVENTION Intervention volunteers ( n=80 ) exercised at a center ( endurance , strength , balance , flexibility ) 3 times weekly , for months 1 to 6 ; once weekly , for months 7 to 12 with home exercise 2 sessions a week ; and at home only , for months 13 to 18 . Home control volunteers ( n=75 ) were instructed in home endurance exercise . MAIN OUTCOME MEASURES MacArthur battery , Physical Performance Test ( PPT-8 ) , and 6-Minute Walk Test ( 6MWT ) at baseline and 3 , 6 , 12 , and 18 months . RESULTS MacArthur battery scores improved in intervention compared with home control at 3 , 6 , and 12 months ( repeated- measures analysis of variance : group x time , P<.05 ) but not 18 months . PPT-8 and 6MWT did not improve . Intervention group assignment , younger age , and better baseline physical function and self-perceived health were independent predictors of long-term MacArthur battery score improvement . CONCLUSIONS Compared with home control , center-based exercise improved gait , chair rise time , and balance over 1 year . Improvements were not sustained with transition to home exercise for months 13 to 18 . Classes may be necessary to maintain improvements in older persons attending center-based exercise OBJECTIVE To examine the short- and long-term effects of an outpatient pulmonary rehabilitation program for COPD patients on dyspnea , exercise , health-related quality of life , and hospitalization rate . SETTING Secondary -care respiratory clinic in Barcelona . METHODS We conducted a r and omized controlled trial with blinding of outcome assessment and follow-up at 3 , 6 , 9 , 12 , 18 , and 24 months . Sixty patients with moderate to severe COPD ( age 65 + /- 7 years ; FEV(1 ) 35 + /- 14 % ) were recruited . Thirty patients r and omized to rehabilitation received 3 months of outpatient breathing retraining and chest physiotherapy , 3 months of daily supervised exercise , and 6 months of weekly supervised breathing exercises . Thirty patients r and omized to the control group received st and ard care . RESULTS We found significant differences between groups in perception of dyspnea ( p < 0.0001 ) , in 6-min walking test distance ( p < 0.0001 ) , and in day-to-day dyspnea , fatigue , and emotional function measured by the Chronic Respiratory Question naire ( p < 0 . 01 ) . The improvements were evident at the third month and continued with somewhat diminished magnitude in the second year of follow-up . The PR group experienced a significant ( p < 0.0001 ) reduction in exacerbations , but not the number of hospitalizations . The number of patients needed to treat to achieve significant benefit in health-related quality of life for a 2-year period was approximately three . CONCLUSION Outpatient rehabilitation programs can achieve worthwhile benefits that persist for a period of 2 years Participation in a st and ard-length outpatient cardiac rehabilitation program ( CRP ) for 3 months is known to result in positive changes in body composition , functional capacity , and blood lipids in patients with coronary artery disease . However , there has been little attempt to compare patients who remain active in a formal CRP for an extended length of > 1 year with patients who exit after a st and ard length of 3 months . Consequently , 50 patients underwent a series of tests including a maximal grade d exercise treadmill test , assessment of body composition , and fasting blood lipid analysis , at entry to CRP and after a follow-up period that ranged from 1 to 5 years . All patients participated in a st and ard multidisciplinary cardiac rehabilitation program for 3 months . Twenty-five patients discontinued participation after 3 months and received no other contact from the program staff until follow-up , whereas 25 patients remained active in the program until follow-up . After statistically adjusting for baseline differences between the groups , significant differences were observed between the extended- and st and ard-length groups at follow-up for body weight ( 177 vs 183 lbs ) , percent fat ( 22 % vs 24 % ) , METS ( 10.5 vs 8.4 ) , high-density lipoprotein level cholesterol ( 44 vs 39 mg/dl ) , total cholesterol/high-density lipoprotein ratio ( 5.2 vs 6.1 ) , and triglycerides ( 134 vs 204 mg/dl ) , respectively . No significant differences in the adjusted means were observed between the groups at follow-up for total cholesterol ( 209 vs 219 mg/dl ) and low-density lipoprotein cholesterol ( 136 vs 138 mg/dl ) . Data from this study demonstrate the efficacy of extended participation in CRP on body composition , functional capacity , and blood lipids . Greater efforts need to be directed at retaining patients in low-cost , center-based maintenance programs and at extending monitoring of patients exiting st and ard length CRPs CONTEXT If physical inactivity , obesity , and smoking status prove to contribute significantly to increased health care charges within a short period of time , health plans and payers may wish to invest in strategies to modify these risk factors . However , few data are available to guide such re source allocation decisions . OBJECTIVE To examine the relationship of modifiable health risks to subsequent health care charges after controlling for age , race , sex , and chronic conditions . DESIGN , SETTING , AND PARTICIPANTS Cohort study of a stratified r and om sample of 5689 adults ( 75.5 % of total sample of 7535 ) aged 40 years or older who were enrolled in a Minnesota health plan and completed a 60-item question naire . MAIN OUTCOME MEASURE Re source use as measured by billed health care charges from July 1 , 1995 , to December 31 , 1996 , compared by health risk ( physical activity , body mass index [ BMI ] , and smoking status ) . RESULTS The mean annual per patient charge in the total study population was $ 3570 ( median , $ 600 ) , and 15 % of patients had no charges during the study period . After adjustment-for age , race , sex , and chronic disease status , physical activity ( 4.7 % lower health care charges per active day per week ) , BMI ( 1.9 % higher charges per BMI unit ) , current smoking status ( 18 % higher charges ) , and history of tobacco use ( 25.8 % higher charges ) were prospect ively related to health care charges over 18 months . Never-smokers with a BMI of 25 kg/m2 and who participated in physical activity 3 days per week had mean annual health care charges that were approximately 49 % lower than physically inactive smokers with a BMI of 27.5 kg/m2 . CONCLUSIONS Our data suggest that adverse health risks translate into significantly higher health care charges within 18 months . Health plans or payers seeking to minimize health care charges may wish to consider strategic investments in interventions that effectively modify adverse health risks OBJECTIVE The role of exercise in the prevention of falls and fall-related injuries among elderly persons is unclear . The objective of this study was to assess the response to an exercise-based rehabilitation program intended to improve balance and mobility and reduce or prevent falls . DESIGN Pretest-posttest experimental design with repeated measures at baseline , immediately postintervention , and 6 months postintervention . To assess the effect of repeated exposure to our main outcome measure ( the obstacle course ) , half of the participants ( r and omly selected ) were allowed to practice on the obstacle course . SETTING A veterans affairs medical center . PARTICIPANTS Elderly , ambulatory , community-dwelling volunteers recruited from among local out patients at our medical center . INTERVENTION Sixty-five volunteers completed a 6-week supervised low to moderate intensity program of stretching , postural control , endurance walking , and coordination exercises design ed to improve balance and mobility . Participants were divided into 2 groups : 34 participants who did not practice on the obstacle course during their exercise program and 31 participants who practice d on the obstacle course in addition to their otherwise identical exercise program . MAIN OUTCOME MEASURES Performance on a functionally oriented obstacle course and self-reported falls and fall-related injuries . RESULTS No significant performance differences were found between the two groups . After intervention , mean qualitative obstacle course scores improved modestly ( 5 % ) and mean obstacle course completion time decreased by 15 % from baseline . These postintervention pairwise performance differences were clinical ly important but not statistically significant . Relative to baseline levels , postintervention falls and injuries did not change significantly . CONCLUSIONS Our exercise intervention may have the potential to improve functional performance . However , some modifications are necessary to enhance efficacy . The obstacle course may be a useful tool in the evaluation of elderly persons with balance and mobility impairment in the rehabilitation setting The purpose of this study was to determine the effects of 6 months of moderate aerobic exercise on age-dysregulated measures of T lymphocyte and natural killer ( NK ) cell number and function . Previously sedentary elderly ( age = 65 + /- 0.8 years ) subjects were r and omly assigned to supervised 3 time/week exercise intervention group ( EXC , n = 14 ) or flexibility/toning control group ( FT-CON , n = 15 ) . Fasting resting blood sample s were drawn prior to and after the 6 month intervention . The EXC group exhibited a significant ( P < 0.05 ) 20 % increase in VO2 max , whereas the FT-CON group had a smaller non-significant ( P = 0.07 ) increase ( 9 % ) . Immune results revealed that , in general , changes in immune function in response to 6 months of exercise training at an average intensity of 52 % heart rate reserve ( HRR ) were similar when compared to FT-CON who exercised at approximately 21 % HRR . There were no intervention-induced changes in total white blood cell , neutrophil , lymphocyte , monocyte , eosinophil , or basophil blood counts . Furthermore , the percentage and number of CD3 + , CD4 + and CD8 + T cells in the blood remained unchanged . There was a tendency for the percentage and number of CD4 + and CD8 + näive cells ( CD45RA+ ) to increase and for CD4 + memory cells ( CD45RO+ ) to decrease post-intervention , especially in FT-CON . Both groups exhibited a small intervention-induced increase in the T-cell proliferative response to mitogenic stimulation : the percentage change of which was higher in the EXC group at several doses of Con A. Unstimulated NK cell cytolysis versus K562 cells tended to increase ( P < 0.1 ) in the EXC group with little change in FT-CON . We conclude that 6 months of supervised exercise training can lead to nominal increases in some measures of immune function , while not affecting others , in previously sedentary elderly The short- and long-term outcome of exercise reconditioning on exercise tolerance and breathlessness scores were evaluated in a group of patients with severe chronic obstructive pulmonary disease ( COPD ) . After a combined initial program of eight weeks , the patients were r and omized into two groups : group A followed a supervised training program for another 12 weeks ; group B was discharged after this initial program and received written instructions to continue exercise training at home . The patients were evaluated at the start , after the initial eight weeks ' training , after six months , and after one year . For the total group , exercise tolerance , assessed by 12-minute walking distance , increased significantly from 784 m to 848 m ( p less than .05 ) after the initial program . Neither breathlessness scores nor spirometric data changed significantly . In group A , the increase in exercise tolerance persisted not only at the end of the continued training program but even at the end of the one-year follow-up . In group B , there was a progressive and significant decline of exercise tolerance during the one-year follow-up . Our data confirm that even in severe COPD patients , exercise tolerance can increase significantly without any change in spirometric data and without an increased tolerance for the sensation of dyspnea . A supervised training program must be continued to stabilize the obtained effects because even when an initial improvement is experienced , patients may lack motivation to continue an unsupervised training program This was a prospect i ve , r and omized evaluation of the safety and efficacy of 10 weeks of circuit weight training in patients , aged 35 to 70 years , with documented coronary artery disease . Circuit weight training refers to the performance of a series of weight-lifting exercises using a moderate load with frequent repetitions . Patients had participated in a supervised cardiac rehabilitation program for a minimum of 3 months before the study . Control patients ( n = 20 ) continued with their regular exercise consisting of a walk/jog and volleyball program , while the experimental group ( n = 20 ) substituted circuit weight training for volleyball . No sustained arrhythmias or cardiovascular problems occurred . The experimental group significantly increased treadmill time from 619 to 694 seconds while the treadmill time of the control group did not change . Strength in the experimental group increased by an average of 24 % while there was no change in the control patients . Circuit weight training appears to be safe , and to result in significant increases in aerobic endurance and musculoskeletal strength compared with traditional exercise used in cardiac rehabilitation programs This study determined the effect of a high vs low resistive inspiratory muscle interval training protocol on inspiratory muscle strength ( PImax ) , incremental inspiratory threshold loading ( Pitl ) , inspiratory muscle endurance ( IE ) , and 12-minute distance test ( 12 MD ) in severely impaired patients with COPD . We used a double-blind , two-group , repeated-measure design . Group 1 ( n = 12 ) received supervised high resistive loading at approximately 52 percent PImax and group 2 ( n = 8) received supervised low resistive loading at approximately 22 percent PImax . All subjects trained three times weekly ( progressing from 5 min per session in week 1 to 18 min per session in week 12 ) for 12 weeks . After three practice sessions , measures of PImax , Pitl , IE , and 12 MD were taken at baseline , at 4-week intervals , and within 72 h of completing the protocol . Group 1 showed significant improvement in all four dependent variables while group 2 improved in Pitl , IE , and 12 MD . The results suggest there is no significant difference between high and low resistive interval training in more severely impaired patients with COPD BACKGROUND As exercise is associated with favorable health outcomes , impaired older adults may benefit from specialized exercise interventions to achieve gains in function . The purpose of this study was to determine the added benefit of a spinal flexibility-plus-aerobic exercise intervention versus aerobic-only exercise on function among community-dwelling elders . METHODS We employed a r and omized clinical trial consisting of 3 months of supervised exercise followed by 6 months of home-based exercise with telephone follow-up . A total of 210 impaired males and females over age 64 enrolled in this study . Of these , 134 were r and omly assigned to either spinal flexibility-plus-aerobic exercise or aerobic-only exercise , with 116 individuals completing the study . Primary outcomes obtained at baseline , after 3 months of supervised exercise , and after 6 months of home-based exercise included : axial rotation , maximal oxygen uptake ( VO2max ) ; functional reach , timed-bed-mobility ; and the Physical Function Scale ( PhysFunction ) of the Medical Outcomes Study SF-36 . RESULTS Differences between the two interventions were minimal . Overall change scores for both groups combined indicated significant improvement for : axial rotation ( p=.001 ) , VO2max ( p=.0001 ) , and PhysFunction ( p=.0016 ) . Secondary improvements were noted for overall health ( p=.0025 ) and reduced symptoms ( p=.0008 ) . Differences between groups were significant only for VO2max ( p=.0014 ) at 3 months with the aerobic-only group improving twice as much in aerobic capacity as the spinal flexibility-plus-aerobic group . Repeated measures indicated both groups improved during the supervised portion of the intervention but tended to return toward baseline following the home-based portion of the trial . CONCLUSIONS Gains in physical functioning and perceived overall health are obtained with moderate aerobic exercise . No differential improvements were noted for the spinal flexibility-plus-aerobic intervention BACKGROUND AND PURPOSE Much controversy exists over the value of geriatric day hospitals in the rehabilitation of elderly patients , and cerebrovascular accident is a particularly common diagnosis among patients referred to these day hospitals . We carried out a prospect i ve , r and omized study to compare the outcomes of elderly stroke patients managed by a geriatric team using a day hospital facility versus conventional medical management . METHODS One hundred twenty elderly patients with acute stroke were r and omized to inpatient care on a stroke ward under the care of either a neurologist or a geriatric team . Those under the care of neurologists were hospitalized until the attending physician felt that the patients had reached full rehabilitation potential . Patients under the care of the geriatric team were discharged home as soon as the team felt they were able to cope and given follow-up rehabilitation at the day hospital . Family or community support was arranged when necessary for both treatment groups . On recruitment , patient demographics , medical history , clinical features related to stroke , and functional ability as measured by the Barthel Index were noted . Subjects were review ed at 3 and 6 months to assess functional level , hospital and outpatient services received , general well-being , mood , and level of satisfaction . Costs of treatment of the two groups were also compared . RESULTS Functional improvement ( Barthel Index score ) was greater in the group managed by the geriatricians with a day hospital facility compared with the conventional group at 3 months ( P = .03 ) . There were also fewer outpatient visits among the day hospital patients at 6 months ( P = .03 ) . No significant difference was found in costs between the two treatment groups . CONCLUSIONS Compared with conventional medical management , care in the geriatric day hospital hastened functional recovery and reduced outpatient visits in elderly stroke patients without additional cost The purpose of this intervention trial was to determine whether changes in bone mass distribution could be observed in postmenopausal women following hormone replacement therapy ( HRT ) and /or high-impact physical exercise . Eighty healthy women , aged 50 - 57 years , at < 5 years after the onset of menopause and with no previous use of HRT , were r and omly assigned to one of four groups : HRT ; exercise ( Ex ) ; HRT + Ex ( ExHRT ) ; and control ( Co ) . HRT administration was conducted in a double-blind manner for 1 year using estradiol plus noretisterone acetate ( Kliogest ) . The exercise groups participated in a 1 year progressive training program consisting of jumping and bounding activities . Subjects participated in two supervised sessions per week and were asked to perform a series of exercises at home 4 days/week . Bone measurements using a quantitative computed tomography scanner ( Somatom DR , Siemens ) were obtained from the proximal femur , midfemur , proximal tibia , and tibial shaft . Data were analyzed with a software program ( BONALYSE 1.3 ) calculating density ( g/cm(3 ) ) , cross-sectional area ( CSA ; mm(2 ) ) , and moments of inertia ( I(max ) , I(min ) , I(polar ) ) . In addition , the bone mass spectrum was determined as a function of the angular distribution around the bone mass center ( polar distribution ) and the distance from the bone mass center through the diaphyseal wall ( radial distribution ) . After the 1 year period , there was an overall interaction of group x time in bone mineral density ( BMD ) at the proximal femur ( p = 0.05 ) and tibial shaft ( p = 0.035 ) . Women in the ExHRT and HRT groups had increased proximal femur and tibial shaft BMD when compared with the change observed in the Co group ( p = 0.024 - 0.011 ) . The change was more pronounced in the cortical tibia , wherein the ExHRT group also differed from the Ex group ( p = 0.038 ) . No significant changes were found in bone CSA at any of the measured sites . The radial distribution indicated an increase of BMD in the endocortical part of the measured sites in the HRT and ExHRT groups and in the proximal tibia in the Ex group . The polar distribution showed that bone mass was redistributed in the anteroposterior direction . The changes in I(max ) , I(min ) , and I(polar ) in the HRT and ExHRT groups differed from those in the Co group at the proximal femur , midfemur , and proximal tibia ( p = 0.047 - 0.001 ) . The Ex group also differed from the Co group in I(max ) and I(polar ) at the proximal tibia ( p = 0.018 and 0.039 , respectively ) . These results support the idea that HRT acts primarily at the bone-marrow interface . The exercise intervention chosen for this study contributed to the maintenance of bone mass . Our results suggest that both HRT and exercise have local effects on bone mass . The change in bone mass distribution induced by HRT and exercise may play an important role in the alteration of bone strength We report here the design and baseline data from Project Active , a 2-yr r and omized trial design ed to compare the effectiveness of a Lifestyle physical activity intervention with the traditional Structured exercise prescription approach . Primary outcome measures are energy expenditure in physical activity ( estimated by kcal per kilogram of body weight of energy expenditure ) and cardiorespiratory fitness ( measured by maximal oxygen uptake ) . The participants , 235 initially sedentary and apparently healthy adults , were r and omized into either the Lifestyle or Structured intervention groups . The Lifestyle treatment consists of a personalized approach that accounts for an individual 's motivational readiness and preferences for integrating physical activity into daily routines . The Structured approach is the familiar exercise prescription that is based on a frequency , intensity , and duration formula . The primary hypothesis to be tested is that there will be a difference in physical activity and cardiorespiratory fitness measures between the two conditions at the end of 24 months . The secondary hypothesis is that both groups will make significant improvements from baseline in physical activity and cardiorespiratory fitness at the end of 6 months . Six months of active intervention are followed by 18 months of a tapered follow-up maintenance intervention in both groups . Primary outcome measures are measured after 6 and 24 months BACKGROUND The subjects were 26 healthy , sedentary adult females with the following characteristics : maximal oxygen consumption ( VO2max ) = 32.0 + /- 7.2 ml.kg-1.min-1 ; age = 32 + /- 5 yr ; body mass index ( BMI ) = 23.2 + /- 3.4 kg.m-2 who were r and omly assigned to control ( CON ; N = 8) ; treadmill training ( TM ; N = 8) ; or cycle ergometer training ( CY ; N = 10 ) to test the hypothesis that hematologic adaptations to endurance exercise training are specific to mode of exercise . METHODS Training , conducted 3 - 5 ( 3.4 + /- 0.06 ) d.week-1 at 80 % of mode specific VO2max for 12 weeks , was supervised and progressive , with estimated exercise energy expenditure equated across training groups . Plasma volume ( PV , T-1824 dilution ) ; calculated total blood ( THb ) and red cell volumes ( RCV ) ; calculated total hemoglobin ( THb ) and other hematologic variables were measured at baseline and weeks 2 , 4 , 8 and 12 of training . RESULTS Across 12 weeks of training , PV was decreased ( 95 % of baseline ) in the TM group but increased ( 106 % of baseline ) in the CY group ( p = 0.06 ) . Similar trends were observed for RCV ( p = 0.15 ) and TBV ( p = 0.08 ) . These results are in contrast to reported changes in PV , TBV and RCV in males following training . Hemodilution was observed in both training groups , reflected by decreases ( p < 0.05 ) in hematocrit ( Hct ) , hemoglobin ( Hb ) and RC count . Mean corpuscular Hb ( MCH ) and Hb content ( MCHC ) increased ( p < 0.05 ) with training . These changes , as well as trend toward increased ( p = 0.08 ) mean corpuscular volume ( MCV ) , suggested the probable presence of a RC population with a lower mean age and decreased oxyhemoglobin affinity . The possibility of Type II error can not be discounted in these trends , which suggest that PV , TBV and RCV may be affected by mode of endurance exercise in females BACKGROUND Previous research indicates that patients exiting a 12-week cardiac rehabilitation program ( CRP ) have difficulty maintaining an adequate exercise program . Thus , the authors ' purpose was to determine if a home-based exercise program would enable patients to maintain/improve their blood lipids , body composition , and functional capacity after exiting the CRP . METHODS Thirty-one patients exiting an initial 12-week CRP were assigned r and omly to the home-based ( HB ) intervention or the st and ard care ( SC ) condition . After one home visit , the HB participants ( n = 16 ) were contacted by telephone every other week by CRP staff and completed and returned weekly exercise logs . The SC participants ( n = 15 ) had no contact with the CRP other than to schedule follow-up tests . A third group ( n = 17 ) , r and omly selected from patients that elected to remain in the center-based CRP ( CB ) for the same duration , also were examined . All groups underwent exercise testing , fasting blood lipid analysis , and body composition assessment before starting CRP ( 0 M ) , after 3 months ( 3 M ) in a st and ard CRP , and after 9 months ( 12 M ) in either HB , SC , or CB condition ( 12 months after starting CRP ) . RESULTS Analysis of variance indicated that there were significant increases in metabolic equivalents and high-density lipoprotein , in all three groups , over time . However , analysis of covariance revealed no significant differences between the HB , SC , and CB groups at 12 M for any variable . CONCLUSIONS These data indicate that the HB program was as effective as the CB program at improving/maintaining functional capacity , blood lipids , and body weight/composition . The similar success of the SC group is likely due to their prior experience in CRP and knowledge of follow-up testing . Home-based maintenance program could be offered as a low-cost alternative to CB programs This study investigated changes in body composition , resting energy expenditure ( REE ) , appetite , and mood in 128 obese women who were r and omly assigned to 1 of 4 treatment conditions : diet alone , diet plus aerobic training , diet plus strength training , or diet combined with aerobic and strength training ( i.e. , combined training ) . All women received the same 48-week group behavioral program and were prescribed the same diet . Exercising participants were provided 3 supervised exercise sessions per week for the first 28 weeks and 2 sessions weekly thereafter . Participants across the 4 conditions achieved a mean weight loss of 16.5 + /- 6.8 kg at Week 24 , which decreased to 15.1 + /- 8.4 kg at Week 48 . There were no significant differences among conditions at any time in changes in weight or body composition . Women who received aerobic training displayed significantly smaller reductions in REE at Week 24 than did those who received strength training . There were no other significant differences among conditions at any time on this variable or in changes in appetite and mood Objectives To evaluate the long-term effects of regular moderate or vigorous intensity exercise on blood pressure and blood lipids in previously sedentary older women . Design Subjects were r and omly assigned to either a supervised centre-based ( CB ) or a minimally supervised home-based ( HB ) exercise program , initially for 6 months . Within each program , subjects were further r and omized to exercise either at moderate ( 40–55 % heart rate reserve , HRres ) or vigorous intensity ( 65–80 % HRres ) . After 6 months , all groups continued a HB moderate or vigorous exercise program for another 12 months . Methods Healthy , sedentary women ( aged 40–65 years ) ( n = 126 ) were recruited from the community . Subjects exercised three times per week for 30 min . They were evaluated at baseline , 6 , 12 and 18 months . Results There was a significant fall of 2.81 mmHg in systolic blood pressure ( P = 0.049 ) and 2.70 mmHg in diastolic blood pressure ( P = 0.004 ) after correction for age and baseline values with moderate exercise , but not with vigorous-intensity exercise . When this analysis was repeated with the change in body mass included , the results were unchanged . After correction for potential confounding factors , there was a significant fall in total cholesterol and low density lipoprotein cholesterol with vigorous but not moderate exercise at 6 months ( P < 0.05 ) but not at 18 months . Conclusions In this largely normotensive population of older women , a moderate , but not vigorous exercise program , achieved sustained falls in resting systolic and diastolic blood pressure over 18 months . The study demonstrates that , in older women , moderate intensity exercise is well accepted , sustainable long-term and has the health benefit of reduced blood pressure Different modalities of assisted ventilation improve breathlessness and exercise tolerance in patients with chronic obstructive pulmonary disease ( COPD ) . The aim of this study was to evaluate the effects of the addition of assisted ventilation during exercise training on the outcome of a structured pulmonary rehabilitation programme ( PRP ) in COPD patients . Thirty-three male patients with stable COPD ( mean ( SD ) forced expiratory volume in 1 s ( FEV1 ) 44 ( 16 ) % pred ) , without chronic ventilatory failure , undergoing a 6-week multidisciplinary outpatient PRP including exercise training , were r and omised to training during either mask proportional assist ventilation ( PAV : 18 patients ) or spontaneous breathing ( SB : 15 patients ) . Assessment included exercise tolerance , dyspnoea , leg fatigue , and health-related quality of life ( HRQL ) . Five out of 18 patients ( 28 % ) in the PAV group dropped out due to lack of compliance with the equipment . Both groups showed significant post-PRP improvements in exercise tolerance ( peak work rate difference : 20 ( 95 % Cl 2.4 - 37.6 ) and 14 ( 3.8 % CI to 24.2 ) W in PAV and SB group , respectively ) , dyspnoea and leg fatigue , but not in HRQL , without any significant difference between groups . It is concluded that with the modality and in the patients assessed in this study assisted ventilation during training sessions included in a multidisciplinary PRP was not well tolerated by all patients and gave no additional physiological benefit in comparison with exercise training alone Employing a r and omized controlled trial , this study documents the effects of six months of physical activity and six month follow-up on reduction in social physique anxiety ( SPA ) in older adults . In addition , the role played by changes in behavioral , physiological , and psychological predictors of changes in SPA were examined . Participants ( n = 174 , mean age = 65 yrs ) were r and omly assigned to one of two activity groups and engaged in a six-month structured exercise program . Measures of physique anxiety were taken at baseline , six and twelve months . Latent growth curve analyses revealed significant reductions in SPA over the course of the 12-month period . Structural analyses controlling for treatment condition indicated that improvements in self-efficacy and fitness were significant predictors of changes in SPA but that changes in body fat and exercise frequency did not contribute to variation in SPA . Overall this model accounted for 19 % of the variation in SPA changes . The extent to which changes in SPA may contribute to continued physical activity participation in older adults and how exercise programs might effectively influence predictors of SPA are discussed BACKGROUND Older adults who receive training for functional skills in context ually appropriate environments may show greater functional improvement than persons trained in a traditional environment . Functionally limited older adults receiving training in context ually appropriate environments ( simulated home and community setting s ) may show greater improvement in activities of daily living ( ADL ) than persons trained in a traditional manner . METHODS Eighty-eight patients from a day hospital , aged 65 years or older , were r and omized to either receive rehabilitation in a simulated environment ( Easy Street ) or in a gymnasium setting . Rehabilitation focused on retraining functional skills in a context ually appropriate environment ( Easy Street ) or in a traditional setting ( gymnasium ) using motor learning principles for a period of 16 weeks . Outcome measures included the Structured Assessment of Instrumental Living Skills ( SAILS ) , a performance measure with criterion and timed components ; a self-report health status question naire , the Short Form-36 ( SF-36 ) ; and the patient-orientated goal -directed Canadian Occupational Performance Measure ( COPM ) . RESULTS There were no group differences on any of the outcome measures : SAILS ( p = .3 ) ; the SF-36 physical ( p = .83 ) and mental ( p = .51 ) ; and the COPM performance scale ( p = .94 ) and satisfaction scale ( p = .40 ) . CONCLUSIONS Although we have not excluded benefits of context ually appropriate rehabilitation environments with different intervention approaches , at different stages of rehabilitation or with patients at higher functional levels , our results suggest the appropriateness of a moratorium on these expensive interventions pending demonstration of clear positive effects determined from further study OBJECTIVES This study sought to determine whether a moderate intensity supervised exercise training program , performed immediately after an uncomplicated acute myocardial infa rct ion , improves recovery in cardiac autonomic function compared with st and ard advice about activity at home . BACKGROUND Exercise training has beneficial effects on cardiac autonomic function and may improve prognosis after acute myocardial infa rct ion . METHODS Thirty-nine male and 10 female patients , mean ( + /-SE ) age 57 + /- 1 years , with an uncomplicated acute myocardial infa rct ion were r and omized to either a 6-week moderate intensity supervised hospital-based exercise training program ( exercise group ) or to an unsupervised low intensity home walking program ( control group ) . Outcome measures included changes in baroreflex sensitivity ( phenylephrine bolus method ) and heart rate variability ( 24-h Holter monitoring ) and the endurance time at 85 % of peak oxygen consumption . RESULTS At baseline , there were no significant differences in left ventricular ejection fraction ( 57 + /- 2 % vs. 53 + /- 2 % ) , frequency of anterior infa rct ion ( 27 % vs. 18 % ) and peak creatine kinase ( 1,256 + /- 170 vs. 2,599 + /- 295 IU ) between the exercise and control groups . Baroreflex sensitivity ( 10.5 + /- 1.0 vs. 8.4 + /- 1.2 ms/mm Hg ) and time domain measures of heart rate variability were also similar . After completion of the program , the exercise group exercised for a median of 15 min ( interquartile range 12 to 25 ) at a workload of 104 + /- 7 W compared with 7 min ( interquartile range 3.5 to 12 ) at a workload of 89 + /- 8 W in the control group ( p < 0.01 ) . There were significant ( p < 0.001 ) improvements in baroreflex sensitivity and heart rate variability for the 49 patients combined but no differences between the exercise and control groups . Baroreflex sensitivity improved by 3.4 + /- 1.0 and 1.7 + /- 1.0 ms/mm Hg and the st and ard deviation of 24-h RR intervals by 36 + /- 6 and 40 + /- 10 ms , respectively ( p > 0.1 ) . CONCLUSIONS A hospital-based exercise training program increased endurance capacity but did not improve recovery of cardiovascular antonomic function after uncomplicated acute myocardial infa rct ion OBJECTIVE The goal of this study was to compare the effectiveness of home-based , transtelephonically monitored cardiac rehabilitation with st and ard , on-site , supervised cardiac rehabilitation . BACKGROUND Participation in cardiac rehabilitation has been demonstrated to increase exercise capacity , decrease cardiovascular symptoms , improve psychosocial status , and decrease total and cardiovascular mortality rates in patients with coronary heart disease . Because of multiple factors , national overall participation is only at 15 % of eligible patients . METHODS Effects of a 3-month home-based , transtelephonically monitored rehabilitation program ( n = 83 patients ) with simultaneous voice and electrocardiographic transmission to a central ly located nurse coordinator were compared with effects of a st and ard on-site rehabilitation program ( n = 50 patients ) . The study design was a multicenter , controlled trial . Primary outcome variables were peak aerobic capacity and quality of life , as measured by the Health Status Question naire . RESULTS Patients in the home-based monitoring program increased peak aerobic capacity to a similar degree as patients who exercised on site ( 18 % vs 23 % ) . Quality of life domains of physical functioning , social functioning , physical role limitations , emotional role limitations , bodily pain , and energy/fatigue improved similarly in both groups . There were no circulatory arrests or other major exercise-related medical events in either group . A total of 3100 hours of home exercise were transtelephonically monitored . CONCLUSIONS Patients with coronary heart disease can effectively participate in home-based , monitored cardiac rehabilitation , with exercise and quality of life improvements comparable to those demonstrated at on-site programs BACKGROUND Although exercise parameters such as intensity and format have been shown to influence exercise participation rates and physiological outcomes in the short term , few data are available evaluating their longer-term effects . The study objective was to determine the 2-year effects of differing intensities and formats of endurance exercise on exercise participation rates , fitness , and plasma HDL cholesterol levels among healthy older adults . METHODS AND RESULTS Higher-intensity , group-based exercise training ; higher-intensity , home-based exercise ; and lower-intensity , home-based exercise were compared in a 2-year r and omized trial . Participants were 149 men and 120 postmenopausal women 50 to 65 years of age who were sedentary and free of cardiovascular disease . Recruitment was achieved through a r and om digit-dial community telephone survey and media promotion . All exercise occurred in community setting s. For higher-intensity exercise training , three 40-minute endurance training sessions per week were prescribed at 73 % to 88 % of peak treadmill heart rate . For lower-intensity exercise , five 30-minute endurance training sessions per week were prescribed at 60 % to 73 % of peak treadmill heart rate . Treadmill exercise performance , lipoprotein levels and other heart disease risk factors , and exercise adherence were evaluated at baseline and across the 2-year period . Treadmill exercise test performance improved for all three training conditions during year 1 and was successfully maintained during year 2 , particularly for subjects in the higher-intensity , home-based condition . Subjects in that condition also showed the greatest year 2 exercise adherence rates ( P < .003 ) . Although no significant increases in HDL cholesterol were observed during year 1 , by the end of year 2 subjects in the two home-based training conditions showed small but significant HDL cholesterol increases over baseline ( P < .01 ) . The increases were particularly pronounced for subjects in the lower-intensity condition , whose exercise prescription required more frequent exercise sessions per week . For all exercise conditions , increases in HDL cholesterol were associated with decreases in waist-to-hip ratio in both men and women ( P < .04 ) . CONCLUSIONS While older adults can benefit from initiating a regular regimen of moderate-intensity exercise in terms of improved fitness levels and small improvements in HDL cholesterol levels , the time frame needed to achieve HDL cholesterol change ( 2 years ) may be longer than that reported previously for younger population s. Frequency of participation may be particularly important for achieving such changes . Supervised home-based exercise regimens represent a safe , attractive alternative for achieving sustained participation Background : Falls are a major cause of morbidity in old age . A small number of fall prevention trials in cognitively intact community-dwelling older people have been effective . This study set out to examine the preventability of falls in older people living in institutional care . Objective : To evaluate the effectiveness of falls risk factor assessment /modification and seated balance exercise training in reducing falls among elderly people living in residential care . Methods : 133 residents with a mean age of 84± ( SD ) 6.8 years were allocated at r and om by home to receive either a 6-month falls risk factor assessment /modification and seated balance exercise training programme ( n = 77 ) or 6 months of reminiscence therapy ( n = 56 ) . The risk factors targeted were postural hypotension , polypharmacy , visual acuity , and ambient lighting levels . Falls risk factor assessment s and recommendation for modifications were performed at baseline in the intervention group and assessment s repeated at 6 months . Functional reach , reaction time , timed up- and - go , grip strength , spinal flexibility , and Philadelphia Geriatric Centre Morale Scale and Mini-Mental State Examination scores were determined at baseline and at 6 months by a ‘ blind ’ observer . Falls and fractures were then monitored in both groups during a 7- to 12-month falls-monitoring follow-up period . Results : Only 90 of 133 ( 67.7 % ) residents completed the 6-month intervention period , and 84 ( 63.2 % ) completed the 7- to 12-month falls-monitoring follow-up period . Both prevalence of postural hypotension ( p = 0.0005 ) and poor visual acuity ( p = 0.04 ) were reduced in the intervention group . There was no difference between the groups in the number of falls sustained , the risk of falling [ odds ratio 0.45 ( 95 % CI 0.19–1.14 ) ] , or in the risk of recurrent falling [ odds ratio 1.07 ( 95 % CI 0.40–2.97 ) ] . No significant differences were found between the groups with regard to change in other outcome measures . Conclusions : The high drop-out rate reduced the power of this study to detect any effect of the interventions used . It is possible that either the exercises were not sufficiently vigorous or that to improve balance exercises must be performed st and ing . Further research is required to identify effective fall prevention strategies for elderly people in residential setting Hydrotherapy for OA of the hip has rarely been evaluated in controlled studies . Forty-seven patients with OA of the hip were followed for 18 weeks . Patients were r and omly allocated either to a regimen of home exercises or to twice weekly hydrotherapy for 6 weeks in addition to home exercises . There was an improvement seen in both subjective and objective measures in both groups with treatment . There was no significant difference between the two groups . Response to treatment appeared independent of age , sex and radiological severity . We conclude that for most patients , a carefully grade d and supervised regimen of home exercises is beneficial and there is little benefit in adding hydrotherapy to this regimen OBJECTIVE To examine the effects of a 3-month low-intensity exercise program on physical frailty . DESIGN R and omized clinical trial . SETTING Regional tertiary-care hospital and academic medical center with an outpatient rehabilitation fitness center . PARTICIPANTS Eighty-four physically frail older adults ( mean age , 83 + /- 4 yrs ) . INTERVENTION Three-month low-intensity supervised exercise ( n = 48 ) versus unsupervised home-based flexibility activities ( n = 36 ) . MAIN OUTCOME MEASURES Physical performance test , measures of balance , strength , flexibility , coordination , speed of reaction , peripheral sensation . RESULTS Significant improvement was made by the exercise group on our primary indicator of frailty , a physical performance test ( PPT ) ( 29 + /- 4 vs 31 + /- 4 out of a possible 36 points ) , as well as many of the risk factors previously identified as contributors to frailty ; eg , reductions in flexibility , strength , gait speed , and poor balance . Although the home exercise control group showed increases in range of motion , the improvements in flexibility did not translate into improvements in physical performance capacity as assessed by the PPT . CONCLUSIONS Our results suggest that physical frailty is modifiable with a program of modest activities that can be performed by virtually all older adults . They also indicate that exercise programs consisting primarily of flexibility activities are not likely to reverse or attenuate physical frailty . Although results suggest that frailty is modifiable , it is not likely to be eliminated with exercise , and efforts should be directed toward preventing the condition PURPOSE This r and omized controlled study assessed whether adding a program of high-intensity strength training ( 80 % of maximum ) to an outpatient cardiac rehabilitation program would be a safe and effective means of improving muscle strength and body composition . METHODS Thirty-eight cardiac patient volunteers ( 29 men and 9 women ) were r and omized to either high-intensity strength training or flexibility training added concurrently to a 12-week outpatient cardiac rehabilitation aerobic exercise program . Muscle strength , local muscle endurance , joint flexibility , maximum treadmill tolerance time , and body composition were measured before and after completion of the training . RESULTS The strength-trained patients ( n = 18 ) had greater increases in mean strength ( 90 + /- 19 % versus 9 + /- 4 % , P < 0.0001 ) and local muscle endurance ( 20 versus 6 times , P < 0.0001 ) , and decreases in mean perceived exertion for lifting the initial one repetition maximum load ( 11 + /- 1 versus 15 + /- 1 , P < 0.0001 ) when compared with flexibility-trained patients ( n = 16 ) . The strength group lost more body fat ( 2.8 + /- 2.0 versus 1.3 + /- 2.0 kg , P < 0.01 ) , tended to gain more lean tissue ( 1.5 + /- 2.3 versus 0.5 + /- 1.2 kg , P < 0.10 ) , and had greater improvements in treadmill time ( 2.3 + /- 1.3 versus 1.2 + /- 1.0 minute , P < 0.02 ) than did the flexibility group . Improvements in joint flexibility were similar for each group . None of the subjects had evidence of cardiac ischemia or arrhythmia during the training sessions . CONCLUSIONS Medically supervised high-intensity strength training is well tolerated when added to the aerobic training of cardiac rehabilitation programs and allows patients to aggressively gain the strength and endurance they will need to complete daily living tasks at lower perceived efforts . Strength training also reduces cardiac risk factors by improving body composition and maximum treadmill exercise time OBJECTIVE --To determine the effectiveness of group- vs home-based exercise training of higher and lower intensities among healthy , sedentary older adults . DESIGN --Year-long r and omized , controlled trial comparing ( 1 ) higher-intensity group-based exercise training ; ( 2 ) higher-intensity home-based exercise training ; ( 3 ) lower-intensity home-based exercise training ; or ( 4 ) assessment -only control . SETTING --General community located in northern California . PARTICIPANTS --One hundred sixty women and 197 men 50 to 65 years of age who were sedentary and free of cardiovascular disease . One out of nine persons contacted through a community r and om-digit-dial telephone survey and citywide promotion were r and omized . INTERVENTIONS --For higher-intensity exercise training , three 40-minute endurance training sessions per week were prescribed at 73 % to 88 % of peak treadmill heart rate . For lower-intensity exercise training , five 30-minute endurance training sessions per week were prescribed at 60 % to 73 % of peak treadmill heart rate . MAIN OUTCOME MEASURES --Treadmill exercise test performance , exercise participation rates , and heart disease risk factors . RESULTS --Compared with controls , subjects in all three exercise training conditions showed significant improvements in treadmill exercise test performance at 6 and 12 months ( P less than .03 ) . Lower-intensity exercise training achieved changes comparable with those of higher-intensity exercise training . Twelve-month exercise adherence rates were better for the two home-based exercise training conditions relative to the group-based exercise training condition ( P less than .0005 ) . There were no significant training-induced changes in lipid levels , weight , or blood pressure . CONCLUSIONS --We conclude that ( 1 ) this community-based exercise training program improved fitness but not heart disease risk factors among sedentary , healthy older adults ; ( 2 ) home-based exercise was as effective as group exercise in producing these changes ; ( 3 ) lower-intensity exercise training was as effective as higher-intensity exercise training in the home setting ; and ( 4 ) the exercise programs were relatively safe OBJECTIVE To assess the long term effects of weight loss with and without additional aerobic and weight training exercises on exercise tolerance and cardiorespiratory fitness in obese women . EXPERIMENTAL DESIGN R and omized prospect i ve study for an approximately one-year community setting . PATIENTS 31 healthy obese women volunteers ( age 42.8 yrs + /- 6 SD ) recruited by community advertisement . INTERVENTION All subjects underwent a weight loss program consisting of low calorie diet and behavior therapy for a minimum of 46 weeks . They were r and omly assigned to one of the four groups . Group A : diet alone , Group B : diet plus aerobic exercise program in a supervised group setting , Group C : Diet plus weight training and Group D : diet plus weight training plus aerobic exercise program . MEASURES Exercise time ( Tex ) peak sustained workload ( Wp ) , peak oxygen consumption ( VO2 ) , oxygen pulse and the rate of change of VO2 on recovery ( VO2rec ) were measured at the beginning and after 47.5 weeks + /- 1.5 SD , of the program . RESULTS All subjects lost weight and achieved increased Tex and lowered resting VO2 . VO2 peak and VO2 peak kg-1 increase in Groups B and D only . O2 pulse and VO2rec improved in group D. Improvements in exercise time correlated significantly with initial exercise time and weight loss . CONCLUSIONS Weight loss increase Tex irrespective of participation in an exercise program . However , evidence of improved aerobic fitness occurred only in groups performing aerobic exercise PURPOSE The convalescent period after myocardial infa rct ion ( MI ) has been associated with a " spontaneous " improvement in functional aerobic capacity that may be because of normal recovery processes unrelated to formal exercise training . The purpose of this study was to determine whether the frequency of formal training sessions is an important variable affecting the magnitude of improvement in cardiorespiratory fitness during phase II cardiac rehabilitation . METHODS The effect of exercise training frequency on cardiorespiratory fitness was evaluated during a 5-week early ( phase II ) cardiac rehabilitation program in 50 low-risk , male patients recovering from acute MI . Baseline grade d treadmill tests to fatigue endpoints , with direct measurement of maximal oxygen uptake ( VO2max ) , were administered 4 weeks after MI . The subjects were then r and omly assigned to either a control group ( n = 12 ) and restricted to " very light " physical activity ( requiring < 50 % of VO2max ) at home , or to one of three training groups which , in addition to very light home activity , performed moderately intense ( approximately 70 % of VO2max ) aerobic exercise for 30 to 35 minutes either once per week ( n = 13 ) , twice per week ( n = 13 ) , or three times per week ( n = 12 ) in the hospital-based phase II program . The four groups were similar in age , clinical status , and use of beta- and calcium channel blockers . RESULTS Submaximal and maximal cardiorespiratory responses were initially similar in all four groups . Each of the four groups demonstrated significant ( P < .05 ) increases in maximal treadmill duration at follow-up . However , VO2max increased significantly only in the three training groups . The spontaneous improvement in treadmill duration in the control group , in the absence of formal exercise training , may simply reflect recovery from the acute cardiac event . Those training two and three sessions per week also showed significant , comparable decreases in submaximal exercise heart rate and rate-pressure product and similar increases in maximal treadmill duration and VO2max . CONCLUSIONS Results suggest that two exercise sessions per week is as effective as three per week for cardiorespiratory conditioning in the early weeks of phase II cardiac rehabilitation Progressive resistance training has positive effects on the health of elderly people , however exercise programs for seniors frequently focus on other forms of exercise . This study is a r and omised trial with a blinded assessor comparing a community based progressive resistance training program ( n = 20 ) with a flexibility program ( n = 20 ) , both one hour twice weekly for 10 weeks . Outcomes were strength , gait , balance and quality of life . Progressive resistance training had a greater effect than flexibility training on right sided quadriceps strength ( mean difference between groups = 7.7 % ; 95 % CI 3.6 - 11.8 % , p < 0.003 MANOVA ) , left sided quadriceps strength ( mean difference = 9.9 % ; 95 % CI 5.6 - 14.2 % , p < 0.003 MANOVA ) , left sided biceps strength ( mean difference = 15.2 % ; 95 % CI 11.7 - 19.2 % , p < 0.003 MANOVA ) , functional reach ( mean difference = 11.7 % ; 95 % CI 7.1 - 16.3 % , p < 0.003 MANOVA ) and step test ( mean difference = 8.6 % ; 95 % CI 3.8 - 13.4 % , p < 0.003 MANOVA ) . Neither group had improvements in SF36 quality of life measures . Results suggest progressive resistance training produces greater strength , gait and balance improvements in elderly people than a flexibility exercise program Study Design . R and omized clinical trial . Objectives . To compare the effects of spinal manipulation combined with low-tech rehabilitative exercise , MedX rehabilitative exercise , or spinal manipulation alone in patient self-reported outcomes over a two-year follow-up period . Summary of Background Data . There have been few r and omized clinical trials of spinal manipulation and rehabilitative exercise for patients with neck pain , and most have only reported short-term outcomes . Methods . One hundred ninety-one patients with chronic neck pain were r and omized to 11 weeks of one of the three treatments . Patient self-report question naires measuring pain , disability , general health status , improvement , satisfaction , and OTC medication use were collected after 5 and 11 weeks of treatment and 3 , 6 , 12 , and 24 months after treatment . Data were analyzed taking into account all time points using repeated measures analyses . Results . Ninety-three percent ( 178 ) of r and omized patients completed the 11-week intervention phase , and 76 % ( 145 ) provided data at all evaluation time points over the two-year follow-up period . A difference in patient-rated pain with no group-time interaction was observed in favor of the two exercise groups [ F(2141 ) = 3.2;P = 0.04 ] . There was also a group difference in satisfaction with care [ F(2143 ) = 7.7;P = 0.001 ] , with spinal manipulation combined with low-tech rehabilitative exercise superior to MedX rehabilitative exercise ( P = 0.02 ) and spinal manipulation alone ( P < 0.001 ) . No significant group differences were found for neck disability , general health status , improvement , and OTC medication use , although the trend over time was in favor of the two exercise groups . Conclusion . The results of this study demonstrate an advantage of spinal manipulation combined with low-tech rehabilitative exercise and MedX rehabilitative exercise versus spinal manipulation alone over two years and are similar in magnitude to those observed after one-year follow-up . These results suggest that treatments including supervised rehabilitative exercise should be considered for chronic neck pain sufferers . Further studies are needed to examine the cost effectiveness of these therapies and how spinal manipulation compares to no treatment or minimal intervention This investigation examined predictors of compliance with exercise therapy in a clinical trial involving older adults with knee osteoarthritis ( OA ) . The study sample was partitioned into tertiles by level of compliance to determine its effect on several clinical outcome measures in the trial ( i.e. , knee pain , difficulty with activities of daily living , and performance-related disability ) . The participants ( N = 439 ) first completed all baseline assessment s and were then r and omly assigned to one of three treatment conditions : health education control , aerobic exercise , or resistance exercise . The two exercise treatments involved a 3-month center-based phase and a 15-month home-based phase . Variables in five categories ( i.e. , demographic , fitness , health-related quality of life , performance-related disability , and prior exercise behavior ) were entered as predictors of attendance and time spent exercising during each session for three different periods of time across the course of the study . Results of these analyses revealed that it was possible to explain more variance for time spent exercising ( approximately 40 % ) during the first 3 months than for attendance ( approximately 10 % ) . Furthermore , once participants completed the first 3 months of their training , prior behavior was the strongest predictor of exercise compliance . In most cases , the regression models accounted anywhere from 26 to 46 % of the variance in attendance or time spent exercising ( 7 of the 8 P values < 0.01 ) . In general , demographic , fitness , psychosocial , and disability-related measures did not predict compliance with any consistency across the various phases of the trial . Analysis of the dose-response data suggest that , in the use of aerobic exercise to deter disability in older people with knee OA , consideration should be given to prescribing frequent bouts of activity ( at least 3 times each week ) of moderate duration ( approximately 35 min ) |
790 | 29,284,913 | Results : The findings revealed that telemental health care is an extended domain supportive of conventional mental health services .
Currently , telemental health care has multiple capabilities and technologies for providing effective interventions to patients with various mental illnesses .
It provides clinicians with a wide variety of innovative choices and strategies for mental interventions , in addition to significant future potentials .
Conclusions : Telemental health care can provide effective and adaptable solutions to the care of mental illnesses universally .
While being comparable to in-person services , telemental health care is particularly advantageous and inexpensive through the use of current technologies and adaptable design s , especially in isolated communities | Background and Objectives : Due to the high costs of conventional mental health care , there has been a rise in the application of web-based technologies in recent years , i.e. , telemental health care . | BACKGROUND Increasing access to psychotherapy for posttraumatic stress disorder ( PTSD ) is a primary focus of the Department of Veterans Affairs ( VA ) healthcare system . Delivery of treatment via video telehealth can exp and availability of treatment and be equally effective as in-person treatment . Despite VA efforts , barriers to establishing telehealth services remain , including both provider acceptance and organizational obstacles . Thus , development of specific strategies is needed to implement video telehealth services in complex healthcare systems , like the VA . MATERIAL S AND METHODS This project was guided by the Promoting Action on Research Implementation in Health Services framework and used external facilitation to increase access to psychotherapy via video telehealth . The project was conducted at five VA Medical Centers and their associated community clinics across six states in the South Central United States . RESULTS Over a 21-month period , 27 video telehealth clinics were established to provide greater access to evidence -based psychotherapies for PTSD . Examination of change scores showed that participating sites averaged a 3.2-fold increase in unique patients and a 6.5-fold increase in psychotherapy sessions via video telehealth for PTSD . Differences between participating and nonparticipating sites in both unique patients and encounters were significant ( p=0.041 and p=0.009 , respectively ) . Two groups emerged , separated by degree of engagement in the facilitation intervention . Facilitation was perceived as useful by providers . CONCLUSIONS To our knowledge , this is the first prospect i ve study of external facilitation as an implementation strategy for telehealth . Our findings suggest that external facilitation is an effective and acceptable strategy to support providers as they establish clinics and make complex practice changes , such as implementing video telehealth to deliver psychotherapy Store- and -forward telepsychiatry , or asynchronous telepsychiatry ( ATP ) , which allows clinical data , including video to be collected to be review ed at a later time by a specialist , has been described as a feasible alternative to real-time telepsychiatry , or synchronous telepsychiatry ( STP ) , as a consultation model for primary care . In theory , ATP should be economically more cost-effective than STP due to the increased flexibility of patient data collection and the substitution of the time of specialists with that of lower-cost providers . The aim of this study was to conduct a retrospective cost- analysis comparing ATP with STP and traditional in-person psychiatric consultations in the primary care setting . One hundred and twenty five ATP consultations were performed and fixed and marginal costs were calculated for each model using inputs such as equipment costs , time spent by providers and support staff , and hourly salaries . The fixed costs were $ 7,000 and $ 20,000 for ATP and STP and marginal costs were $ 68.18 , $ 107.50 , and $ 96.36 , respectively , for the three groups . STP was the most expensive of the three types of consultations . ATP became the most cost-effective of the three models beyond 249 consultations . The marginal cost savings of ATP were due to substitution of low-cost providers for specialists . ATP represents a potential disruptive healthcare process that could allow more affordable care to be delivered to a larger population of patients . A full accounting of ATP 's efficiency will require further studies , including prospect i ve cost-benefit analyses from the perspectives of the patient , provider , and society The provision of mental health services via videoconferencing tele-mental health has become an increasingly routine component of mental health service delivery throughout the world . Emphasizing the research literature since 2003 , we examine : 1 ) the extent to which the field of tele-mental health has advanced the research agenda previously suggested ; and 2 ) implication s for tele-mental health care delivery for special clinical population s. Previous findings have demonstrated that tele-mental health services are satisfactory to patients , improve outcomes , and are probably cost effective . In the very small number of r and omized controlled studies that have been conducted to date , tele-mental health has demonstrated equivalent efficacy compared to face-to-face care in a variety of clinical setting s and with specific patient population s. However , method ologically flawed or limited research studies are the norm , and thus the research agenda for tele-mental health has not been fully maximized . Implication s for future research and practice are discussed Background : We conducted a r and omised study to investigate whether providing a self-guided Internet support group to cancer patients affected mood disturbance and adjustment to cancer . Methods : Baseline and 1- , 6- and 12-month assessment s were conducted from 2004 to 2006 at a national rehabilitation centre in Denmark . A total of 58 rehabilitation course weeks including 921 survivors of various cancers were r and omly assigned to a control or an intervention group by cluster r and omisation . The intervention was a lecture on the use of the Internet for support and information followed by participation in an Internet support group . Outcome measures included self-reported mood disturbance , adjustment to cancer and self-rated health . Differences in scores were compared between the control group and the intervention group . Results : The effect of the intervention on mood disturbance and adjustment to cancer showed a transient difference at the 6-month follow-up , where the intervention group reported less reduction in anxious preoccupation ( P=0.04 ) , helplessness ( P=0.002 ) , confusion ( P=0.001 ) and depression ( P=0.04 ) . Otherwise no significant effects were observed . Conclusion : We conclude that use of Internet-based support groups in cancer patients still needs to confirm long-lasting psychological effects BACKGROUND This study investigated the efficacy of an Internet-based self-help program with minimal therapist contact via e-mail for Swedish university students with social phobia and public speaking fears . The main objective was to test if the Internet-based self-help program would be more effective if five live group exposure sessions were added . METHODS Thirty-eight students meeting the diagnostic and statistical manual of mental disorders , 4th edition criteria for social phobia were r and omized into two different treatment groups : Internet delivered cognitive behavior therapy combined with five group exposure sessions ( ICBT+ exp ) or the Internet program alone ( ICBT ) . RESULTS Results were analyzed on an intention-to-treat basis . Both treatment groups showed significant improvement from pre- to post-test , and from pre-test to 1-year follow-up , on all measured dimensions ( social anxiety , general anxiety , depression levels , and quality of life ) . For both the groups , the average within-group effect sizes for the primary social anxiety scales , expressed as Cohen 's d , were comparable to those seen in traditionally administered cognitive behavioral therapy both at post-test and at 1- year follow-up . CONCLUSIONS The results suggest that the Internet-based self-help program on its own is efficient in the treatment of university students with social phobia . Adding group exposure sessions did not improve the outcome significantly Trends over the past decade have shown that online counseling has grown in terms of popularity among consumers and clinicians alike ; however , little , if any empirical evidence exists that examines client attitudes towards online counseling as alternative to traditional face-to-face therapy . Therefore , this study investigated client attitudes towards online counseling . Data was collected from 48 e-clients who received online counseling at the Center for Online Addiction . Variables such as client perceptions and concerns about using online counseling , clients ' reasons for seeking online counseling over in-office treatment , and demographic profiles of e-clients were assessed . Results suggested that Caucasian , middle-aged males , with at least a four-year bachelors degree were most likely to use online counseling and anonymity , convenience , and counselor credentials were the most cited reasons they sought online counseling over in-office treatment . The lack of perceived privacy and security during online chat sessions and the fear of being caught while conducting online sessions were the main concerns reported by e-clients . A better underst and ing of client motives and perceptions towards online counseling helps to guide treatment in using the Internet as a clinical tool , especially as the Internet becomes increasingly more available in previously remote markets and the field of online counseling continues to grow This method ological article provides a description of the design , methods , and rationale of the first prospect i ve , noninferiority design ed r and omized clinical trial evaluating the clinical and cost implication s of delivering an evidence -based cognitive-behavioral group intervention specifically treating posttraumatic stress disorder ( PTSD ) with a trauma-focused intervention via video teleconferencing ( VTC ) . PTSD is a prevalent mental health problem found among returning Operation Iraqi Freedom/Operation Enduring Freedom ( OIF/OEF ) military population s. These returning military personnel often live in rural areas and therefore have limited access to care and specialized psychological treatments . In the field of mental health , telemental health ( TMH ) technology has introduced a potential solution to the persistent problem of access to care in remote areas . This study is enrolling approximately 126 returning veterans with current combat-related PTSD who are receiving services through the Veteran Administration ( VA ) mental health care clinics on 4 Hawaiian Isl and s. Cognitive Processing Therapy ( CPT ) , an empirically supported manualized treatment for PTSD , is being delivered across 9 cohorts . Participants are assigned to either the experimental VTC condition or the in-person control condition . Assessment s measuring clinical , process , and cost outcomes are being conducted at baseline , mid-treatment , post-treatment , and 3 and 6 months post-treatment . The study employs a noninferiority design to determine if the group treatment delivered via VTC is as good as the traditional in-person modality . In addition , a cost analysis will be performed in order to compare the cost of the 2 modalities . Novel aspects of this trial and specific challenges are discussed |
791 | 30,337,578 | Unintentional weight loss had a significant impact on all-cause mortality .
We found no protective effect of being overweight or obese for unintentional weight loss and MACE | The obesity paradox has been described in several observational cohorts and meta- analysis .
However , evidence of the intentionality of weight loss in all-cause deaths and major cardiovascular events ( MACE ) in prospect i ve cohorts is unclear .
We analysed whether involuntary weight loss is associated with increased cardiovascular events and mortality . | BACKGROUND The " obesity paradox " is defined as an inverse association of good health , survival and obesity . Usually in healthy persons the more obese you are the more metabolic complications you have ; however , thin patients with chronic obstructive pulmonary disease ( COPD ) have more cardiovascular complications and a higher mortality rate . OBJECTIVES To explore whether atherosclerosis and peripheral artery disease ( PAD ) contribute to the higher morbidity and mortality of patients with COPD . METHODS This prospect i ve study included 87 patients with chronic COPD who were treated in the pulmonary outpatient clinic ; all signed a consent form before enrollment . We documented their lung function ( FEV1 % ) , body mass index ( BMI ) and ankle brachial index ( ABI ) . The primary endpoints were to find an association between atherosclerosis and BMI in patients with COPD , and between atherosclerosis and severity of lung disease . RESULTS Average ABI was 1.01 + /- 0.20 , BMI was 29.33 + /- 7.48 kg/m2 , and the abdominal circumference was 107.34 + /- 18.87 cm . A positive correlation was found between BMI and ABI ( P=0.001 ) and between abdominal circumference and ABI ( P=0.000 ) . Patients with peripheral artery disease were older ( 73.6 + /- 11.5 vs. 68.1 + /- 11.6 years old , P= 0.04 ) , were thinner ( average BMI 25.5 + /- 6.2 vs. 31.06 + /- 7.3 , P= 0.001 ) , and had a lower abdominal circumference ( 97.7 + /- 18.3 vs. 111.7 + /- 17.5 cm , P=0.001 ) . No such difference was observed for years of smoking . Male PAD patients with COPD had a lower BMI ( 25.2 + /- 5.6 vs. 29.9 + /- 7.4 , P = 0.016 ) , and their abdominal circumference was smaller ( 96.1 + /- 18.0 vs. 110.2 + /- 16.5 cm , P=0.004 ) . Female PAD patients with COPD had a lower BMI ( 26.3 + /- 8.2 vs. 33.1 + /- 7.0 , P=0.045 ) , but their abdominal circumference was not different from females without PAD ( 102.0 + /- 19.7 vs. 114.0 + /- 19.4 cm , P=0.162 ) . Patients with PAD had a worse lung disease ( FEV1 % 34 + /- 8 % vs. 45 + /- 16 % , P=0.01 ) . During the 1 year of follow-up five patients died : two PAD patients due to acute myocardial infa rct ion and three non-PAD patients died from pulmonary insufficiency ( two patients ) and pulmonary emboli ( one patient ) . DISCUSSION We found that COPD patients with PAD were older and thinner and had a lower abdominal circumference and a more progressive lung disease . Extensive atherosclerosis in patients with COPD may partly explain the " obesity paradox " observed in patients with COPD Background The association between change in weight or body mass index , and mortality is widely reported , however , both measures fail to account for fat distribution . Change in waist circumference , a measure of central adiposity , in relation to mortality has not been studied extensively . Methods We investigated the association between mortality and changes in directly measured waist circumference , hips circumference and weight from baseline ( 1990–1994 ) to wave 2 ( 2003–2007 ) in a prospect i ve cohort study of people aged 40–69 years at baseline . Cox regression , with age as the time metric and follow-up starting at wave 2 , adjusted for confounding variables , was used to estimate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for change in body size in relation to mortality from all causes , cardiovascular disease and cancer . Results There were 1465 deaths ( 109 cancer , 242 cardiovascular disease ) identified during an average 7.7 years of follow-up from 21 298 participants . Compared to minimal increase in body size , loss of waist circumference ( HR : 1.26 ; 95 % CI : 1.09–1.47 ) , weight ( 1.80 ; 1.54–2.11 ) , or hips circumference ( 1.35 ; 1.15–1.57 ) were associated with an increased risk of all-cause mortality , particularly for older adults . Weight loss was associated with cardiovascular disease mortality ( 2.40 ; 1.57–3.65 ) but change in body size was not associated with obesity-related cancer mortality . Conclusion This study confirms the association between weight loss and increased mortality from all-causes for older adults . Based on evidence from observational cohort studies , weight stability may be the recommended option for most adults , especially older adults Conflicting results have been reported concerning the association between body weight and longevity . The shape of the curve relating weight to all-cause mortality has been variously described as linear , J-shaped , and even U-shaped . To assess the validity of the evidence for optimal weight recommendations , we examined the 25 major prospect i ve studies on the subject . Each study had at least one of three major biases : failure to control for cigarette smoking , inappropriate control of biologic effects of obesity , such as hypertension and hyperglycemia , and failure to control for weight loss due to sub clinical disease . The presence of these biases leads to a systematic underestimate of the impact of obesity on premature mortality . Although these biases preclude a valid assessment of optimal weight from existing data , available evidence suggests that minimum mortality occurs at relative weights at least 10 % below the US average BACKGROUND AND OBJECTIVES A high body mass index ( BMI ) is associated with lower mortality in patients undergoing hemodialysis . Short-term weight gains and losses are also related to lower and higher mortality risk , respectively . The implication s of weight gain or loss may , however , differ between obese individuals and their nonobese counterparts . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS The Current Management of Secondary Hyperparathyroidism : A Multicenter Observational Study ( COSMOS ) is an observational study including 6797 European hemodialysis patients recruited between February 2005 and July 2007 , with prospect i ve data collection every 6 months for 3 years . Time-dependent Cox proportional hazard regressions assessed the effect of BMI and weight changes on mortality . Analyses were performed after patient stratification according to their starting BMI . RESULTS Among 6296 patients with complete data , 1643 died . At study entry , 42 % of patients had a normal weight ( BMI , 20 - 25 kg/m(2 ) ) , 11 % were underweight , 31 % were overweight , and 16 % were obese ( BMI ≥ 30 kg/m(2 ) ) . Weight loss or gain ( < 1 % or > 1 % of body weight ) was strongly associated with higher rates of mortality or survival , respectively . After stratification by BMI categories , this was true in nonobese categories and especially in underweight patients . In obese patients , however , the association between weight loss and mortality was attenuated ( hazard ratio , 1.28 [ 95 % confidence interval ( CI ) , 0.74 to 2.14 ] ) , and no survival benefit of gaining weight was seen ( hazard ratio , 0.98 [ 95 % CI , 0.59 to 1.62 ] ) . CONCLUSIONS Assuming that these weight changes were unintentional , our study brings attention to rapid weight variations as a clinical sign of health monitoring in hemodialysis patients . In addition , a patient 's BMI modifies the strength of the association between weight changes with mortality BACKGROUND Although weight loss reduces risk for comorbid diseases , many observational studies suggest that weight loss is associated with increased mortality risk , leading to reluctance by clinicians to consider weight reduction as a strategy to maintain health and independence in older adults . However , whether the observed weight loss is intentional is difficult to determine and may not accurately represent the mortality risk associated with intentional weight reduction . Data from the Arthritis , Diet , and Activity Promotion Trial ( ADAPT ) were used to determine whether r and omization to a weight reduction program was associated with total mortality in overweight/obese older adults . METHODS ADAPT ( n = 318 ; mean age 69 + /- 6 years , body mass index 34 + /- 5 kg/m2 , 72 % female ) assessed the influence of weight loss ( achieved through dietary counseling and lifestyle modification ) and /or exercise on function in overweight/obese older adults with knee osteoarthritis . ADAPT ended in December 1999 . Participant vital was ascertained status through December 2006 using the National Death and Social Security Indexes . RESULTS The mortality rate for those r and omized to the 18-month weight loss intervention ( n = 159 , mean weight loss = -4.8 kg , 15 deaths ) was lower than that for those not r and omized to the weight loss intervention ( n = 159 , mean weight loss = -1.4 kg , 30 deaths ; hazard rate ratio = 0.5 , 95 % confidence interval 0.3 - 1.0 ) . Results were not appreciably changed when analyses were stratified by age , gender , baseline weight status , or magnitude of weight loss . CONCLUSIONS In older adults , intentional weight loss was not associated with increased total mortality and may reduce mortality risk . Observational studies of weight loss , especially when intentionality can not be rigorously established , may be misleading with respect to the effect of weight loss on mortality Although 25 % of US men indicate that they are trying to lose weight , the association between intentional weight loss and longevity in men is unknown . The authors analyzed prospect i ve data from 49,337 overweight ( initial body mass index > or = 27 ) white men aged 40 - 64 years who , in 1959 - 1960 , answered questions on weight change direction , amount , time interval , and intent . Vital status was determined in 1972 . Proportional hazards regression estimated mortality rate ratios for men who intentionally lost weight compared with men with no weight change . Analyses were stratified by health status and adjusted for age , initial body mass index , smoking status , alcohol intake , education , physical activity , health history , and physical symptoms . Among men with no reported health conditions ( n = 36,280 ) , intentional weight loss was not associated with total , cardiovascular ( CVD ) , or cancer mortality , but diabetes-associated mortality was increased 48 % ( 95 % confidence interval ( CI ) -7 % to + 133 % ) among those who lost 20 pounds ( 9.1 kg ) or more ; this increase was largely related to non-CVD mortality . Among men with reported health conditions ( n = 13,057 ) , intentional weight loss had no association with total or CVD mortality , but cancer mortality increased 25 % ( 95 % confidence interval -4 % to + 63 % ) among those who lost 20 pounds or more . Diabetes-associated mortality was reduced 32 % ( 95 % confidence interval -52 % to -5 % ) among those who lost less than 20 pounds and 36 % ( 95 % confidence interval -49 % to -20 % ) among those who lost more than 20 pounds . These results and those from our earlier study in women ( Williamson et al. , Am J Epidemiol 1995;141:1128 - 41 ) suggest that intentional weight loss may reduce the risk of dying from diabetes , but not from CVD . In observational studies , however , it is difficult to separate intentional weight loss from unintentional weight loss due to undiagnosed , underlying disease . Well- design ed observational studies , as well as r and omized controlled trials , are needed to determine whether intentional weight loss reduces CVD mortality The relation between relative weight and health differs between young and old . In older population s , weight change may cloud the association between a single relative weight and health outcomes . To determine whether weight or weight change is a more important determinant of mortality in a population of older adults , the authors analyzed data from the Systolic Hypertension in the Elderly Program ( 1984 - 1990 ) , a r and omized clinical trial testing the efficacy of antihypertensive drug treatment to reduce the risk of stroke in older adults ( aged 60 years or more ) with isolated systolic hypertension . After adjustment for covariates , an average annualized weight loss of at least 1.6 kg/year ( odds ratio = 4.9 ) , a weight loss between 1.6 and 0.7 kg/year ( odds ratio = 1.7 ) , a weight gain of more than 0.5 kg/year ( odds ratio = 2.4 ) , and a baseline body mass index of less than 23.6 ( odds ratio = 1.4 ) all had a significant ( p < 0.05 ) association with all-cause mortality compared with a referent group that was weight stable and of intermediate body mass index ( 23.6 to < 28.0 kg/m(2 ) ) and weight change ( -0.7 to < 0.5 kg/year ) . The authors conclude that , in older adults , dynamic measures ( e.g. , annualized weight change ) of weight change predict mortality better than do static weight measures ( e.g. , baseline body mass index ) . Even in those with high or low baseline body mass index , weight stability is associated with a lower mortality risk Summary Background The main associations of body-mass index ( BMI ) with overall and cause-specific mortality can best be assessed by long-term prospect i ve follow-up of large numbers of people . The Prospect i ve Studies Collaboration aim ed to investigate these associations by sharing data from many studies . Methods Collaborative analyses were undertaken of baseline BMI versus mortality in 57 prospect i ve studies with 894 576 participants , mostly in western Europe and North America ( 61 % [ n=541 452 ] male , mean recruitment age 46 [ SD 11 ] years , median recruitment year 1979 [ IQR 1975–85 ] , mean BMI 25 [ SD 4 ] kg/m2 ) . The analyses were adjusted for age , sex , smoking status , and study . To limit reverse causality , the first 5 years of follow-up were excluded , leaving 66 552 deaths of known cause during a mean of 8 ( SD 6 ) further years of follow-up ( mean age at death 67 [ SD 10 ] years ) : 30 416 vascular ; 2070 diabetic , renal or hepatic ; 22 592 neoplastic ; 3770 respiratory ; 7704 other . Findings In both sexes , mortality was lowest at about 22·5–25 kg/m2 . Above this range , positive associations were recorded for several specific causes and inverse associations for none , the absolute excess risks for higher BMI and smoking were roughly additive , and each 5 kg/m2 higher BMI was on average associated with about 30 % higher overall mortality ( hazard ratio per 5 kg/m2 [ HR ] 1·29 [ 95 % CI 1·27–1·32 ] ) : 40 % for vascular mortality ( HR 1·41 [ 1·37–1·45 ] ) ; 60–120 % for diabetic , renal , and hepatic mortality ( HRs 2·16 [ 1·89–2·46 ] , 1·59 [ 1·27–1·99 ] , and 1·82 [ 1·59–2·09 ] , respectively ) ; 10 % for neoplastic mortality ( HR 1·10 [ 1·06–1·15 ] ) ; and 20 % for respiratory and for all other mortality ( HRs 1·20 [ 1·07–1·34 ] and 1·20 [ 1·16–1·25 ] , respectively ) . Below the range 22·5–25 kg/m2 , BMI was associated inversely with overall mortality , mainly because of strong inverse associations with respiratory disease and lung cancer . These inverse associations were much stronger for smokers than for non-smokers , despite cigarette consumption per smoker varying little with BMI . Interpretation Although other anthropometric measures ( eg , waist circumference , waist-to-hip ratio ) could well add extra information to BMI , and BMI to them , BMI is in itself a strong predictor of overall mortality both above and below the apparent optimum of about 22·5–25 kg/m2 . The progressive excess mortality above this range is due mainly to vascular disease and is probably largely causal . At 30–35 kg/m2 , median survival is reduced by 2–4 years ; at 40–45 kg/m2 , it is reduced by 8–10 years ( which is comparable with the effects of smoking ) . The definite excess mortality below 22·5 kg/m2 is due mainly to smoking-related diseases , and is not fully explained . Funding UK Medical Research Council , British Heart Foundation , Cancer Research UK , EU BIOMED programme , US National Institute on Aging , and Clinical Trial Service Unit ( Oxford , UK ) OBJECTIVE To estimate the effect of intentional weight loss on mortality in overweight individuals with diabetes . RESEARCH DESIGN AND METHODS We performed a prospect i ve analysis with a 12-year mortality follow-up ( 1959 - 1972 ) of 4,970 overweight individuals with diabetes , 40 - 64 years of age , who were enrolled in the American Cancer Society 's Cancer Prevention Study I. Rate ratios ( RRs ) were calculated , comparing overall death rates , and death from cardiovascular disease ( CVD ) or diabetes in individuals with and without reported intentional weight loss . RESULTS Intentional weight loss was reported by 34 % of the cohort . After adjustment for initial BMI , sociodemographic factors , health status , and physical activity , intentional weight loss was associated with a 25 % reduction in total mortality ( RR = 0.75 ; 95 % CI 0.67 - 0.84 ) , and a 28 % reduction in CVD and diabetes mortality ( RR = 0.72 ; 0.63 - 0.82 ) . Intentional weight loss of 20 - 29 lb was associated with the largest reductions in mortality ( approximately 33 % ) . Weight loss > 70 lb was associated with small increases in mortality CONCLUSIONS Intentional weight loss was associated with substantial reductions in mortality in this observational study of overweight individuals with diabetes Although 40 % of US women indicate they are currently trying to lose weight , the association between intentional weight loss and longevity is unknown . The authors analyzed prospect i ve data from 43,457 overweight , never-smoking US white women aged 40 - 64 years who in 1959 - 1960 completed a question naire that included questions on weight change direction , amount , time interval , and intentionality . Vital status was determined in 1972 . Proportional hazards regression was used to estimate mortality rate ratios for women who intentionally lost weight compared with women who had no change in weight . Women who died within the first 3 years of follow-up were excluded . Analyses were stratified by preexisting illness and adjusted for age , beginning body mass index , alcohol intake , education , physical activity , and health conditions . In women with obesity-related health conditions ( n = 15,069 ) , intentional weight loss of any amount was associated with a 20 % reduction in all-cause mortality , primarily due to a 40 - 50 % reduction in mortality from obesity-related cancers ; diabetes-associated mortality was also reduced by 30 - 40 % in those who intentionally lost weight . In women with no preexisting illness ( n = 28,388 ) , intentional weight loss of > or = 20 lb ( > or = 9.1 kg ) that occurred within the previous year was associated with about a 25 % reduction in all-cause , cardiovascular , and cancer mortality ; however , loss of < 20 lb ( < 9.1 kg ) or loss that occurred over an interval of > or = 1 year was generally associated with small to modest increases in mortality . The association between intentional weight loss and longevity in middle-aged overweight women appears to depend on their health status . Intentional weight loss among women with obesity-related conditions is generally associated with decreased premature mortality , whereas among women with no preexisting illness , the association is equivocal In most prospect i ve studies involving older subjects , weight loss is associated with increased mortality . The authors examined the characteristics and health status of middle-aged men from 24 towns ( the British Regional Heart Study ) , who reported that they had lost weight intentionally or unintentionally as they aged . Question naires were completed at screening ( 1978 - 1980 ) , 5 years later , and in 1992 and 1996 . This paper concerns the 4,713 men who reported their weight in 1992 and 1996 and their perceived weight change over this period . Weight loss was reported by 847 men ( 18 % ) , of whom 39 % stated that it was intentional . Compared with intentional weight loss , unintentional weight loss was associated with lower social class , more smoking , less obesity , and less physical activity and with the highest rates of " poor health,"long-st and ing disability , cancer , and respiratory diseases . The rates of recalled heart attack , stroke , diabetes , and cardiovascular hospitalization were higher than among men whose weight was stable . Men who lost weight intentionally had been more obese than those who lost weight unintentionally and had high rates of obesity-related conditions . Thus , both intentional and unintentional weight loss may follow the development of disease . These findings probably account for the lack of benefit and the increased mortality associated with weight loss observed in most large-scale prospect i ve studies BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P<0.001 for both comparisons between the groups ) . The cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P<0.001 ) in the intervention group . The reduction in the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects Context Although being overweight is associated with many adverse health outcomes , observational studies of weight loss show associations between weight loss and increased mortality . This may be because these studies did not distinguish between intentional and unintentional weight loss . Contribution In a national survey of 6391 U.S. adults , people who were trying to lose weight had decreased mortality whether they lost weight or not . Lowest mortality was associated with modest intentional weight loss . People who lost weight unintentionally had increased mortality . Implication s Weight loss has adverse associations with mortality only if it is unintentional . Trying to lose weight may have benefit even if people do not actually lose weight . The Editors Despite the many health risks associated with being overweight ( 1 , 2 ) , the effect of weight loss on long-term health and longevity remains controversial ( 3 - 5 ) . R and omized clinical studies in overweight persons have shown that weight loss leads to short-term improvements in physiologic risk factors ( 6 ) and can prevent or delay hypertension and diabetes ( 7 - 9 ) . However , only observational studies have examined the effect of weight loss on mortality rates ( 3 - 5 ) and have typically found weight loss to be associated with increased rather than decreased mortality ( 3 - 5 , 10 , 11 ) . Most observational studies examining weight change and subsequent mortality rates have not assessed weight loss intention . The few studies that have tried to differentiate between the effects of intentional and unintentional weight loss have yielded mixed results ( 12 - 18 ) . The Cancer Prevention Study I and the Malm Prevention Study found that intentional weight loss was associated with reduced mortality rates among persons with diabetes ( 17 ) , impaired glucose tolerance ( 18 ) , and other health conditions ( 12 , 16 ) . Other studies , however , have found no effect of intentional weight loss on mortality rates ( 12 - 16 ) . Another concern is that self-identified intention to lose weight may indicate a healthy lifestyle or better access to health care rather than a biologically protective effect of weight loss . In 1989 , part of the National Health Interview Survey , a nationally representative sample of the U.S. population ( 19 ) , examined intent to lose weight and self-reported weight change . Death among members of this sample was followed through 1997 ( 20 ) . Using these data , we estimated the association of weight change and intention to lose weight with all-cause mortality among overweight and obese U.S. adults . Methods Study Design and Study Sample The National Health Interview Survey is an ongoing nationwide survey of health status , conditions , and behaviors among the U.S. noninstitutionalized population ( 19 , 20 ) . The survey uses a multistage , probability-sampling strategy to select approximately 45 000 households and 120 000 persons yearly . Data are weighted to match the age , sex , and ethnicity distributions of the U.S. population and to account for survey nonresponse . In this study , we used data from a supplemental survey conducted in 1989 that assessed intentional weight loss in a r and om sub sample of 20 847 adults older than 18 years of age ( 19 ) . Sufficient data were available to link 20 439 respondents ( 98 % ) to the National Death Index , providing follow-up of vital status through December 1997 ( up to 9 years ) . At this time , all survivors were censored ( 20 ) . The National Death Index is a computerized data base with st and ard identifying information about virtually all deaths in the United States and has been shown to have a high rate of ascertainment ( 21 ) . We used an algorithm provided by the National Center for Health Statistics to determine which matches should be classified as deaths ( 20 ) . Of the 20 439 persons for whom we had both survey and vital status information , we excluded 11 642 whose body mass index ( BMI ) was less than 25 kg/m2 before weight loss , since weight loss is not typically indicated for such persons . We also excluded 2328 persons younger than 35 years of age because the mortality rate in this group is extremely low ( 1.5 deaths per 1000 persons per year compared with 15.4 deaths per 1000 persons per year for those > 35 years of age ; hazard rate ratio [ HRR ] , 0.10 [ 95 % CI , 0.06 to 0.15 ] ) . Finally , we excluded 78 persons with missing data on weight loss or other covariates , leaving 6391 overweight and obese persons for the analyses . Measurements Interviewers determined age , ethnicity , sex , smoking status , self-rated health ( on a five-point scale from excellent to poor ) , hospitalizations in the past year , physician visits , days spent in bed during the past year , and chronic and acute conditions that caused hospitalizations or days spent in bed . Participants were also asked whether they were limited in any activities or work because of an impairment or health problem ; if they answered yes , they were asked to report the primary and secondary limiting health conditions that led to the impairment . Self-reported height and weight were used to compute BMI . To assess intentional weight loss , participants were asked , Have you tried to lose weight in the past year ? ; Is your weight now more , less , or about the same as a year ago ? ; and In the past year , about how much have you gained or lost ? Statistical Analyses Chi-square and analysis of variance tests were used to compare study covariates at baseline across weight loss intent and weight change groups . We used Cox proportional-hazards regression analyses to determine the mortality HRR associated with weight loss intention and weight change while adjusting for potentially confounding variables . The HRR is the ratio of two rates of disease or mortality occurrence . It is a relative measure of how rapidly cases of disease or death occur in a group with the risk factor compared with the group without the risk factor . We found no violation of the statistical assumptions underlying the proportional hazards regression in graphical or statistical examinations . Similarly , we found no problematic influential data points or multicollinearity . We also computed predictive margins to estimate the multivariate-adjusted 8-year cumulative hazard rate ( equivalent to the mean follow-up ) for each weight loss intent and weight change group ( 22 ) . Predictive margins are a type of direct st and ardization in which predicted values from the Cox proportional-hazards regression models are averaged over the covariate distribution in the sample . Because we found a statistically significant interaction between weight loss intent and weight change , we stratified weight change according to whether persons reported trying to lose weight . Multivariate models controlled for age , ethnicity , sex , smoking , education , initial BMI , measures of health status ( self-rated health and days spent in bed during the past year ) , diabetes ( none , noninsulin treated , insulin treated ) , cardiovascular disease or cancer cited as a cause of functional limitation , number of acute and chronic conditions , and measures of health care utilization ( hospitalizations and physician visits during the past year ) . We also evaluated models that excluded smokers , since smokers are at increased risk for death and may be more likely to lose weight . We tested for interactions between weight loss intent and weight loss group and age ( 35 to 64 years vs. 65 years ) , sex , and BMI ( < 30 kg/m2 vs. 30 kg/m2 ) to determine the association with mortality . We computed poststratification weights to account for the 78 missing participants and conducted analyses using SUDAAN , version 7.5.4a ( Research Triangle Institute , Research Triangle Park , North Carolina ) , to make the study estimates statistically representative of the U.S. noninstitutionalized population of overweight and obese adults 35 years of age and older . SUDAAN uses Taylor series linearization to estimate variances , allowing analyses to account for the unequal weighting , stratification , and clustering . Role of the Funding Source The authors analyzed the data and wrote this article as employees of the U.S. Centers for Disease Control and Prevention . The Centers for Disease Control and Prevention was therefore involved in the analysis and interpretation of the data and in the decision to su bmi t the paper for publication . Results Fifty-eight percent , 12 % , and 30 % of participants reported no weight change , weight gain , and weight loss , respectively ( Table 1 ) . Compared with persons reporting stable weight , those who reported gaining or losing weight were more likely to be women , to report worse overall health and more days in bed , and to have had functional limitations , physician visits , and hospitalizations during the previous year . Persons who lost weight also had higher baseline BMI s and were more likely to be smokers , to have diabetes , and to have been hospitalized during the previous year than persons with stable weight or weight gain . Table 1 . Characteristics of 6391 Overweight Persons , according to Weight Loss Intention and Reported Weight Change Fifty-eight percent of the study participants reported trying to lose weight during the previous year ( Table 1 ) . Persons who were trying to lose weight reported more weight loss than those who were not trying to lose weight ( P < 0.001 ) , but the magnitude of this difference was small ( median weight change , 0.4 kg vs. 0.3 kg ) . Compared with persons who were not trying to lose weight , those who reported attempted weight loss were more likely to be women and to have diabetes , were younger , were more likely to be of white ethnicity and nonsmokers , had higher BMI s , and were less likely to report fair or poor health . Persons attempting weight loss also reported more physician visits and more days in bed during the previous year than those who were not trying to lose weight . During 9 years of follow-up ( mean , 8.0 years ) , 892 participants died ( age-adjusted rate , 17.8 deaths per 1000 person-years ) . Compared with persons with no weight change , OBJECTIVE To determine how change in BMI over 8 years is associated with risk of subsequent cardiovascular disease ( CVD ) among middle aged men . METHODS Prospect i ve cohort study among 13,230 healthy men ( aged 51.6+/-8.7 years ) in the Physicians ' Health Study . BMI was collected at baseline in 1982 and after 8 years , at which time follow-up began . Subsequent CVD events were collected and confirmed through March 31 , 2005 . Cox proportional hazards models evaluated BMI at 8 years and risk of CVD , 8-year change in BMI and risk of CVD , and whether change in BMI added prognostic information after the consideration of BMI at 8 years . RESULTS 1308 major CVD events occurred over 13.5 years . A higher BMI at year 8 was associated with an increased risk of CVD . Compared to a stable BMI ( + /-0.5 kg/m(2 ) ) , a 0.5 - 2.0 kg/m(2 ) increase had a multivariable-adjusted RR of 1.00 ( 0.86 - 1.16 ) . A > /=2.0 kg/m(2 ) increase had a multivariable-adjusted RR of 1.39 ( 1.16 - 1.68 ) , however further adjustment for BMI reduced the RR to 1.00 ( 0.81 - 1.23 ) . A decrease in BMI had a multivariable RR of 1.23 ( 1.07 - 1.42 ) which was unaffected by adjustment for BMI at 8 years . CONCLUSION A higher BMI and a rising BMI were both associated with an increased risk of CVD , however an increasing BMI did not add prognostic information once current BMI was considered . In contrast , a declining BMI was associated with an increased risk of CVD independent of current BMI Observational studies have established that obesity is associated with a substantially increased risk of developing type 2 diabetes.1 Whether intentional weight loss reduces the risk of obese persons ’ developing diabetes remains unclear , however . Two r and omized controlled trials for the primary prevention of type 2 diabetes in adults have included lifestyle intervention arms emphasizing modest weight loss.2,3 Relatively few observational studies have examined the association of weight loss with diabetes risk,4 and no published observational study has differentiated the effects of intentional weight loss from those of unintentional weight loss . This is important because unintentional weight loss may be associated with the clinical onset of diabetes.5 This is the first observational study to use data on weight-loss intention in examining the prospect i ve relationship between weight change and the incidence of diabetes in overweight adults OBJECTIVE To examine the effect of reverse causality and confounding on the association of BMI with all-cause and cause-specific mortality . RESEARCH METHODS AND PROCEDURES Data from two large prospect i ve studies were used . One ( a community-based cohort ) included 8327 women and 7017 men who resided in two Scottish towns at the time of the baseline assessment in 1972 - 1976 ; the other ( an occupational cohort ) included 4016 men working in the central belt of Scotl and at the time of the baseline assessment in 1970 - 1973 . Participants in both cohorts were ages 45 to 64 years at baseline ; the follow-up period was 28 to 34 years . RESULTS In age-adjusted analyses that did not take account of reverse causality or smoking , there was no association between being overweight ( BMI 25 to < 30 kg/m(2 ) ) and mortality , and weak to modest associations between obesity ( BMI > or = 30 kg/m(2 ) ) and mortality . There was a strong association between smoking and lower BMI in women and men in both cohorts ( all p < 0.0001 ) . Among never-smokers and with the first 5 years of deaths removed , overweight was associated with an increase in all-cause mortality ( relative risk ranging from 1.12 to 1.38 ) , and obesity was associated with a doubling of risk in men in both cohorts ( relative risk , 2.10 and 1.96 , respectively ) and a 60 % increase in women ( relative risk , 1.56 ) . In both never-smokers and current smokers , being overweight or obese was associated with important increases in the risk of cardiovascular disease . DISCUSSION These findings demonstrate that with appropriate control for smoking and reverse causality , both overweight and obesity are associated with important increases in all-cause and cause-specific mortality , and in particular with cardiovascular disease mortality Several epidemiologic investigations have suggested that weight loss is associated with increased mortality risk but have not examined whether the weight loss was intentional or unintentional . The authors examined whether the association between weight loss and mortality differs by whether the weight loss was intentional or unintentional as part of the Iowa Women 's Health Study , a prospect i ve cohort study of health risk factors in postmenopausal women . Women aged 55 - 69 years completed questions about intentional and unintentional weight losses since age 18 years via mail survey in 1992 and were followed through 1995 . One or more intentional weight loss episodes of 20 or more pounds ( > or = 9.1 kg ) during adulthood was not significantly associated with higher total or cardiovascular disease mortality risk compared with never losing > or = 20 pounds . One or more unintentional weight loss episodes of 20 or more pounds was associated with a 26 - 57 % higher total mortality risk and a 51 - 114 % higher cardiovascular disease mortality risk , compared with never losing 20 or more pounds . Associations between unintentional weight loss and increased mortality risk were confined mostly to women with prevalent disease , hypertension , or diabetes . Patterns of association did not vary by overweight status . These findings suggest that the association between weight loss and increased mortality risk observed in epidemiologic studies may be due to unintentional weight loss that reflects existing disease and not due to intentional weight loss Identifying the benefits and adverse effects of weight loss is difficult , especially because these assessment s were not among the original goals of prospect i ve evaluations of cardiovascular disease such as the Framingham Study . Attention previously focused on obesity , body fat distribution , and alternating cycles of weight gain and weight loss as risk factors for cardiovascular disease [ 112 ] . The Technology Assessment Conference [ 13 ] emphasized voluntary weight loss and control , whereas both voluntary and involuntary weight loss occur in free-living population s for various reasons , making it difficult to separate causes from consequences and benefits from adverse effects . Nevertheless , the availability of repeated measures of weight , body size , and fatness , together with follow-up for death , morbidity , and risk factors provides an opportunity to gain useful insights into the determinants and effects of weight changes . Methods The Framingham Study recruited 5209 men and women between ages 30 and 62 years beginning in 1948 ; observations made at 2-year intervals included measurements of weight and risk factors as well as ascertainment of cardiovascular events and morbidity and death from all causes [ 3 , 1416 ] . Framingham Study Men and women between ages 35 and 54 years at the fourth examination of the Framingham cohort ( 1954 - 1958 ) were characterized with respect to change in body mass index ( BMI , kg/m2 ) measured at 2-year intervals during a period of 10 years . Those who did not attend each examination were excluded ( 18 % of those present at examination 4 ) . Individual slopes , based on regressions of BMI for six examinations , were used to define three equal groups ( tertiles ) of individuals ; characterizing approximately those who lost , those who remained relatively stable , and those who gained . Details of examination procedures , laboratory methods , diagnostic criteria , and follow-up methods have been published [ 3 , 1416 ] . This report defined cardiovascular disease as coronary heart disease , stroke , intermittent claudication , and congestive heart failure . Coronary heart disease was defined as myocardial infa rct ion , coronary insufficiency , and angina pectoris . Hypertension was defined by a blood pressure 160 mm Hg ( systolic ) or 95 mm Hg ( diastolic ) or by the use of antihypertensive medication . Pulmonary disease was diagnosed clinical ly or by self-report of chronic coughing or wheezing . Other clinical ly diagnosed diseases included mitral or aortic valve disease , arthritis , urinary disease , neurologic disease , and other vascular disease . The term any disease applied to any of these conditions . Statistical Analysis Individual slopes of weight , BMI , systolic blood pressure , diastolic blood pressure , and cholesterol were estimated for the 10-year period from examination 4 to examination 9 . The coefficient of variation was defined as the st and ard deviation of BMI divided by the mean BMI for examinations 4 through 9 . The variability around the BMI slope for examinations 4 through 9 was calculated as Equation 1 where y = predicted BMI , y = actual BMI , and df = degrees of freedom . Mean BMI s for examinations 4 through 9 were calculated for the population attending all of these examinations ; means for examinations 1 through 3 and 10 through 18 were based on members of this population who attended the examination in question . Results from the first and third tertiles ( loss and gain groups ) were compared with those from the no change group using t-tests for continuous variables and chi-square analyses for dichotomous variables . Changes in lipid levels , blood pressure , and smoking status by change in weight were compared using analysis of variance and chi-square tests . Mortality rates were calculated for the cohort during 20 years of follow-up and excluded deaths occurring in the first 4 years . Age-adjusted and multivariate relative risks and 95 % confidence intervals ( CIs ) were calculated from Cox regression coefficients with age , and age plus major risk factors at examination 9 in the models . In these regression analyses , the tertiles of BMI slope were entered as dummy variables and used the middle group as the referent . Results Figure 1 shows the age-adjusted mean levels of BMI for the three tertiles of BMI change for the 10-year classification period ( examinations 4 through 9 ) , together with mean levels of BMI for 6 years before and 18 years after this period . Each group has been subdivided into those who survived through examination 18 and those who died between examinations 9 and 18 . Values of BMI were not available for those who did not return for any of examinations 10 through 18 because of death or for any other reason . In all three groups of BMI change , mean BMI s for those who survived through examination 18 were stable during follow-up . Figure 1 . Mean body mass index at examinations 1 through 18 . Among women whose BMI s decreased , the decline was greater and continued beyond examination 9 in the 31 % who did not survive to examination 18 . The absence of a similar pattern among men whose BMI s decreased may have been due to the higher proportion of these men ( 53 % ) who did not survive to examination 18 . Twenty-eight percent of deaths were attributed to coronary heart disease in these men , and 15 % were sudden , whereas 19 % were attributed to coronary heart disease in women whose BMI s decreased , and 6 % were sudden . Among men in the no-change group , mean BMI s were higher in those who died than in those who survived . Mean BMI s were similar , however , in these two groups of women . Among men who gained weight between examinations 4 and 9 , those who died before examination 18 were heavier initially , but their BMI s decreased sharply toward the end of the follow-up period . A similar pattern was seen in women , but the discrepancy in BMI was greater . Those who did not survive were heavier until 8 years of follow up , when BMI s decreased sharply in those who did not survive to examination 18 . Characteristics of the three BMI change groups during the classification period ( examinations 4 through 9 ) are shown in Table 1 . Weight loss ranged from losses of 24.4 and 24.0 kg ( 54 and 53 lb ) to gains of 2.2 and 7.7 kg ( 5 and 17 lb ) for men and women , respectively , in the BMI loss tertile . Men and women whose BMI s decreased were older ; their mean BMI s were 27.1 and 25.7 at examination 4 and 25.3 and 24.2 at examination 9 . They were the heaviest groups at the beginning and the lightest groups at the end of this period ; BMI s averaged for the six examinations were identical for the three groups of men but were lowest for women whose BMI did not change . Change in BMI correlated weakly with BMI at examination 4 ( r = 0.2 and 0.12),with mean BMI for examinations 4 through 9 ( r = 0.05 and 0.11 ) , with the coefficient of variation ( r = 0.06 and 0.19 ) , and with variability around the BMI slope ( r = 0.04 and 0.12)for men and women , respectively . The coefficient of variation ( variability around the mean ) and variability around the slope of BMI were greater for those whose BMI s decreased or increased ( Table 1 ) . Table 1 . Means of Selected Measures by Tertile of Change in Body Mass Index among Framingham Men and Women between Ages 35 and 54 Years Compared with those whose BMI s were unchanged , men and women whose BMI s decreased had higher systolic blood pressures and cholesterol levels initially but not at the end of the baseline period . Rates of cigarette smoking at examinations 4 and 9 were higher among those whose BMI s decreased , and the percentages of smokers who quit were lower among those whose BMI s decreased than among those whose BMI s changed only slightly . Rates of smoking cessation were twice as high in men and women who gained as in those who lost weight . Levels of physical activity were similar in the three groups of men but were slightly lower in the BMI loss group of women . At examination 7 or 8 , 16 % of men and women who lost weight were on weight control diets ; 20 % of women and 9 % of men who gained and 11 % of women and 7 % of men whose weight remained unchanged reported being on similar diets . Average annual changes in weight and the major cardiovascular risk factors during the 10-year period are also shown in Table 1 . Among men of average height ( 1.7 m [ 68 in ] ) , the average annual weight change for the three tertiles of BMI change ranged from a loss of 0.51 kg ( 1.14 lb ) to a gain of 0.60 kg ( 1.33 lb ) . Among women of average height ( 1.6 m [ 63 in ] ) , average annual changes in weight varied from a loss of 0.39 kg ( 0.86 lb ) to a gain of 0.71 kg ( 1.58 lb ) . Women with the most stable weights gained an average of 0.16 kg ( 0.36 lb ) per year . Systolic and diastolic blood pressures increased least in those whose BMI decreased and increased most in those whose BMI s increased . Changes in cholesterol levels ranged from a decrease of 0.02 mmol/L ( 0.76 mg/dL ) per year for men who lost weight to increases of 0.01 to 0.02 mmol/L ( 0.38 to 0.76 mg/dL ) per year for those whose weight increased or remained unchanged . Changes in cholesterol were all positive in women , ranging from increases of 0.03 mmol/L ( 1.1 mg/dL ) per year for those who lost weight to increases of 0.06 mmol/L ( 2.3 mg/dL ) for other women . In contrast , rates of smoking cessation were more beneficial for health , that is , higher in those whose BMI s increased . Prevalence rates of cardiovascular disease and coronary heart disease were significantly higher at examination 9 among men whose BMI s decreased ( see Table 1 ) ; diabetes , pulmonary disease , and the aggregate of all diseases were similarly more prevalent among men in this group than among those whose BMI s did not change . Diabetes was the only condition that was significantly more frequent in those whose BMI s increased than in those whose BMI s remained unchanged . Among women , prevalence rates of hypertension , pulmonary conditions , and any disease were significantly higher at examination 9 among those whose BMI s decreased than among those whose BMI s did not OBJECTIVES To describe the incidence , anthropometric parameters , and clinical significance of weight loss in older out patients . DESIGN Four-year prospect i ve cohort study . SETTING University-affiliated Veterans Affairs Medical Center . PATIENTS Two hundred forty-seven community-dwelling male veterans 65 years of age or older . MEASUREMENTS Anthropometrics ( weight , height , skin-folds , and circumferences ) , health status measures ( Sickness Impact Profile scores , health care utilization , self-reported ratings of health ) , and bloodwork ( cholesterol , albumin , others ) were obtained at baseline and followed annually for 2 years . Outcome measures ( hospitalization , nursing home placement , and mortality rates ) were followed for a minimum of 2 years after any identified weight change . MAIN RESULTS The mean annual percentage weight change for the study population was -0.5 % ( SD : + /- 4.0 % ; range : -17 % to + 25 % ) . Four percent annual weight loss was determined to be the optimal cutpoint for defining clinical ly important involuntary weight loss using ROC curve analysis . The annual incidence of this degree of involuntary weight loss was 13.1 % . At baseline , involuntary weight losers were similar to nonweight losers in age ( 73.9 + /- 7.9 vs 73.3 + /- 6.7 years ) , body mass index ( 26.8 + /- 3.9 vs 26.9 + /- 4.1 kg/m2 ) , and all other anthropometric , health status , and laboratory measures . Relative to nonweight losers , involuntary weight losers had significantly ( P < or = .05 ) greater decrements in central skinfold and circumference measures ( subscapular skinfolds , -2.9 vs -0.4 mm ; suprailiac skinfolds , -4.2 vs -0.2 mm ; and waist to hip ratio , -.01 vs + .00 ) . Both groups had significant decreases in their triceps skinfolds ( an estimate of peripheral subcutaneous fat ) , whereas arm muscle area and albumin levels did not decline significantly in either group . Over a 2-year follow-up period , mortality rates were substantially higher ( RR = 2.43 ; 95 % CI = 1.34 - 4.41 ) among involuntary weight losers ( 28 % ) than among nonweight losers ( 11 % ) . Of interest , a similar increase in 2-year mortality ( 36 % ) was also observed among subjects with voluntary weight loss ( by dieting ) . Survival analyses adjusting for differences between weight losers and nonweight losers in baseline age , BMI , tobacco use , and other health status and laboratory measures yielded similar results . CONCLUSIONS These results indicate that involuntary weight loss occurred frequently ( 13.1 % annual incidence ) in this population of older veteran out patients . When involuntary weight loss occurred , the predominant anthropometric changes were decrements in measures of central ly distributed fat ( trunkal skinfolds and circumferences ) . Finally , involuntary weight loss greater than 4 % of body weight appears to be clinical ly important as an independent predictor of increased mortality OBJECTIVE To evaluate the relationship between measured weight , weight change , and 6-year mortality risk in a r and om sample of 648 community-dwelling women aged 65 and older from Baltimore , Maryl and . MEASUREMENTS Data were collected using a st and ardized question naire and administered in person by trained interviewers . Question naires were completed annually from 1984 to 1986 , and body weight was measured at each interview . Weight was defined as body mass index ( BMI ) of low ( < 23 kg/m2 ) , average ( > or = 23 kg/m2 to < or = 28 kg/m2 ) , and high ( > 28 kg/m2 ) . Four mutually exclusive categories of weight change of at least 4.5 % in BMI over the three annual interviews were developed to describe all possible weight change patterns : weight gain , weight loss , no change , and weight cycling . RESULTS During the follow-up period , 106 women ( 16 % ) died . Women with low baseline BMI , regardless of weight change , and those who lost weight , regardless of baseline BMI had increased mortality risk . Women with average baseline BMI and weight loss had a very high mortality risk ( hazard ratio ( HR ) 3.84 , 95 % Confidence interval ( CI ) 2.14 - 6.89 ) . Women who weight cycled had increased mortality risk at low and high baseline weights , and a nonsignificant increased risk at average baseline weight ( P = .069 ) . Analyses were adjusted for age , education , smoking , alcohol usage , and pre-existing illness and included an interaction between weight change and baseline BMI . CONCLUSIONS These results suggest that white , older , community-dwelling women are at an increased risk of mortality if they are underweight , lose weight , or weight cycle BACKGROUND Weight loss is associated with short-term amelioration and prevention of metabolic and cardiovascular risk , but whether these benefits persist over time is unknown . METHODS The prospect i ve , controlled Swedish Obese Subjects Study involved obese subjects who underwent gastric surgery and contemporaneously matched , conventionally treated obese control subjects . We now report follow-up data for subjects ( mean age , 48 years ; mean body-mass index , 41 ) who had been enrolled for at least 2 years ( 4047 subjects ) or 10 years ( 1703 subjects ) before the analysis ( January 1 , 2004 ) . The follow-up rate for laboratory examinations was 86.6 percent at 2 years and 74.5 percent at 10 years . RESULTS After two years , the weight had increased by 0.1 percent in the control group and had decreased by 23.4 percent in the surgery group ( P<0.001 ) . After 10 years , the weight had increased by 1.6 percent and decreased by 16.1 percent , respectively ( P<0.001 ) . Energy intake was lower and the proportion of physically active subjects higher in the surgery group than in the control group throughout the observation period . Two- and 10-year rates of recovery from diabetes , hypertriglyceridemia , low levels of high-density lipoprotein cholesterol , hypertension , and hyperuricemia were more favorable in the surgery group than in the control group , whereas recovery from hypercholesterolemia did not differ between the groups . The surgery group had lower 2- and 10-year incidence rates of diabetes , hypertriglyceridemia , and hyperuricemia than the control group ; differences between the groups in the incidence of hypercholesterolemia and hypertension were undetectable . CONCLUSIONS As compared with conventional therapy , bariatric surgery appears to be a viable option for the treatment of severe obesity , result ing in long-term weight loss , improved lifestyle , and , except for hypercholesterolemia , amelioration in risk factors that were elevated at baseline OBJECTIVE To examine the relationship between weight change and duration of overweight and obesity and the incidence of type 2 diabetes in a cohort of middle-aged British men . RESEARCH DESIGN AND METHODS We carried out a prospect i ve study of cardiovascular disease in men aged 40 - 59 years at screening ( 1978 - 1980 ) , drawn from one general practice in 24 British towns , who completed a postal question naire 5 years later ( Q5 ) and for whom data on BMI at year 1 ( Q1 ) and Q5 were available ( n = 7,100 ) . Men with diabetes at Q1 or Q5 and men with hyperglycemia at Q1 were excluded from the study ( n = 184 ) . The main outcome measure was type 2 diabetes ( physician-diagnosed ) during a mean follow-up period of 12 years starting at Q5 ( 1983 - 1985 ) . RESULTS In the 6,916 men with no history or evidence of diabetes , there were 237 incident cases of type 2 diabetes during the mean follow-up period of 12 years , a rate of 3.2/1,000 person-years . Substantial weight gain ( > 10 % ) was associated with a significant increase in risk of type 2 diabetes compared with that in men with stable weight ( relative risk [ RR ] 1.61 [ 95 % CI 1.01 - 2.56 ] ) after adjustment for age , initial BMI , and other risk factors . Excluding men who developed diabetes within 4 years after the period of weight change increased the risk further ( 1.81 [ 1.09 - 3.00 ] ) . After adjustment and exclusion of men who developed diabetes early in the follow-up , weight loss ( > or = 4 % ) was associated with a reduction in the risk of type 2 diabetes , compared with that in the stable group , that reached marginal significance ( 0.65 [ 0.42 - 1.03 ] , P = 0.07 ) . A test for trend that fitted weight change as a continuous covariate showed the risk of diabetes to increase significantly from maximum weight loss to maximum weight gain ( P = 0.0009 ) . The lower risk associated with weight loss was seen in obese ( > or = 28 kg/m2 ) and nonobese subjects and in men with normal ( < 6.1 mmol/l ) and high ( > or = 6.1 mmol/l ) nonfasting blood glucose levels . Although not statistically significant , this is consistent with a benefit from weight loss . Risk of type 2 diabetes increased progressively and significantly with increasing levels of initial BMI and also with the duration of overweight and obesity ( P<0.0001 ) . CONCLUSIONS This study confirms the critical importance of overweight and obesity , particularly of long duration , in the development of type 2 diabetes . The data support current public health recommendations to reduce the risk of type 2 diabetes by preventing weight gain in middle-aged men who are not overweight and by encouraging weight loss in overweight and obese men We prospect ively evaluated 91 patients with involuntary weight loss . Thirty-two ( 35 % ) had no identifiable physical cause of weight loss , whereas the remainder had various physical illnesses . During the year after the index visit , 23 ( 25 % ) of the patients died and another 14 ( 15 % ) deteriorated clinical ly . Physical causes of weight loss were clinical ly evident on the initial evaluation in 55 of 59 patients . The four patients in whom the diagnosis was initially missed had cancer , and in only one of these patients was the illness truly occult . Because diagnoses were usually made rapidly in patients with a physical cause of weight loss , we conclude that involuntary weight loss is rarely due to " occult " disease . We developed a decision rule that used six attributes to correctly identify 57 of 59 patients ( 97 % ) with a physical cause of weight loss and 23 of 32 patients without . Thus , our rule may help in the early triage of patients with involuntary weight loss BACKGROUND The possible adverse health effects of weight cycling ( weight loss followed by weight regain ) have been the subject of recent concern . To determine whether such weight cycling negatively influences cardiovascular risk factors , 153 overweight individuals were followed up prospect ively through a 30-month weight loss and maintenance program . METHODS Subjects were divided into seven groups according to their weight-change patterns during this 30-month study ( steady weight loss of different magnitudes , weight gain , no change in weight , and different weight-cycling patterns ) . These weight-change groups were compared with regard to lipid levels , blood pressure measurements , waist-to-hip ratio , and percent body fat at 0 , 6 , 12 , 18 , and 30 months . RESULTS No adverse effects of weight cycling on any of the cardiovascular risk factors were observed . Subjects who initially lost 9.0 kg or more and then regained it did not differ from those who had no change in weight with regard to any cardiovascular risk factor at month 30 . Subjects who gained weight during the 30-month interval increased their risk factors , those who lost weight decreased their risk factors in proportion to the magnitude of weight loss , and , in general , cardiovascular risk factors at month 30 were related to the net weight loss achieved and not the route taken to achieve the weight loss . CONCLUSIONS This study showed no negative effects of weight cycling on cardiovascular risk factors and confirmed previous findings of positive effects of weight loss on risk factors . Therefore , overweight individuals should be encouraged to lose weight and then maintain their weight loss BACKGROUND We have examined the relationship between intentional and unintentional weight loss and the reasons underlying intention to lose weight and all-cause mortality and mortality due to cardiovascular disease ( CVD ) and non-CVD causes in older men . METHODS Prospect i ve study of 4869 men aged 56 to 75 years drawn from general practice s in 24 British towns , who in 1996 completed question naires about intentional and unintentional weight loss over the preceding 4 years and were followed up for a subsequent 7 years . RESULTS Unintentional but not intentional weight loss was associated with a significant increase in risk of all-cause mortality compared with men who reported no weight change , even after adjustment for lifestyle characteristics and preexisting disease ( adjusted relative risk [ RR ] , 1.71 ; 95 % confidence interval [ CI ] , 1.33 - 2.19 ; and RR , 1.00 ; 95 % CI , 0.91 - 1.10 , respectively ) . Men who lost weight intentionally as a result of personal choice showed significant benefit in all-cause mortality ( RR , 0.59 ; 95 % CI , 0.34 - 1.00 ; P = .05 ) , which was largely owing to a significant reduction in mortality from non-CVD causes ( RR , 0.36 ; 95 % CI , 0.15 - 0.87 ) . The benefit in these men was most apparent in markedly overweight men ( BMI [ calculated as weight in kilograms divided by the square of height in meters ] > or = 28 ) and in younger men ( age < 65 years ) . Men who lost weight intentionally owing to ill health or physician 's advice showed an increased risk of all-cause mortality ( RR , 1.37 ; 95 % CI , 0.96 - 1.94 ) . No harm or benefit was seen for CVD mortality , irrespective of reasons for intentional weight loss . CONCLUSION Intentional weight loss carried out for personal reasons is associated with a significant reduction in all-cause mortality in markedly overweight men , and the data suggest that the earlier the intervention , the greater the chance of benefit Background and aims : Weight changes are predictors of health outcomes in older people . The purpose of this study is to examine the association between 2-year weight change and mortality in older Mexican Americans . Methods : Seven-year prospect i ve cohort study of 1749 non-institutionalized Mexican American men and women aged 65 and older residing in five Southwestern states . Measures include self-reports of medical conditions ( heart attack , stroke , diabetes , hypertension , hip fracture or cancer ) , functional disability , high depressive symptoms , smoking status , a summary performance score of lower body function , h and grip muscle strength , and body mass index ( BMI ) . Weight change was examined by comparing the baseline weight to the weight two years later to estimate the hazard of death within the following five-year period . Results : Of the 1749 subjects , 396 ( 22.6 % ) lost 5 % or more weight , 984 ( 56.3 % ) had weight that remained stable , and 369 ( 21.1 % ) gained 5 % or more weight between baseline and the 2-year follow-up period . Of the ones who lost 5 % of weight , 28 % died as compared to 19.7 % and 15.2 % of those whose weight remained stable and those who gained weight after 5 years , respectively . The hazard ratio ( HR ) of death for the group that lost 5 % or more of their weight compared to the reference group ( stable weight ) was 1.35 ( 95 % CI 1.06–1.70 ) after controlling for demographic variables , BMI , and waist circumference at baseline and 1.32 ( 95 % CI 1.04–1.67 ) after controlling for all covariates . The HR of death for the group that gained 5 % or more of weight was 0.78 ( 95 % CI 0.58–1.05 ) after controlling for demographic variables , BMI , and waist circumference at baseline and 0.77 ( 95 % CI 0.57–1.04 ) after controlling for all covariates . Conclusions : Weight loss is an independent predictor of mortality among older Mexican Americans , after controlling for relevant risk factors Abstract Objective To investigate the association of predicted lean body mass , fat mass , and body mass index ( BMI ) with all cause and cause specific mortality in men . Design Prospect i ve cohort study . Setting Health professionals in the United States Participants 38 006 men ( aged 40 - 75 years ) from the Health Professionals Follow-up Study , followed up for death ( 1987 - 2012 ) . Main outcome measures All cause and cause specific mortality . Results Using vali date d anthropometric prediction equations previously developed from the National Health and Nutrition Examination Survey , lean body mass and fat mass were estimated for all participants . During a mean of 21.4 years of follow-up , 12 356 deaths were identified . A J shaped association was consistently observed between BMI and all cause mortality . Multivariable adjusted Cox models including predicted fat mass and lean body mass showed a strong positive monotonic association between predicted fat mass and all cause mortality . Compared with those in the lowest fifth of predicted fat mass , men in the highest fifth had a hazard ratio of 1.35 ( 95 % confidence interval 1.26 to 1.46 ) for mortality from all causes . In contrast , a U shaped association was found between predicted lean body mass and all cause mortality . Compared with those in the lowest fifth of predicted lean body mass , men in the second to fourth fifths had 8 - 10 % lower risk of mortality from all causes . In the restricted cubic spline models , the risk of all cause mortality was relatively flat until 21 kg of predicted fat mass and increased rapidly afterwards , with a hazard ratio of 1.22 ( 1.18 to 1.26 ) per st and ard deviation . For predicted lean body mass , a large reduction of the risk was seen within the lower range until 56 kg , with a hazard ratio of 0.87 ( 0.82 to 0.92 ) per st and ard deviation , which increased thereafter ( P for non-linearity < 0.001 ) . For cause specific mortality , men in the highest fifth of predicted fat mass had hazard ratios of 1.67 ( 1.47 to 1.89 ) for cardiovascular disease , 1.24 ( 1.09 to 1.43 ) for cancer , and 1.26 ( 0.97 to 1.64 ) for respiratory disease . On the other h and , a U shaped association was found between predicted lean body mass and mortality from cardiovascular disease and cancer . However , a strong inverse association existed between predicted lean body mass and mortality from respiratory disease ( P for trend < 0.001 ) . Conclusions The shape of the association between BMI and mortality was determined by the relation between two body components ( lean body mass and fat mass ) and mortality . This finding suggests that the “ obesity paradox ” controversy may be largely explained by low lean body mass , rather than low fat mass , in the lower range of BMI |
792 | 30,844,560 | CONCLUSION Patients with CAD and elevated IgG aCL have a doubled risk of recurrent MACE at 12 and 24 months . | BACKGROUND Anticardiolipin antibodies of the immunoglobulin G isotype ( IgG aCL ) have been suggested as risk factor for arterial and venous thrombosis .
No conclusive data in patients with coronary artery disease ( CAD ) do exist .
We investigate the risk of recurrent CAD according to the presence of IgG aCL . | In this paper are reported the basal results of a multidisciplinary , multicenter study design ed to explore in a population with ischemic disease the relation between hemostatic variables , conventional risk factors and atherothrombotic sequelae . 953 patients less than or equal to 69 yrs with documented coronary , cerebral or peripheral atherosclerotic disease were studied and followed-up for 24 months . Examinations included hemostatic and lipid laboratory assays , arterial Doppler examination , cerebral computerized tomography and nuclear magnetic resonance , exercise electrocardiogram and coronary angiography . Fibrinogen ( 301.4 + /- 71.52 mg/dl ) correlated positively with antithrombin III ( r = 0.27 ) and leukocytes ( r = 0.25 ) , negatively with HDL-cholesterol ( r = 0.18 ) and tended to increase with smoking . Heavy smokers had higher leukocyte counts than non-smokers ( 8.0 + /- 2.0 vs. 7.2 + /- 2.1 x 10(3)/microliters ) , higher triglycerides ( 1.87 + /- 1.12 vs. 1.53 + /- 1.35 mmol/l ) and lower HDL-cholesterol ( 0.93 + /- 0.27 vs. 1.00 + /- 0.25 mmol/l ) . FVII correlated positively with triglycerides ( r = 0.16 ) and protein C ( r = 0.45 ) . vWF : Ag ( 145.4 + /- 70.58 % ) ad FVII : C ( 139.7 + /- 59.10 % ) were positively correlated ( r = 0.44 ) . FVIII : C correlated positively with fibrinogen ( r = 0.21 ) . Myocardial infa rct ion survivors with associated cerebral and peripheral vascular lesions had higher FVIII : C , FVII , fibronogen and vWF : Ag . These findings suggest that hemostatic factors may enhance and /or mediate the effects of conventional risk factors in atherothrombotic ischemic events BACKGROUND AND METHODS The use of oral anticoagulation in the long-term treatment of survivors of acute myocardial infa rct ion has been highly controversial . We therefore r and omly assigned 1214 patients who had recovered from acute myocardial infa rct ion ( mean interval from the onset of symptoms to r and omization , 27 days ) to treatment with warfarin ( 607 patients ) or placebo ( 607 patients ) for an average of 37 months ( range , 24 to 63 ) . RESULTS At the end of the treatment period , there had been 123 deaths in the placebo group and 94 in the warfarin group -- a reduction in risk of 24 percent ( 95 percent confidence interval , 4 to 44 percent ; P = 0.027 ) . A total of 124 patients in the placebo group had reinfa rct ions , as compared with 82 in the warfarin group -- a reduction of 34 percent ( 95 percent confidence interval , 19 to 54 percent ; P = 0.0007 ) . Furthermore , we observed a reduction of 55 percent ( 95 percent confidence interval , 30 to 77 percent ) in the number of total cerebrovascular accidents in the warfarin group as compared with the placebo group ( 44 vs. 20 ; P = 0.0015 ) . Serious bleeding was noted in 0.6 percent of the warfarin-treated patients per year . CONCLUSIONS Long-term therapy with warfarin has an important beneficial effect after myocardial infa rct ion and can be recommended in the treatment of patients who survive the acute phase Background —Reinfa rct ion after primary percutaneous coronary intervention in patients with ST-segment – elevation myocardial infa rct ion has negative consequences . Little is known about reinfa rct ion after drug-eluting stents and bivalirudin anticoagulation . We , therefore , sought to determine the incidence , predictors , and implication s of reinfa rct ion after primary percutaneous coronary intervention in the contemporary era . Methods and Results — Outcomes were assessed in 3202 patients undergoing stent implantation for ST-segment – elevation myocardial infa rct ion in the Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infa rct ion ( HORIZONS-AMI ) trial . Independent predictors of reinfa rct ion and mortality were identified by Cox proportional hazards modeling . The cumulative incidence of reinfa rct ion was 1.8 % at 30 days , 4.0 % at 1 year , and 6.9 % at 3 years . Definite stent thrombosis was responsible for 76.3 % of reinfa rct ions occurring within 30 days and 52.0 % of all reinfa rct ions within 3 years . Independent predictors of reinfa rct ion were current smoking , Killip class ≥2 , baseline thrombocytosis , multivessel disease , symptom onset-to-balloon time , and total stent length . R and omization to bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor and use of drug-eluting versus bare metal stents were not significant predictors of reinfa rct ion . Reinfa rct ion was a powerful independent predictor of subsequent cardiac mortality ( hazard ratio [ 95 % confidence interval]=7.65 [ 4.47–13.09 ] ; P<0.0001 ) and all-cause mortality ( hazard ratio [ 95 % confidence interval]=2.88 [ 1.74–4.78 ] ; P<0.0001 ) . Conclusions —Despite advances in pharmacotherapy and stents , reinfa rct ion after primary percutaneous coronary intervention is not infrequent , in the contemporary era is most often attributable to stent thrombosis , and is strongly associated with subsequent cardiac and all-cause mortality . Further enhancements in drugs and devices to prevent reinfa rct ion are needed to improve outcomes in high-risk patients with ST-segment – elevation myocardial infa rct ion . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00433966 OBJECTIVES --To assess the incidence and significance of anticardiolipin antibodies after myocardial infa rct ion and in unstable angina . DESIGN --A prospect i ve study of all patients under 60 admitted to the coronary care unit over a 12 month period with a diagnosis of acute myocardial infa rct ion who were followed up for a further 12 months . Patients admitted with unstable angina were similarly assessed but not followed up . Anticardiolipin antibody concentrations were compared with those of age matched controls . SETTING --A district general hospital . PATIENTS --307 patients with acute myocardial infa rct ion and 160 patients with unstable angina . RESULTS --Anticardiolipin antibody concentrations in the two patient groups did not differ significantly from those in the control groups . Antibody concentrations were not related to a history of angina or myocardial infa rct ion nor were they related to subsequent cardiovascular complications . CONCLUSION --This study shows no significant association between anticardiolipin antibody concentrations and either myocardial infa rct ion or unstable angina Antiphospholipid antibodies have been suggested as markers for a high risk of recurrent cardiovascular events in young survivors of an acute myocardial infa rct ion . However , there are few data to confirm or refute this hypothesis . In a cohort study , we have measured anticephalin ( aCEPHA ) and anticardiolipin ( aCL ) antibodies in a group of patients surviving an acute infa rct . Of 597 patients studied , 13.2 % were IgG or IgM aCEPHA positive compared with 4.4 % of a reference population ( n = 158 ; p = 0.002 ) . In a multivariate analysis , adjusted for major cardiovascular risk factors , neither aCEPHA ( IgG or IgM ) nor a CL ( IgG or IgM ) was an independent risk factor for mortality , reinfa rct ion , or non-haemorrhagic stroke . Although an increased proportion of survivors of a myocardial infa rct ion have antiphospholipid antibodies , the presence of such antibodies is not a risk factor for subsequent coronary or cerebrovascular thrombosis BACKGROUND Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis . Since factor Xa plays a central role in thrombosis , the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome . METHODS In this double-blind , placebo-controlled trial , we r and omly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months . The primary efficacy end point was a composite of death from cardiovascular causes , myocardial infa rct ion , or stroke . RESULTS Rivaroxaban significantly reduced the primary efficacy end point , as compared with placebo , with respective rates of 8.9 % and 10.7 % ( hazard ratio in the rivaroxaban group , 0.84 ; 95 % confidence interval [ CI ] , 0.74 to 0.96 ; P=0.008 ) , with significant improvement for both the twice-daily 2.5-mg dose ( 9.1 % vs. 10.7 % , P=0.02 ) and the twice-daily 5-mg dose ( 8.8 % vs. 10.7 % , P=0.03 ) . The twice-daily 2.5-mg dose of rivaroxaban reduced the rates of death from cardiovascular causes ( 2.7 % vs. 4.1 % , P=0.002 ) and from any cause ( 2.9 % vs. 4.5 % , P=0.002 ) , a survival benefit that was not seen with the twice-daily 5-mg dose . As compared with placebo , rivaroxaban increased the rates of major bleeding not related to coronary-artery bypass grafting ( 2.1 % vs. 0.6 % , P<0.001 ) and intracranial hemorrhage ( 0.6 % vs. 0.2 % , P=0.009 ) , without a significant increase in fatal bleeding ( 0.3 % vs. 0.2 % , P=0.66 ) or other adverse events . The twice-daily 2.5-mg dose result ed in fewer fatal bleeding events than the twice-daily 5-mg dose ( 0.1 % vs. 0.4 % , P=0.04 ) . CONCLUSIONS In patients with a recent acute coronary syndrome , rivaroxaban reduced the risk of the composite end point of death from cardiovascular causes , myocardial infa rct ion , or stroke . Rivaroxaban increased the risk of major bleeding and intracranial hemorrhage but not the risk of fatal bleeding . ( Funded by Johnson & Johnson and Bayer Healthcare ; ATLAS ACS 2-TIMI 51 Clinical Trials.gov number , NCT00809965 . ) CONTEXT The presence of antiphospholipid antibodies ( aPL ) has been associated with vascular occlusive events . However , the role of aPL in predicting ischemic events , particularly recurrent ischemic stroke , is controversial . OBJECTIVE To evaluate the effect of baseline aPL positivity ( ie , positivity for anticardiolipin antibodies [ aCL ] , lupus anticoagulant antibodies [ LA ] , or both ) on subsequent thrombo-occlusive events , including recurrent stroke . DESIGN , SETTING , AND PARTICIPANTS The Antiphospholipid Antibodies and Stroke Study ( APASS ) , a prospect i ve cohort study within the Warfarin vs Aspirin Recurrent Stroke Study ( WARSS ) , a r and omized double-blind trial ( N = 2206 ) conducted at multiple US clinical sites from June 1993 through June 2000 and comparing adjusted-dose warfarin ( target international normalized ratio , 1.4 - 2.8 ) and aspirin ( 325 mg/d ) for prevention of recurrent stroke or death . APASS participants were 1770 ( 80 % ) WARSS participants who consented to enroll in the APASS , with usable baseline blood sample s drawn prior to r and omization to the WARSS and analyzed for aPL status within 90 days of index stroke by a central independent laboratory . Quality assurance was performed on approximately 10 % of sample s by a second independent laboratory . MAIN OUTCOME MEASURE Two-year rate of the composite end point of death from any cause , ischemic stroke , transient ischemic attack , myocardial infa rct ion , deep vein thrombosis , pulmonary embolism , and other systemic thrombo-occlusive events . The primary analysis assessed the outcome associated with aPL positivity within each WARSS treatment group separately , after risk-factor adjustment ( since these aPL-positive vs aPL-negative comparisons were not r and omized ) . RESULTS Of the 1770 APASS patients , 720 ( 41 % ) were classified as aPL-positive and 1050 ( 59 % ) as aPL-negative . There was no increased risk of thrombo-occlusive events associated with baseline aPL status in patients treated with either warfarin ( relative risk [ RR ] , 0.99 ; 95 % confidence interval [ CI ] , 0.75 - 1.31 ; P = .94 ) , or aspirin ( RR , 0.94 ; 95 % CI , 0.70 - 1.28 ; P = .71 ) . The overall event rate was 22.2 % among aPL-positive and 21.8 % among aPL-negative patients . There was no treatment x aPL interaction ( P = .91 ) . Patients with baseline positivity for both LA and aCL antibodies tended to have a higher event rate ( 31.7 % ) than did patients who tested negative for both antibodies ( 24.0 % ) ( unadjusted RR , 1.36 ; 95 % CI , 0.97 - 1.92 ; P = .07 ) . Classification and regression tree analyses did not identify a specific LA test or aCL isotype or titer that was associated with increased risk of thrombo-occlusive event . CONCLUSIONS The presence of aPL ( either LA or aCL ) among patients with ischemic stroke does not predict either increased risk for subsequent vascular occlusive events over 2 years or a differential response to aspirin or warfarin therapy . Routine screening for aPL in patients with ischemic stroke does not appear warranted To date very few studies that analyze the prevalence of anticardiolipin antibodies ( ACA ) in healthy subjects have been reported . No data based on a systematic analysis of normal subjects with positive ACA is available . The aim of the present study was to evaluate the prevalence of ACA ; its clinical significance and relationship to the lupus anticoagulant ( LA ) and other autoimmune parameters in an apparently healthy population . 552 normal blood donors from a blood bank were r and omly selected . ACA positive donors who consented were monitored over a period of twelve months and tested every three months . ACA ( IgG and IgM isotypes ) were quantitated by enzyme linked immunoassay ( ELISA ) . The prevalence for IgG ACA in our donor population was estimated to be 6.5 % , and 9.4 % for IgM ACA , which is similar to the one previously reported for IgG and slightly higher for IgM. It is worth noting that in our study ACA positive donors exhibited a progressive negativization . Eight donors with IgG ACA and seven with IgM ACA remained positive for nine months . Five donors with IgG ACA and four with IgM ACA had family history of thromboembolic disease . One donor with IgG ACA and two with IgM ACA had had unexplained miscarriages in the past . We did not find any relationship between ACA and LA , nor between ACA positivity and the clinical and laboratory data studied . Pseudopositivity for lues was not found . No thrombotic event occurred in donors that were positive for ACA during the 12-month follow-up PURPOSE To examine the prevalence of anticardiolipin antibodies ( ACLA ) in relatively young patients with acute myocardial infa rct ion ( MI ) and their role in subsequent coronary and thromboembolic events in the post-MI period . PATIENTS AND METHODS In 124 relatively young survivors ( aged 65 or younger ) of acute MI , ACLA were measured in a controlled prospect i ve study on admission and 3 months later . Myocardial reinfa rct ion and thromboembolic events during a mean follow-up period of 19 + /- 3 months were diagnosed by st and ard tests . RESULTS Seventeen ( 14 % ) of the 124 patients were ACLA positive ( either IgM or IgG ) upon admission compared with 2 out of 76 ( 3 % ) of the control group matched for age and coronary risk factors ( P < 0.01 ) . The levels of ACLA remained unchanged in all but 1 patient 3 months later . During the follow-up period the rate of thromboembolic events and myocardial reinfa rct ion was significantly higher in the ACLA-positive patients as compared with the ACLA-negative group : 41 % versus 4 % ( P < 0.0001 ) and 35 % versus 10 % ( P < 0.05 ) , respectively . Using logistic regression , high titer of ACLA was found to be the only independent risk factor for subsequent thromboembolic events or myocardial reinfa rct ion after acute MI . CONCLUSIONS High prevalence of ACLA was found in relatively young survivors of acute MI . The presence of ACLA is a marker for increased risk of subsequent myocardial reinfa rct ion and thromboembolic events after acute MI Objectives To assess the prevalence of the main causes of morbi-mortality in the antiphospholipid syndrome ( APS ) during a 10-year-follow-up period and to compare the frequency of early manifestations with those that appeared later . Methods In 1999 , we started an observational study of 1000 APS patients from 13 European countries . All had medical histories documented when entered into the study and were followed prospect ively during the ensuing 10 years . Results 53.1 % of the patients had primary APS , 36.2 % had APS associated with systemic lupus erythematosus and 10.7 % APS associated with other diseases . Thrombotic events appeared in 166 ( 16.6 % ) patients during the first 5-year period and in 115 ( 14.4 % ) during the second 5-year period . The most common events were strokes , transient ischaemic attacks , deep vein thromboses and pulmonary embolism . 127 ( 15.5 % ) women became pregnant ( 188 pregnancies ) and 72.9 % of pregnancies succeeded in having one or more live births . The most common obstetric complication was early pregnancy loss ( 16.5 % of the pregnancies ) . Intrauterine growth restriction ( 26.3 % of the total live births ) and prematurity ( 48.2 % ) were the most frequent fetal morbidities . 93 ( 9.3 % ) patients died and the most frequent causes of death were severe thrombosis ( 36.5 % ) and infections ( 26.9 % ) . Nine ( 0.9 % ) cases of catastrophic APS occurred and 5 ( 55.6 % ) of them died . The survival probability at 10 years was 90.7 % . Conclusions Patients with APS still develop significant morbidity and mortality despite current treatment . It is imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent these complications Objectives The long-term prognosis of individuals fulfilling the laboratory criteria , but not clinical criteria , of antiphospholipid syndrome ( APS ) has not been widely investigated . The primary aim of this study was to evaluate the incidence of first thrombotic event ( deep venous thrombosis ( DVT ) , pulmonary embolism ( PE ) , myocardial infa rct ion ( MI ) , stroke or transient ischaemic attack ( TIA ) in a nationwide antiphospholipid antibody ( aPL ) carrier cohort . Design We conducted a prospect i ve nationwide cohort study . Setting The aPL profile of participants was recorded from the laboratory data base . Information was collected about thrombotic and pregnancy complications , subsequent medical history , other risk factors for thrombosis , use of prophylactic antithrombotic medication and general health . Participants Participants included adult asymptomatic aPL carriers recognized in Finl and during 1971–2009 . Main outcome measure The main outcome measure was incidence of first thrombotic event . Results A total of 119 ( 89 % female ) aPL carriers were followed for mean ( SD ) of 9.1 ( 7.5 ) years ( range 3–41 years ) . Sixty-one per cent of the study participants had autoimmune disease , most often systemic lupus erythematosus ( SLE ) . Thirty-six of 119 ( 30 % ) were either double or triple positive , 56 % single lupus anticoagulant ( LA ) positive , and 8 % and 5 % single anticardiolipin antibodies ( aCL ) and anti-β2glycoprotein I antibodies ( aβ2GPI ) positive , respectively . Nine ( 7.6 % ) study patients experienced a first thrombotic event ( five DVT , one PE , two MI , one TIA ) mean ( SD ) 7.2 ( 8.3 ) years ( range 1–26 years ) after aPL detection ( annual incidence rate 0.8 % ) . All individuals who developed thrombotic complications had autoimmune disease . Annual rate of first thrombotic event in carriers of single positivity ( 0.65 % ) was equal to the known risk of thrombosis in the healthy Caucasian population , whereas the rate was two times higher in carriers of double or triple positivity ( 1.27 % ) . Sixteen of 79 ( 20 % ) women experienced pregnancy complications . Conclusions Double or triple positivity for aPL is a risk factor for future thrombotic events , especially in individuals with an underlying autoimmune disease , whereas single positivity does not seem to carry an elevated risk of thrombosis |
793 | 25,222,468 | None of the studies definitively blinded participants .Rapid viral testing result ed in a trend toward decreased antibiotic use in the ED , but this was not statistically significant .
There is insufficient evidence to support routine rapid viral testing to reduce antibiotic use in pediatric EDs .
However , rapid viral testing does reduce the rate of chest X-rays in the ED . | BACKGROUND Pediatric acute respiratory infections ( ARIs ) represent a significant burden on pediatric Emergency Departments ( EDs ) and families .
Most of these illnesses are due to viruses .
However , investigations ( radiography , blood , and urine testing ) to rule out bacterial infections and antibiotics are often ordered because of diagnostic uncertainties .
This results in prolonged ED visits and unnecessary antibiotic use .
The risk of concurrent bacterial infection has been reported to be negligible in children over three months of age with a confirmed viral infection .
Rapid viral testing in the ED may alleviate the need for pre caution ary testing and antibiotic use .
OBJECTIVES To determine if the use of a rapid viral detection test for children with an acute respiratory infection ( ARI ) in Emergency Departments ( EDs ) changes patient management and re source use in the ED , compared to not using a rapid viral detection test .
We hypothesized that rapid viral testing reduces antibiotic use in the ED as well as reduces the rate of ancillary testing and length of ED visits . | Managing children with influenza-like illness is associated with costly and painful interventions because , in order to distinguish viral from bacterial infections , diagnostic tests ( including routine blood examinations and chest radiographs ) are frequently performed,1,2 and the empirical use of antimicrobial agents is common.3 Various rapid diagnostic techniques for the detection of influenza viruses have been developed , but few data are available on their impact on child care.2,4,5 The aim of this study was to assess the effect of a rapid diagnosis of influenza infection on the management of children with influenza-like illness in an emergency department . All patients seen for influenza-like illness from 6 January to 27 February 2002 , at the paediatric emergency department of the University of Milan , Italy , were enrolled and blindly r and omly assigned in a 1:1 ratio to undergo a rapid test for the detection of influenza viruses or no rapid test . Influenza-like illness was defined as an axillary temperature of ⩾37.8 ° C and at least one symptom of acute upper or lower respiratory tract disease.6 The patients who underwent the test had their throats swabbed after vigorously rubbing both tonsillar surfaces and the posterior pharynx ; the swab was then immediately su bmi tted to the Quickvue influenza test ( Quidel , Milan , Italy ) for the rapid detection of influenza A and B viruses . The test , which has an overall sensitivity of 74–95 % and an overall specificity of 76–98%,5,7,8 was performed by a postgraduate student in accordance with the manufacturer ’s recommendations . The results were available after 10 Recent empirical evidence supports the importance of adequate r and omization in controlled trials . Trials with inadequate allocation concealment have been associated with larger treatment effects compared with trials in which authors reported adequate allocation concealment . While that provides empirical evidence of bias being interjected into trials , trial investigators rarely document the sensitive details of subverting the intended purpose of r and omization . This article relates anonymous accounts run the gamut from simple to intricate operations , from transillumination of envelopes to search ing for code in the office files of the principal investigator . They indicate that deciphering is something more frequent than a rate occurrence . These accounts prompt some method ological recommendations to help prevent deciphering . R and omized controlled trials appear to annoy human nature -- if properly conducted , indeed they should OBJECTIVE To determine the impact of the rapid diagnosis of influenza on physician decision-making and patient management , including laboratory tests and radiographs ordered , patient charges associated with these tests , antibiotics/antivirals prescribed , and length of time to patient discharge from the emergency department . METHODS Patients aged 2 months to 21 years presenting to an urban children 's teaching hospital emergency department were screened for fever and cough , coryza , myalgias , headache , and /or malaise . After obtaining informed consent , patients were r and omized to 1 of 2 groups : 1 ) physician receives ( physician aware of ) the rapid influenza test result ; or 2 ) physician does not receive ( physician unaware of ) the result . For patients in the physician aware group , nasopharyngeal swabs were obtained , immediately tested with the FluOIA test for influenza A and B , and the result was placed on the chart before patient evaluation by the attending physician . For the physician unaware group , nasopharyngeal swabs were obtained , stored according to manufacturer 's directions , and tested within 24 hours . Results for the physician unaware group were not disclosed to the treating physicians at any time . The 2 result ant influenza-positive groups ( aware and unaware ) were compared for laboratory and radiograph studies and their associated patient charges , antibiotic/antiviral prescriptions , and length of stay in the emergency department . RESULTS A total of 418 patients were enrolled , and 391 completed the study . Of these , 202 tested positive for influenza . Comparison of the 96 influenza-positive patients whose physician was aware of the result with the 106 influenza-positive patients whose physician was unaware of the result revealed significant reductions among the former group in : 1 ) numbers of complete blood counts , blood cultures , urinalyses , urine cultures , and chest radiographs performed ; 2 ) charges associated with these tests ; 3 ) antibiotics prescribed ; and 4 ) length of stay in the emergency department . The number of influenza-positive patients who received prescriptions for antiviral drugs was significantly higher among those whose physician was aware of the result . CONCLUSIONS Physician awareness of a rapid diagnosis of influenza in the pediatric emergency department significantly reduced the number of laboratory tests and radiographs ordered and their associated charges , decreased antibiotic use , increased antiviral use , and decreased length of time to discharge OBJECTIVES Acute respiratory tract infections represent a significant burden on pediatric emergency departments ( ED ) and families . We hypothesized that early and rapid diagnosis of a viral infection alleviates the need for ancillary testing and antibiotic treatment . STUDY DESIGN We conducted a r and omized , controlled trial of children 3 to 36 months of age with febrile acute respiratory tract infections at a pediatric ED . Two hundred four subjects were r and omly assigned to receive rapid respiratory viral testing on admission or a routine ED admission protocol . Outcome measures were : mean length of visits , rate of ancillary tests , and antibiotic prescription in the ED . A follow-up call was made to all study subjects to inquire about further healthcare visits , ancillary testing , and antibiotic prescription after ED discharge . RESULTS We did not find a statistically significant difference in ED length of visits , rate of ancillary testing , or antibiotic prescription rate in the ED between the study groups . There was , however , a significant reduction in antibiotic prescription after ED discharge ( in the group who had rapid viral testing RR = 0.36 ; 95 % CI = 0.14 , 0.95 ) . CONCLUSIONS Rapid multi-viral testing in the ED did not significantly affect ED patient treatment but may reduce antibiotic prescription in the community after discharge from the ED , suggesting a novel strategy to alter community physician antibiotic prescription patterns BACKGROUND Evidence shows that the rapid detection of influenza using an enzyme-linked immunosorbent assay decreases antibiotic use in the treatment of pediatric patients . To our knowledge , the effect on other diagnostic testing in an emergency department ( ED ) has not been examined . OBJECTIVE To determine the effect of rapid diagnosis of influenza virus type A on the clinical management of febrile infants and toddlers in a pediatric ED at an urban children 's hospital . MATERIAL S AND METHODS A retrospective review of ED records from an electronic data base was performed . All children 2 to 24 months of age , with a temperature higher than 39 degrees C who had a positive influenza virus type A test result using an enzyme-linked immunosorbent assay from November 1 , 1998 , through April 30 , 2000 ( n = 72 ) , were included in this study . Two groups were compared-those who had positive test results reported before discharge from the ED ( early diagnosis ) and those who had positive test results after discharge ( late diagnosis ) . RESULTS Forty-seven patients ( 65 % ) were in the early diagnosis group and 25 ( 35 % ) in the late diagnosis group . The groups were similar for age , temperature , and triage category . Fewer patients in the early diagnosis group received ceftriaxone sodium compared with those in the late diagnosis group ( 2 % vs 24 % , P = .006 ) ; there were fewer urinalyses ( 2 % vs 24 % , P = .006 ) and complete blood cell counts performed ( 17 % vs 44 % , P = .02 ) . CONCLUSIONS Rapid confirmation of influenza virus type A infection seems to decrease ancillary tests and antibiotic use in febrile infants and toddlers in the ED . A prospect i ve study with a larger group is needed to confirm these findings BACKGROUND The evaluation of young febrile infants is controversial , in part because it is unclear whether clinical evidence of a viral infection significantly reduces the risk of serious bacterial infections ( SBIs ) . Specifically , it remains unclear whether the risk of SBI is altered in a meaningful way in the presence of respiratory syncytial virus ( RSV ) infections . OBJECTIVE The objective of this study was to determine the risk of SBI in young febrile infants who are infected with RSV compared with those without RSV infections . METHODS We conducted a 3-year multicenter , prospect i ve , cross-sectional study . All febrile ( > or = 38 degrees C ) infants who were < or = 60 days of age and presented to any of 8 pediatric emergency departments from October through March 1998 - 2001 were eligible . General clinical appearance was evaluated using the Yale Observational Scale . We determined RSV status by antigen testing of nasopharyngeal secretions . We defined bronchiolitis as either wheezing alone or chest retractions in association with an upper respiratory infection . We evaluated infants with blood , urine , cerebrospinal fluid , and stool cultures . Urinary tract infection ( UTI ) was defined by single pathogen growth of > or = 5 x 10(4 ) cfu/mL , or > or = 10(4 ) cfu/mL in association with a positive urinalysis in a catheterized specimen , or > or = 10(3 ) cfu/mL in a suprapubic aspirate . Bacteremia , bacterial meningitis , and bacterial enteritis were defined by growth of a known bacterial pathogen . SBI was defined as any of the above-mentioned 4 bacterial infections . RESULTS We enrolled 1248 patients , including 269 ( 22 % ) with RSV infections . The overall SBI status could be determined in 1169 ( 94 % ) of the 1248 patients , and the rate of SBIs was 11.4 % ( 133 of 1169 ; 95 % confidence interval [ CI ] : 9.6%-13.3 % ) . The rate of SBIs in the RSV-positive infants was 7.0 % ( 17 of 244 ; 95 % CI : 4.1%-10.9 % ) compared with 12.5 % ( 116 of 925 ; 95 % CI : 10.5%-14.8 % ) in the RSV-negative infants ( risk difference : 5.5 % ; 95 % CI : 1.7%-9.4 % ) . The rate of UTI in the RSV-positive infants was 5.4 % ( 14 of 261 ; 95 % CI : 3.0%-8.8 % ) compared with 10.1 % ( 98 of 966 ; 95 % CI : 8.3%-12.2 % ) in the RSV-negative infants ( risk difference : 4.7 % ; 95 % CI : 1.4%-8.1 % ) . The RSV-positive infants had a lower rate of bacteremia than the RSV-negative infants ( 1.1 % vs 2.3 % ; risk difference : 1.2 % ; 95 % CI : -0.4 % to 2.7 % ) . No RSV-positive infant had bacterial meningitis ( 0 of 251 ; 95 % CI : 0%-1.2 % ) ; however , the differences between the 2 groups with regard to bacteremia and bacterial meningitis did not achieve statistical significance . CONCLUSIONS Febrile infants who are < or = 60 days of age and have RSV infections are at significantly lower risk of SBI than febrile infants without RSV infection . Nevertheless , the rate of SBIs , particularly as a result of UTI , remains appreciable in febrile RSV-positive infants OBJECTIVES To determine the effect of point-of-care testing ( POCT ) for influenza on the physician management of febrile children who are at risk for serious bacterial illness ( SBI ) on the basis of age and temperature and who are presenting to a pediatric emergency department ( ED ) during an influenza outbreak . METHODS Patients 2 - 3 months of age with temperature of > or = 38 degrees C and patients 3 - 24 months of age with temperature of > or = 39 degrees C who were presenting to a pediatric ED during an influenza outbreak were enrolled into a prospect i ve , quasi-r and omized , controlled trial . Influenza testing was performed on enrolled patients by either the POCT or the st and ard-testing ( ST ) methods . The two groups were compared in terms of laboratory testing , chest radiography , antibiotic use , visit-associated costs , pediatric ED lengths of stay , inpatient admission , and return visits to the pediatric ED . Similar analyses also were performed on the result ing subgroups of patients on the basis of method of testing ( POCT or ST ) and test result ( positive or negative ) . RESULTS Of 767 eligible patients , 700 ( 91 % ) completed the study . No significant differences were demonstrated between the POCT and ST groups with respect to laboratory tests ordered , chest radiographs obtained , antibiotic administration , inpatient admission , return visits to the pediatric ED , lengths of stay , or visit-associated costs . In the subgroup analysis , the adjusted odds ratios ( ORs ) for blood culture in influenza test-positive to -negative patients were 0.59 and 0.71 in the POCT and ST groups , respectively ( p = 0.088 ) . The adjusted ORs for urine culture in influenza test-positive to -negative patients were 0.46 and 0.67 in the POCT and ST groups , respectively ( p = 0.005 ) . CONCLUSIONS When using a strategy of performing influenza testing on all patients at risk for SBI who presented to a pediatric ED during an influenza outbreak , the method of testing ( POCT or ST ) did not appear to significantly alter physician management , cost , or length of stay in the pediatric ED . However , if the interaction of the method of testing and the test result ( positive or negative ) were considered , a positive POCT for influenza was associated with a significant reduction in orders for urinalyses and urine cultures Background . Few studies have examined the impact of rapid viral diagnostic tests on patient management . Objective . To assess the effect of rapid diagnosis of influenza A infections on patient management . Methods . The medical records of children with respiratory infections who were evaluated at a children 's hospital between July 1 , 1995 , and June 30 , 1997 , were review ed . Children ( n = 56 ) evaluated in the Emergency Department ( ED ) who had a positive influenza A enzyme immunoassay ( EIA ) were compared with two control groups for the likelihood of admission , antibiotic use and duration of hospitalization and antibiotic administration . Results . Patients discharged from the ED with a positive EIA test were less likely to receive antibiotics than those with a negative EIA test ( 20%vs . 53%;P = 0.04 ) . Patients admitted to the hospital with a positive EIA test were as likely to receive antibiotics as those without a rapid diagnosis , but the duration of antibiotic administration was significantly shorter in the group with a positive EIA test ( 3.5 vs. 5.4 days;P = 0.03 ) . Patients with a positive EIA test also were more likely to receive antiviral therapy than either control group ( 25%vs . 0 and 1.8%;P < 0.001 ) . Conclusions . The detection of influenza A by EIA has a positive impact on medical management by decreasing antibiotic use in pediatric patients evaluated in an ED , by decreasing the duration of antibiotic use in hospitalized patients and by encouraging antiviral therapy OBJECTIVE To determine whether a point-of-care rapid influenza test impacts the diagnostic evaluation and treatment of children with acute respiratory illnesses . DESIGN R and omized controlled trial . SETTING Pediatric emergency department and acute care clinic of a children 's hospital . PARTICIPANTS Children aged younger than 5 years with fever or acute respiratory symptoms during 2 influenza seasons ( 2002 through 2004 ) . INTERVENTIONS Surveillance days were r and omized to performance or no performance of a point-of-care rapid influenza test . All children had a nasal and throat swab obtained for laboratory tests . The rapid test group had another nasal swab obtained for the QuickVue Influenza Test ( Quidel Corp , San Diego , Calif ) , which was performed by nurses ; results were shared immediately with treating physicians . MAIN OUTCOME MEASURES Rapid test results were compared with results of the viral culture or 2 polymerase chain reaction assays for influenza . Diagnostic test ordering and antibiotic prescribing were compared for the groups . RESULTS Of 468 enrolled children , 306 were from the emergency department and 162 from the clinic . Overall , 88 children ( 19 % ) had influenza infection . Of 205 children in the rapid test group , 51 ( 25 % ) had influenza infection . The rapid influenza test was 82 % sensitive and 99 % specific . In the emergency department , fewer children in the rapid test group had diagnostic tests ordered than in the no rapid test group ( 39 % vs 51 % , P = .03 ) . There was no difference in test ordering in the clinic or in antibiotic prescribing in either setting . The use of antivirals was low . CONCLUSIONS Point-of-care rapid influenza tests were sensitive and specific and were associated with less diagnostic testing in the emergency department |
794 | 24,951,297 | While not mutually exclusive , the primary mechanism(s ) for performance enhancement likely differs depending on the duration of the exercise .
In short duration exercise situations ( ∼1 h ) , oral receptor exposure to CHO , via either mouthwash or oral consumption ( with enough oral contact time ) , which then stimulates the pleasure and reward centers of the brain , provide a central nervous system-based mechanism for enhanced performance .
Thus , the type and ( or ) amount of CHO and its ability to be absorbed and oxidized appear completely irrelevant to enhancing performance in short duration exercise situations .
For longer duration exercise ( > 2 h ) , where muscle glycogen stores are stressed , the primary mechanism by which carbohydrate supplementation enhances performance is via high rates of CHO delivery ( > 90 g/h ) , result ing in high rates of CHO oxidation . | null | null |
795 | 25,088,685 | Discontinuation secondary to adverse events was more common in patients on mTORi , whereas the incidence of skin cancers and cytomegalovirus infection was lower in patients on mTORi . | null | null |
796 | 17,162,986 | RESULTS Psychological and behavioral therapies produced reliable changes in several sleep parameters of individuals with either primary insomnia or insomnia associated with medical and psychiatric disorders .
DISCUSSION These up date d findings provide additional evidence in support of the original review 's conclusions as to the efficacy and generalizability of psychological and behavioral therapies for persistent insomnia . | BACKGROUND Recognition that psychological and behavioral factors play an important role in insomnia has led to increased interest in therapies targeting these factors .
A review paper published in 1999 summarized the evidence regarding the efficacy of psychological and behavioral treatments for persistent insomnia .
The present review provides an up date of the evidence published since the original paper .
As with the original paper , this review was conducted by a task force commissioned by the American Academy of Sleep Medicine in order to up date its practice parameters on psychological and behavioral therapies for insomnia . | This study explores the usefulness of relaxation and gradual medication withdrawal in weaning insomniacs from sleep ( hypnotic ) medication . We recruited 40 volunteers from the community who had insomnia , half of whom were chronic users of hypnotics while the other half were nonmedicated . Half of all participants ( 10 medicated and 10 nonmedicated ) received progressive relaxation . All medicated participants received a st and ard gradual drug withdrawal program . Medicated participants reduced sleep medication consumption by nearly 80 % . Participants who received relaxation obtained additional benefits in sleep efficiency , rated quality of sleep , and reduced withdrawal symptoms . Medicated and nonmedicated participants attained comparable , improved sleep by posttreatment and follow-up . Hypnotic withdrawalwas accompanied by serious worsening of insomnia , but this dissipated by the end of the withdrawal period . The psychological treatment of hypnotic-dependent insomnia has high potential for making an important clinical contribution Forty-five adults with primary insomnia received cognitive-behavioral therapy ( CBT ) implemented in a group therapy format , in individual face-to-face therapy or through brief individual telephone consultations . The results indicate that CBT was effective in improving sleep parameters with all 3 methods of treatment implementation , and there was no significant difference across methods of implementation . All 3 treatment modalities produced improvements in sleep that were maintained for 6 months after treatment completion . These results suggest that group therapy and telephone consultations represent cost-effective alternatives to individual therapy for the management of insomnia Patients with primary insomnia overestimate their sleep onset latency ( SOL ) and underestimate their total sleep time ( TST ) . The present study aim ed to test the utility of a novel behavioural experiment design ed to correct distorted perception of sleep among patients diagnosed with primary insomnia . Individuals with primary insomnia were asked to wear an actigraph and keep a sleep diary for three nights . On the following day , half were shown the discrepancy between the data recorded on the actigraph and their sleep diary ( Shown-Discrepancy Group ) , the other half were not shown the discrepancy ( No-Demonstration Group ) . Participants were then asked to wear the actigraph and keep a sleep diary for three further nights . Following the behavioural experiment , the Shown-Discrepancy Group estimated their SOL more accurately and reported less anxiety and preoccupation about sleep compared to the No-Demonstration Group . The theoretical and clinical implication s of these findings are discussed Objective : To compare treatment outcomes associated with combined pharmacologic and non-pharmacologic treatments for psychophysiological insomnia . Background : Treatments for insomnia have included a variety of pharmacotherapy and cognitive-behavioral interventions , although few studies have investigated the combined efficacy of drug and non-drug therapy . Methods : Forty-one patients with primary insomnia were r and omly assigned to one of three treatment groups : ( i ) estazolam + muscle relaxation , ( ii ) estazolam + guided imagery , and ( iii ) estazolam + sleep education . After 4 weeks of active treatment , subjects were withdrawn from medication and followed for an additional 6 months . Results : Significant improvements were observed in self-report measures of total sleep time , sleep efficiency , and wakefulness after sleep onset in the combined drug and relaxation groups , compared to a significant improvement in total sleep time only in the educational control group . At follow-up , all three groups showed significant improvements across the major sleep measures . Positive changes were also observed in quality of life measures , including mood state and self- ratings of daytime arousal . Conclusions : These findings provide support for the value of combined pharmacotherapy and relaxation training in the treatment of psychophysiological insomnia Previous research suggests that self-defined insomniacs are distinguished from normals by high levels of anxiety and physiological arousal , which might be mitigated by muscle relaxation . This study assessed the relative effects of frontal EMG biofeedback , progressive relaxation , and a placebo set of “ relaxation ” exercises on the sleep of 18 onset insomniacs . Each subject was trained in one of these three methods for six half-hour sessions and slept in the laboratory for two consecutive nights before and after training . The experimental groups demonstrated significant decreases in physiological activity during training while changes in the control group were minimal . Reductions in sleep-onset time were : biofeedback group , 29.66 minutes ; progressive relaxation group , 22.92 minutes ; control group , 2.79 minutes . The experimental groups improved significantly(p<.05 ) more than the control group , but did not differ from each other . No significant relationships between physiological levels and sleep-onset time were found , which suggests that muscle relaxation alone was not responsible for subjects ' improvements . Since 20 minutes of daily practice were required to achieve an approximate 30-minute decrease in sleep-onset time , the practical utility of the methods is question ed Older adults with comorbid insomnia and medical illness have been excluded from behavioral treatment research , but recent evidence suggested that such treatments would be effective with this population . In this study , 38 older adults with comorbid insomnia were r and omized to 1 of 3 conditions : classroom cognitive-behavioral treatment ( CBT ) , home-based audio relaxation treatment ( HART ) , or delayed-treatment control . Compared to the control group , the CBT group had significant changes in 5 of 7 self-report measures of sleep at the 4-month follow-up . The HART group obtained significant outcomes on 3 of 7 measures . Wrist actigraphy measures and secondary - outcome measures did not yield significant findings for either treatment . Clinical ly significant changes at follow-up were obtained for 54 % of patients in CBT , 35 % in HART , and 6 % in the control group when treatment dropouts were included . Although not as effective as in-person CBT , home interventions may have utility as a first-line , low-cost treatment To assess the effect of progressive relaxation training on insomnia in institutionalised chronic alcoholic men , 22 subjects between the ages of 20 and 60 years , were r and omly allocated to treatment and control groups . The treatment group received 10 sessions of progressive relaxation training over a 2-wk . period after which both groups completed a postexperimental question naire . Analysis showed a significant improvement in the sleeping patterns of the treated group , but no changes in the sleeping patterns of the control group . In addition , a distribution-free two- sample permutation test to compare mean differences of the groups confirmed that a significantly greater change occurred in the quality of the sleeping patterns of the treated group This investigation compared progressive muscle relaxation plus cognitive distraction ( PMR/CD ) , hypothesized to better improve sleep onset , versus sleep restriction and stimulus control ( SR/SC ) , hypothesized to better improve sleep maintenance , versus a flurazepam ( Dalmane ) positive contrast condition ( MED ) and a sleep hygiene education minimal treatment control condition ( SHE ) . Participants with chronic insomnia ( N = 53 ) , completed 2 baseline weeks of sleep diaries , and were r and omly assigned to a treatment group for 2 more weeks . In the second phase , PMR/CD participants were assigned to 2 weeks of PMR/CD + SR/SC + SHE while SHE participants continued SHE . Results indicated that PMR/CD had greater effect upon sleep onset than SR/SC and SHE , SR/SC had greater effect on sleep maintenance than PMR/CD , and MED was better than the other treatments . In the second phase , the treatment package produced modest additional improvements and SHE performed superior to expectations OBJECTIVE The question addressed here is : Can a discrete sleep disordered breathing ( SDB ) play a role in the insomnia complaint of postmenopausal chronic insomniacs ? To respond to the query , two groups of individuals derived from a cohort of postmenopausal chronic insomniacs recruited mostly from the community were enlisted in a treatment protocol . These subjects were all individuals identified with normal breathing ( n=68 ) and all those recognized with Upper Airway Resistance Syndrome ( UARS ) ( n=62 ) pooled from a cohort of 349 postmenopausal insomniacs . TREATMENT PROTOCOL The 62 UARS were allocated to either treatment of chronic insomnia by behavioral approaches or treatment of SDB . Based on ENT evaluation , health professionals in charge of patients selected either treatment with nasal CPAP or treatment of nasal turbinates . A stratification correction was performed to obtain a near equal number of both treatment modalities in each of the two subgroups . The 68 individuals with normal breathing were r and omly allocated to immediate behavioral treatment of insomnia or delay treatment of insomnia . The delay treatment received a list of 10 sleep hygiene recommendations by mail . METHODOLOGY Question naires , visual analog scales ( VAS ) , Epworth Sleepiness Scale ( ESS ) , clinical interviews , clinical evaluation with oto-laryngologic clinical assessment of a presence/absence of narrow upper airway and location of narrowing . Actigraphy and polysomnography ( PSG ) with pressure transducer/ and nasal cannula system and esophageal manometry . DATA ANALYSES All recording data were scored blind to patient 's condition . RESULTS Two subjects in the SBD-CPAP treated group ( Group B ) and two subjects in the delayed treatment group ( Group D ) dropped out . Total sleep time was improved compared to baseline in all groups , including the delayed treatment group . One group was significantly better ( ANOVA , P=.05 ) with a more important delta score compared to baseline , and this was the behaviorally treated non-SDB . Sleep latency was significantly decreased in the behaviorally treated group ( with or without SBD ) , P=.05 , compared to SBD-treated and delayed treatment groups . Sleep latency was , however , improved in all groups . VAS for " quality of sleep " was higher at 6 months in all the groups when compared to " baseline " values . VAS for " daytime fatigue " showed significant differences among the four groups ( ANOVA , P=.01 ) ; the overall score at the end of treatment was significantly better in the SDB-treated group than the other three groups . SBD was treated either by radio frequency on nasal turbinate or by nasal CPAP . CPAP-treated patients had a lower VAS score than nasal turbinate treatment , but the difference was only a trend . The delta improvement ( 6-month baseline condition ) in " daytime fatigue " of each subgroup was calculated and compared within and between groups . Despite the small number of subjects , the turbinate-treated subgroup was significantly different from Groups B , C and D ( ANOVA , P=.05 ) . When a similar comparison was made with the nasal CPAP group , there was only a nonsignificant trend when compared to Groups B , C and D. CONCLUSION Abnormal breathing during sleep significantly enhanced complaints of daytime fatigue in postmenopausal chronic insomniacs and this complaint improved with SDB treatment . This improvement is significantly better compared to SDB insomniacs treated with a behavioral regimen . Behavioral treatment , however , gave the best response in the non-SDB chronic insomnia group and improved better long sleep latency even in the SDB group . These results suggest the need to find an appropriate treatment for SBD even if mild and to recognize the role of SDB in relation to symptoms seen with chronic insomnia OBJECTIVE To evaluate the clinical and cost impact of providing cognitive behaviour therapy ( CBT ) for insomnia ( comprising sleep hygiene , stimulus control , relaxation and cognitive therapy components ) to long-term hypnotic drug users in general practice . DESIGN A pragmatic r and omised controlled trial with two treatment arms ( a CBT treated ' sleep clinic ' group , and a ' no additional treatment ' control group ) , with post-treatment assessment s commencing at 3 and 6 months . SETTING Twenty-three general practice s in Sheffield , UK . PARTICIPANTS Two hundred and nine serially referred patients aged 31 - 92 years with chronic sleep problems who had been using hypnotic drugs for at least 1 month ( mean duration = 13.4 years ) . RESULTS At 3- and 6-month follow-ups patients treated with CBT reported significant reductions in sleep latency , significant improvements in sleep efficiency , and significant reductions in the frequency of hypnotic drug use ( all P<0.01 ) . Among CBT treated patients SF-36 scores showed significant improvements in vitality at 3 months ( P<0.01 ) . Older age presented no barrier to successful treatment outcomes . The total cost of service provision was 154.40 per patient , with a mean incremental cost per quality -adjusted life-year of 3416 ( at 6 months ) . However , there was evidence of longer term cost offsets owing to reductions in sleeping tablet use and reduced utilisation of primary care services . CONCLUSIONS In routine general practice setting s , psychological treatments for insomnia can improve sleep quality and reduce hypnotic consumption at a favourable cost among long-term hypnotic users with chronic sleep difficulties Psychological treatment of insomnia has focused on primary insomnia ( i.e. , having a psychological origin ) . Secondary insomnia , sleep disturbance caused by a psychiatric or medical disorder , although it is more common than primary insomnia , has received very little attention as a result of the belief that it would be refractory to treatment . The present study r and omly assigned older adults with secondary insomnia to a treatment group , 4 sessions composed of relaxation and stimulus control , or a no-treatment control group . Self-report assessment s conducted at pretreatment , posttreatment , and a 3-month follow-up revealed that treated participants showed significantly greater improvement on wake time during the night , sleep efficiency percentage , and sleep quality rating . The authors hypothesize that treatment success was probably due in part to difficulty in diagnostic discrimination between primary and secondary insomnia There is substantial experimental evidence that behavioral treatment of insomnia produces significant clinical improvement and that treatment gains tend to be maintained over time . Less clear is whether behavioral treatment is effective as it is plied in clinical setting s. In this clinical case series study , we evaluated 47 patients with primary insomnia . It was found that patients were , on average , 43 % improved . This average corresponded to a 65 % reduction in sleep latency , a 46 % decrease in number of awakenings per night , a 48 % reduction in wake time after sleep onset , and a 13 % increase in total sleep time . These results suggest that behavioral treatment for insomnia is as effective in clinical setting s as it is as under clinical trial conditions Insomniacs commonly complain that they are unable to get to sleep at night due to unwanted thoughts , worries and concerns . The present study investigated whether brief training in identifying and elaborating an interesting and engaging imagery task for use during the pre-sleep period can reduce unwanted pre-sleep cognitive activity and sleep onset latency . Forty one people with insomnia were given one of three instructional sets to follow on the experimental night ; instructions to distract using imagery , general instructions to distract , or no instructions . Based on previous findings reported by Salkovskis & Campbell ( 1994 ) ' Behaviour Research and Therapy 32 ( 1994 ) 1 ' and ironic control theory ( Wegner , 1994 ) ' Psychological Review 101 ( 1994 ) 34 ' , it was predicted that ( 1 ) " imagery distraction " would be associated with shorter sleep onset latency and less frequent and distressing pre-sleep cognitive activity compared to the " no instruction " group and that ( 2 ) " general distraction " would be associated with longer sleep onset latency and more frequent and distressing pre-sleep cognitive activity compared to the " no instruction " group . Support was found for the first but not the second prediction . The success of the " imagery distraction " task is attributed to it occupying sufficient " cognitive space " to keep the individual from re-engaging with thoughts , worries , and concerns during the pre-sleep period . In addition , " imagery distraction " involved a very specific alternative cognitive task hence the operating process was given a feature positive search , conditions where mental control is likely to be achieved Fifty-five insomniacs , 60 years or above , participated in a behavioral treatment program , comparing two interventions ( sleep hygiene+stimulus control vs sleep hygiene+relaxation tape ) . Half of the subjects were r and omized to a waiting-list condition prior to treatment . No significant changes were observed during the waiting-list period . During the treatment period however , the subjects improved on several sleep parameters , and treatment gains were maintained at a 6-month follow-up . The effects of treatment were greater for nocturnal measures ( e.g. sleep onset latency and total sleep time ) as compared to daytime measures ( e.g. life satisfaction , daytime alertness ) and not-targeted behavior ( medication use ) . There were no differences in treatment effects for the two interventions We compared day time functioning in college students with and without insomnia and explored changes in day time functioning after progressive relaxation ( PR ) treatment for insomnia . Students with insomnia ( SWI ; n = 57 ) were compared to a control group of students not complaining of insomnia ( SNI ; n = 61 ) on self-reported sleep variables and five question naires : Insomnia Impact Scale ( IIS ) , Dysfunctional Beliefs and Attitudes About Sleep Scale ( DBAS ) , Epworth Sleepiness Scale ( ESS ) , Fatigue Severity Scale ( FSS ) , and Penn State Worry Question naire ( PSWQ ) . SWI demonstrated significant impairment on all day time functioning and sleep measures compared to SNI . To investigate treatment effects on day time functioning , 28 SWI were r and omly assigned to PR . Treated SWI were compared to untreated SWI and SNI at posttreatment . Treated participants improved sleep in comparison to untreated SWI , but failed to show significant improvements in day time functioning . Insomnia treatments focused on improving sleep may not improve day time functioning , or day time gains may emerge more slowly than sleep gains . This study documents the wide range of day time functioning complaints in young adults with insomnia and suggests that the goal of insomnia treatment should be to not only improve sleep but also to improve the subjective experience of day time functioning We compared the efficacy of sleep restriction therapy combined with sleep hygiene , nap modification of sleep restriction therapy combined with sleep hygiene , and sleep hygiene alone as treatments for insomnia in 39 community-dwelling men and women 55 years and older . We used the wrist actigraph as an objective outcome measure for all subjects at baseline , end of treatment , and 3-month follow-up ; polysomnography ( PSG ) was conducted in a subgroup of subjects . Although subjects appeared to follow restriction instructions through follow-up , we found few between-group differences in treatment efficacy . Lack of treatment effect might be explained by the efficacy of HYG as a treatment in itself and the relatively low symptom level in these healthy older poor sleepers . At baseline , actigraphic results were found to correlate more highly than sleep log data with PSG in our sample . Actigraphic total sleep time , in particular , was highly correlated with PSG . ( J Geriatr Psychiatry Neurol 2000 ; 13:17 - 27 ) Insomnia is a common phenomenon in cancer patients ; nevertheless , there are only a few intervention results published covering this topic . We examined the effects of a multi-modal psychological sleep management programme combining relaxation techniques , sleep hygiene , cognitive techniques and advice in stimulus control technique on various sleep and quality -of-life variables . We compared two intervention groups up to 6 months after treatment , one with progressive muscle relaxation ( n=80 ) , the other with autogenic training ( n=71 ) . A control group ( n=78 ) received only a st and ard rehabilitation programme . It was a heterogeneous sample of adult patients ( mean age 58 years ) predominantly with breast , kidney or prostate cancer staying for 3 or 4 weeks in an oncological rehabilitation clinic . In comparison to the control group , the analysis of variance for repeated measures ( R-MANOVA ) showed significant improvements over time , indicating that intervention group participants benefited with moderate- or large-scale effects on sleep latency ( p<0.001 ) , sleep duration ( p<0.001 ) , sleep efficiency ( p<0.001 ) , sleep quality ( p<0.001 ) , sleep medication ( p<0.05 ) and daytime dysfunction ( p<0.05 ) . In quality -of-life subscales , there was mainly improvement over time . This may indicate a benefit of the rehabilitation treatment in general . No evidence was found for any differences between the two intervention groups . The results suggest that the use of a multi-modal psychological sleep intervention could enhance various sleep parameters and well being of patients . The efficacy on quality of life is still under review The present study tested cognitive-behavioral therapy ( CBT ) for insomnia in older adults with osteoarthritis , coronary artery disease , or pulmonary disease . Ninety-two participants ( mean age = 69 years ) were r and omly assigned to classroom CBT or stress management and wellness ( SMW ) training , which served as a placebo condition . Compared with SMW , CBT participants had larger improvements on 8 out of 10 self-report measures of sleep . The type of chronic disease had no impact on these outcomes . The hypothesis that CBT would improve daytime functioning more than SMW was only supported by a global rating measure . These results add to findings that challenge the dichotomy between primary and secondary insomnia and suggest that psychological factors are likely involved in insomnias that are presumed to be secondary to medical conditions A sample of 21 medicated and 20 nonmedicated insomniacs participated in a sleep medication withdrawal program that provided education about sleep medication and a , gradual medication withdrawal schedule . Ten medicated participants received stimulus control treatment and the withdrawal program , and 11 medicated participants served as a control grouip that received only the withdrawal program . Half of the nonmedicated participants received stimulus control , and the remaining nommedicated participants served as a wait-list control condition . Medicated participants significantly reduced sleep medication use without significant deterioration on sleep , anxiety , or depression measures from baseline to 8-week follow-up . Stimulus control participants , unlike control group participants , showed significant improvement at follow-up for total sleep time , sleep efficiency , and sleep quality . Stimulus control participants also reported less daytime sleepiness than control participants after treatment . Nonmedicated participants exhibited a more positive response to stimulus control than medicated participants Abstract The long-term effectiveness of a short-term cognitive-behavioral therapy was evaluated . The structured group treatment consisted of six weekly sessions and included progressive muscle relaxation , cognitive relaxation , modified stimulus control with bedtime restriction , thought stopping and cognitive restructuring . Twenty patients with chronic primary insomnia took part in the study . All patients were referred by physicians for diagnosis and therapy of insomnia . During a waiting period of six weeks prior to treatment , patients did not experience any change of their sleep parameters . After therapy , patients improved their total sleep time and sleep efficiency and reduced their sleep latency and negative sleep-related cognitions . Furthermore , depression scores decreased . Most of the treatment effects were significant at the end of the treatment and remained stable over the long-term follow-up , which was evaluated after a mean of almost three years ( 35±6.7 months ) . The subjective estimated total sleep time improved from 298±109 min prior to therapy to 351±54 min at the end of treatment , to 376±75 min at the 3-month follow-up , to 379±58 min at the 12-month follow-up and to 381±92 min . at the long-term follow-up Older adults with insomnia were recruited from the community and r and omized to treatments : relaxation , sleep compression , and placebo desensitization . Question naire data collected at baseline , posttreatment , and 1-year follow-up and polysomnography data collected at baseline and follow-up yielded the following conclusions : All treatments improved self-reported sleep , but objective sleep was unchanged . Clinical significance analyses yielded the strongest findings supporting the active treatments and suggested that sleep compression was most effective . Results partially supported the conclusion that individuals with high daytime impairment ( i.e. , fatigue ) respond best to treatments that extend sleep , as in relaxation , and individuals with low daytime impairment respond best to treatments that consoli date sleep , as in sleep compression . Strong method ological features including a placebo condition and a treatment implementation scheme elevate the confidence due these findings CONTEXT Use of nonpharmacological behavioral therapy has been suggested for treatment of chronic primary insomnia , but well-blinded , placebo-controlled trials demonstrating effective behavioral therapy for sleep-maintenance insomnia are lacking . OBJECTIVE To test the efficacy of a hybrid cognitive behavioral therapy ( CBT ) compared with both a first-generation behavioral treatment and a placebo therapy for treating primary sleep-maintenance insomnia . DESIGN AND SETTING R and omized , double-blind , placebo-controlled clinical trial conducted at a single academic medical center , with recruitment from January 1995 to July 1997 . PATIENTS Seventy-five adults ( n = 35 women ; mean age , 55.3 years ) with chronic primary sleep-maintenance insomnia ( mean duration of symptoms , 13.6 years ) . INTERVENTIONS Patients were r and omly assigned to receive CBT ( sleep education , stimulus control , and time-in-bed restrictions ; n = 25 ) , progressive muscle relaxation training ( RT ; n = 25 ) , or a quasi-desensitization ( placebo ) treatment ( n = 25 ) . Outpatient treatment lasted 6 weeks , with follow-up conducted at 6 months . MAIN OUTCOME MEASURES Objective ( polysomnography ) and subjective ( sleep log ) measures of total sleep time , middle and terminal wake time after sleep onset ( WASO ) , and sleep efficiency ; question naire measures of global insomnia symptoms , sleep-related self-efficacy , and mood . RESULTS Cognitive behavioral therapy produced larger improvements across the majority of outcome measures than did RT or placebo treatment . For example , sleep logs showed that CBT-treated patients achieved an average 54 % reduction in their WASO whereas RT-treated and placebo-treated patients , respectively , achieved only 16 % and 12 % reductions in this measure . Recipients of CBT also showed a greater normalization of sleep and subjective symptoms than did the other groups with an average sleep time of more than 6 hours , middle WASO of 26.6 minutes , and sleep efficiency of 85.1 % . In contrast , RT-treated patients continued to report a middle WASO of 43.3 minutes and sleep efficiency of 78.8 % . CONCLUSIONS Our results suggest that CBT represents a viable intervention for primary sleep-maintenance insomnia . This treatment leads to clinical ly significant sleep improvements within 6 weeks and these improvements appear to endure through 6 months of follow-up Discontinuous , nonnightly hypnotic therapy in the treatment of chronic insomnia is likely to offer benefits such as maintained efficacy while preventing unnecessary long-term nightly use associated with the risk of tolerance and dependence . Based on the favorable results seen in four zolpidem studies using increasing degrees of flexibility in drug intake schedule , we developed the concept further and investigated “ as needed ” zolpidem pharmacotherapy amended by the optional use of stimulus control in conditions close to the “ real life ” practice . In a prospect i ve , observational open study in 550 primary care setting s throughout Germany , 2690 patients with chronic insomnia ( mean age 59 years , 66 % female , 50 % with pharmacotherapy pretreatment ) were treated with zolpidem according to an “ as-needed ” ( pro re nata ) administration treatment schedule ( up to five tablets per week , intake nights chosen by the patient ) , amended by the optional use of behavioral therapy ( stimulus control ) during drug-free nights . After the three weeks ' treatment period , in two thirds of patients ( 63 % ) the weekly number of tablets used was reduced in contrast to baseline . The average zolpidem tablet number taken decreased by 28 % ( from 3.7 to 2.6 per week ; p < 0.00001 ) without any significant impact on the treatment efficacy assessed through the CGI . The subjective latency to sleep onset was reduced from a mean of 74 27 min ( p < 0.00001 ) and total sleep time increased from 5.0 to 6.8 h ( p < 0.00001 ) . Efficacy of treatment was rated as very good or good in 93 % by the investigators . Adverse events were observed only in 1.2 % of patients and were generally of mild nature . No serious adverse event occurred . These results underline the validity of the zolpidem “ as needed ” treatment concept . It is feasible in a safe and effective manner also in a primary care setting and can be amended by stimulus control . Further research is warranted on the contributions of both treatment components to effectiveness and on the efficacy and safety issues of long-term use AIMS To test the efficacy of a cognitive-behavioural approach to treating disturbed sleep in abstinent alcoholics . DESIGN Sixty recovering alcoholics with insomnia were assigned r and omly to individual therapy , self-help with telephone support or waiting-list control . SETTING Participants were volunteers recruited from out-patient treatment programs and through the media . MEASUREMENTS Outcomes were assessed at post-treatment , 3-month and 6-month follow-ups using sleep diaries , the Pittsburgh Sleep Quality Index , wrist actigraphs and time-line follow-back interviews . INTERVENTION Five sessions of out-patient cognitive-behavioural therapy for insomnia or a self-help manual with five telephone support calls . Treatment duration was 7 weeks . FINDINGS Treated participants were significantly more improved than control participants on diary measures of sleep quality , sleep efficiency , awakenings and time to fall asleep . No significant differences between the individual therapy and self-help treatment conditions on measures of insomnia severity were evident at post-treatment . Self-reported improvement in sleep was corroborated by clinician and spousal ratings of insomnia severity , but not by actigraph recordings of nocturnal activity . At 3- and 6-month follow-up assessment s treatment gains were reasonably maintained in both treatment groups , although individual therapy was associated with a higher rate of clinical ly significant improvement . At the 6-month follow-up , 60 % participants who were regular users of sedative medication at baseline discontinued the use of their medication . Treatment appeared to have little impact in preventing relapses to alcohol . CONCLUSIONS Recovering alcoholics with insomnia can achieve better sleep by applying cognitive-behavioural strategies OBJECTIVE The prevalence , burden , and management of insomnia among primary care patients were evaluated . METHOD Consecutive patients aged 18 to 65 years in primary care clinics of a staff-model health maintenance organization ( N = 1,962 ) were screened with the 12-item General Health Question naire . A stratified r and om sample ( N = 373 ) completed face-to-face diagnostic assessment s including the Composite International Diagnostic Interview , a brief self-rated disability question naire ( Brief Disability Question naire ) , and the interviewer-rated Social Disability Schedule . A telephone follow-up survey was completed 3 months later . Use of psychotropic drugs , use of mental health services , and direct health care costs were assessed by using the health plan 's automated data systems . RESULTS Approximately 10 % of the primary care patients reported major current insomnia ( e.g. , taking at least 2 hours to fall asleep nearly every night ) . Current insomnia was associated with significantly greater functional impairment ( according to both Brief Disability Question naire and Social Disability Schedule ) , more days of disability due to health problems , and greater general medical service utilization . While insomnia was associated with depressive disorder and chronic medical illness , adjustment for these factors only partially accounted for the association of insomnia with disability and with health care utilization . Of the patients with current insomnia , 28 % received any psychotropic drug ; 14 % received benzodiazepines and 19 % received antidepressants . CONCLUSIONS Insomnia among primary care patients is associated with greater functional impairment , lost productivity , and excess health care utilization PURPOSE Chronic insomnia is highly prevalent in cancer patients . Cognitive-behavioral therapy ( CBT ) is considered the treatment of choice for chronic primary insomnia . However , no r and omized controlled study has been conducted on its efficacy for insomnia secondary to cancer . Using a r and omized controlled design , this study conducted among breast cancer survivors evaluated the effect of CBT on sleep , assessed both subjectively and objective ly , and on hypnotic medication use , psychological distress , and quality of life . PATIENTS AND METHODS Fifty-seven women with insomnia caused or aggravated by breast cancer were r and omly assigned to CBT ( n = 27 ) or a waiting-list control condition ( n = 30 ) . The treatment consisted of eight weekly sessions administered in a group and combined the use of stimulus control , sleep restriction , cognitive therapy , sleep hygiene , and fatigue management . Follow-up evaluations were carried out 3 , 6 , and 12 months after the treatment . RESULTS Participants who received the insomnia treatment had significantly better subjective sleep indices ( daily sleep diary , Insomnia Severity Index ) , a lower frequency of medicated nights , lower levels of depression and anxiety , and greater global quality of life at post-treatment compared with participants of the control group after their waiting period . Results were more equivocal on polysomnographic indices . Therapeutic effects were well maintained up to 12 months after the intervention and generally were clinical ly significant . CONCLUSION This study supports the efficacy of CBT for insomnia secondary to breast cancer This study describes , and examines the initial efficacy of , a sleep therapy programme developed for cancer patients with insomnia . The six-session group programme included stimulus control therapy , relaxation training , and other strategies aim ed at consolidating sleep and reducing cognitive-emotional arousal . The 12 final participants were patients of a regional cancer centre ; mean age was 54.7 years ( S.D. 10.4 ) ; median time from cancer diagnosis was 33.6 months ; all had high performance status . Participants kept sleep diaries and rated their sleep quality , mood and functioning at baseline , week 4 and week 8 . Significant improvement over baseline was observed at weeks 4 and 8 in the number of awakenings , time awake after sleep onset , sleep efficiency , sleep quality ratings , and scores on European Organization for Research and Treatment of Cancer ( EORTC ) QLQ-C30 role functioning and insomnia . Total sleep time and fatigue were significantly improved at week 8 . The sleep therapy programme was associated with improved sleep , reduced fatigue and enhanced ability to perform activities in relatively well individuals attending a cancer centre . This is preliminary evidence of the efficacy of the programme . Further research is required to examine the programme 's effectiveness and suitability for a wider range of people with cancer . Options for providing cancer patients with access to nonpharmacologic treatments for insomnia are discussed Objective : To assess an uncontrolled , open-label trial of sleep-disordered breathing ( SDB ) treatment on two different sample s of chronic insomnia patients . Method : In Study 1 ( Retrospective ) , data from one diagnostic and one continuous positive airway pressure ( CPAP ) titration polysomnogram were compiled from 19 chronic insomnia patients with SDB . Objective polysomnogram indicators of sleep and arousal activity and self-reported sleep quality were measured . In Study 2 ( Prospect i ve ) , clinical outcomes were assessed after sequential cognitive-behavioral therapy ( CBT ) and SDB therapy ( CPAP , oral appliances , or bilateral turbinectomy ) were provided to 17 chronic insomnia patients with SDB . Repeat measures included the Insomnia Severity Index , Functional Outcomes of Sleep Question naire , Pittsburgh Sleep Quality Index , and self-reported insomnia indices and CPAP use . Results : In Study 1 , seven objective measures of sleep and arousal demonstrated or approached significant improvement during one night of CPAP titration . Sixteen of 19 patients reported improvement in sleep quality . In Study 2 , Insomnia Severity Index , Functional Outcomes of Sleep Question naire , and Pittsburgh Sleep Quality Index improved markedly with CBT followed by SDB treatment and achieved an average outcome equivalent to curative status . Improvements were large for each treatment phase ; however , of 17 patients , only 8 attained a non clinical level of insomnia after CBT compared with 15 patients after SDB therapy was added . Self-reported insomnia indices also improved markedly , and self-reported SDB therapy compliance was high . Conclusions : In one small sample of chronic insomnia patients with SDB , objective measures of insomnia , arousal , and sleep improved during one night of CPAP titration . In a second small sample , vali date d measures of insomnia , sleep quality , and sleep impairment demonstrated clinical cures or near-cures after combined CBT and SDB therapies . These pilot results suggest a potential value in research ing the pathophysiological relationships between SDB and chronic insomnia , which may be particularly relevant to patients with refractory insomnia OBJECTIVES This study was initially design ed to test the notion that generalized anxiety is a predominant factor in the maintenance of psychologically determined sleep-onset insomnia and that a trait anxiety reducing technique can provide significant therapeutic gains . METHODS Twenty participants ( age 19 - 63 ) with moderate to severe sleep-onset chronic insomnia were first asked to monitor their sleep-onset latency ( SOL ) for a 3-week baseline period at home using a SOL clock device . Then , 10 received anxiety management training ( AMT ) for 9 weeks , while the remaining 10 were trained in the use of progressive relaxation ( PR ) . All participants were measured before and after therapy using sleep laboratory recordings ( three nights each ) , the Spielberger Trait Anxiety Inventory and the Beck Depression Inventory . Daily home sleep-onset measures with the SOL clock device were also taken during therapy . RESULTS There was no change in SOL over the 3-week baseline period . However , both groups experienced a significant improvement in SOL from pretreatment ( end of baseline ) to posttreatment periods . In the laboratory , both groups experienced a reduction in Stage 1 sleep as well as an increase in slow wave sleep ( SWS ) and sleep satisfaction . On the personality measures , both groups experienced a significant reduction in trait anxiety and a decrease in depression . Overall , there was no indication that one of the therapies was significantly better than the other in effecting changes . CONCLUSION These results suggest that both PR and AMT are efficient therapies for sleep onset insomnia and overall sleep quality . Improvements in the application of the AMT technique are proposed to maximize its usefulness OBJECTIVES To identify predictors of treatment adherence , patient dropout , and treatment response among long-term hypnotic users recruited into a r and omized controlled trial of psychological treatment for insomnia . METHODS Of 108 treatment and 101 control patients initially recruited , 37 treatment group patients ( 34.3 % ) failed to complete all 6 sessions ( i.e. , were nonadherent ) , while across both groups 61 ( 29.2 % ) patients failed to return postal assessment s at 3-month follow-up ( i.e. , dropped out ) . Relationships between baseline characteristics and adherence ( adherent vs. nonadherent ) and attrition ( dropout vs. nondropout ) were examined in discriminant models . Relationships between baseline characteristics and treatment response ( sleep quality , sleep latency , sleep efficiency , and hypnotic drug use ) were examined in a series of multiple regression models . RESULTS Adherent patients showed a significantly greater severity of pretreatment sleep disturbance , as measured by the Pittsburgh Sleep Quality Index ( PSQI ) . Dropout at 3 months was associated with significantly lower perceived health status at baseline . In the regression models , lower Cure/Control subscale scores from the Illness Perception Question naire ( IPQ ) predicted greater posttreatment improvements in sleep efficiency and PSQI scores , while lower baseline anxiety scores predicted a posttreatment increase in hypnotic-free nights/week . CONCLUSION In routine clinical practice setting s , higher anxiety and a less positive attitude towards symptom control were associated with poorer treatment response . Adherence and attrition show a different pattern of associations , with greater need ( as indexed by insomnia severity ) predicting higher levels of service uptake and poorer general health predicting a higher likelihood of dropout OBJECTIVES To evaluate the efficacy and applicability of a behavioural treatment for insomnia that can be administered by family physicians in various clinical setting s. DESIGN Efficacy of the treatment was evaluated by single-case experimental design s ( multiple baseline across subjects ) . Applicability was assessed through semistructured interviews with physicians . SETTING Two private offices , two offices in community health centres , and one office in a family medicine unit . PARTICIPANTS Six general practitioners and 24 chronic insomniac patients recruited through media advertisements and from physicians ' practice s. Of an initial 38 subjects screened , six were excluded for sleep-onset latency less than 30 minutes , five for psychological conditions , one for physical h and icaps , and two for other reasons . INTERVENTIONS Physicians used stimulus-control treatment during individual therapeutic sessions . Patients using hypnotics were encouraged to taper off their medications after treatment was initiated . MAIN OUTCOME MEASURES Time it took patients to get to sleep ( sleep-onset latency ) , amount of hypnotic use , and practitioners ' evaluation of the treatment . RESULTS Fifteen patients completed the treatment ; 80 % of them reduced their sleep-onset latency . Six of the seven patients using hypnotics at the beginning of the study reduced or stopped their medications . All therapeutic gains were maintained at 3 and 6 months . Physicians thought stimulus-control treatment could be used in medical practice , but specified that it was most useful for highly motivated patients . CONCLUSION Family physicians can use stimulus-control treatment effectively for patients with chronic insomnia . This nonpharmacologic approach could help motivated patients reduce their use of hypnotics OBJECTIVES This study was conducted to test the effectiveness of an abbreviated cognitive-behavioral insomnia therapy ( ACBT ) with primary DESIGN A single-blind , r and omized group design was used in which study patients were r and omized to either a brief , 2-session ACBT or a similarly brief intervention ( SHC ) that included only generic sleep hygiene recommendations . SETTING A university-affiliated Department of Veterans Affairs medical center . PARTICIPANTS Twenty ( 2 women ) veteran patients ( M(age ) = 51.0 yrs . , SD = 13.7 years ) who met criteria for chronic primary insomnia . MEASUREMENTS AND RESULTS Participants completed sleep logs for 2 weeks and question naires to measures insomnia symptoms , sleep-related self-efficacy , and dysfunctional beliefs about sleep before treatment , during a 2-week posttreatment assessment , and again at a 3-month posttreatment follow-up . Statistical analyses showed that ACBT produced significantly larger improvements across a majority of outcome measures than did SHC . Case-by-case analyses showed that only the ACBT produced consistent positive effects across study patients , and a sizeable proportion of these patients receiving this treatment achieved clinical ly significant improvements by their study endpoints . Approximately 52 % of those receiving the ACBT reported at least a 50 % reduction in their wake time after sleep onset , and 55.6 % of ACBT-treated patients who entered the study with pathologic scores on an Insomnia Symptom Question naire ( ISQ ) , achieved normal ISQ scores by their final outcome assessment . CONCLUSIONS ACBT is effective for reducing subjective sleep disturbance and insomnia symptoms in primary care patients The methodology of assessing adherence to sleep restriction therapy for insomnia has received little attention in the empirical literature . The present study proposes and evaluates several approaches to assessing adherence to sleep restriction . We investigated multiple methods of measuring adherence and tested their utility by determining the strength of their association with treatment outcome in a sample of 22 older adults with insomnia ( 16 women , six men ) . As a group , the measures indicated reasonably good adherence to treatment recommendations . Time spent in bed was significantly reduced at post-treatment , and the night to night consistency of time spent in bed and arising time was significantly greater at post-treatment . However , time spent in bed per night at post-treatment still exceeded therapist recommendations by a mean of 27.89 min ( SD=31.72 ) . Greater consistency of time spent in bed per night and a more consistent arising time predicted a better treatment outcome . Measures of degree of bedtime reduction did not predict treatment outcome Patients with insomnia commonly complain that they are unable to get to sleep because of unwanted thoughts and worries . One account given of this excess cognitive activity is that it results from the incomplete processing of daytime stressors and hassles . Previous research has demonstrated the benefits of writing about emotional experiences as a method to facilitate emotional processing . This pilot study tested the hypothesis that writing about worries and concerns , with an emphasis on the expression and processing of emotion , will reduce sleep onset latency among an analogue sample of poor sleepers . Forty-two poor sleepers were r and omly allocated to 1 of 3 groups for 3 nights ; the instructions for the " problems " writing group emphasized the expression and processing of worries and concerns , the instructions for the " hobbies " writing group emphasized distraction from worries and concerns by writing about hobbies and interests , the " no writing " group were not given a writing task . The " problems " writing group reported shorter sleep onset latency compared to the " no writing " group . The results of this pilot study highlight the potential of research exploring the utility of a Pennebaker-style writing intervention for improving sleep BACKGROUND The literature on sleep disturbance in adults with intellectual disability ( ID ) is sparse . Although prevalence rates for sleep disorders appear similar to those of non-disabled population s , previous treatment studies have largely been comprised of uncontrolled cases . Therefore , the present study adopted a single-case experimental methodology to evaluate behavioural sleep intervention . METHODS A screening question naire was posted to 384 adults with ID and the sleep pattern of respondents with possible sleep disorders was further assessed using a structured diagnostic schedule . From the sleep-disordered subgroup , 12 participants were selected for a 4-week behavioural sleep intervention that was evaluated using r and omly allocated , multiple-baseline , across-subjects design s and within-subject interrupted time series analyses ( ITSAs ) . RESULTS A total of 155 adults with ID ( 83 females and 72 males ; mean age = 32 years , SD = 16.5 years ) , or their carers , completed the question naire ( return rate = 40 % ) . The application of sleep diagnostic criteria revealed that 17 % had clinical ly significant difficulty getting to sleep and 11 % had difficulty remaining asleep . Nine out of the 12 participants recruited for the intervention completed all the experimental phases , thus providing three sets of three multiple-baseline design s. Visual inspection of within- and between-subject effects suggested beneficial treatment-specific effects across a range of target variables . The ITSA confirmed significant effects ( P < 0.05 ) or trends ( P < 0.10 ) for six out of the nine participants . CONCLUSIONS Behavioural sleep management may improve sleep pattern or sleep-related functioning in the majority of adults with ID who have significant sleep problems . The single-case methodology is helpful in addressing the heterogeneity of individual presentation , although clinical trial methodology is required to confirm these findings on a larger scale Twenty-four older adults with persistent psychophysiological insomnia were r and omly assigned to an immediate or a delayed cognitive-behavioral intervention in a waiting-list control group design . Cognitive-behavior therapy consisted of an 8-week group intervention aim ed at changing maladaptive sleep habits and altering dysfunctional beliefs and attitudes about sleeplessness . Treatment was effective in reducing sleep latency , wake after sleep onset , and early morning awakening , and in increasing sleep efficiency . The magnitude of changes obtained on polysomnographic measures was smaller but in the same direction as that obtained on daily sleep diaries . Sleep improvements obtained by the immediate-treatment group were replicated with the delayed treatment condition . Therapeutic gains were well maintained at 3- and 12-month follow-ups . Clinical validation of outcome was obtained through collateral ratings from the patients and their significant others . The findings indicate that late-life insomnia can be effectively treated with nonpharmacological interventions In a longitudinal epidemiological study of young adults , we estimated the association between sleep disturbance and psychiatric disorders , cross-sectionally and prospect ively . A r and om sample of 1200 was drawn from all 21 - 30-year-old members of a large health maintenance organization ( HMO ) in Michigan ; 1007 were interviewed in 1989 and 979 were reinterviewed in 1992 . Lifetime prevalence of insomnia alone was 16.6 % , of hypersomnia alone , 8.2 % , and of insomnia plus hypersomnia , 8 % . The gender-adjusted relative risk for new onset of major depression during the follow-up period in persons with history of insomnia at baseline was 4.0 ( 95 % confidence interval [ CI ] 2.2 - 7.0 ) and in persons with baseline history of hypersomnia , 2.9 ( 95 % CI 1.5 - 5.6 ) . When history of other prior depressive symptoms ( e.g. , psychomotor retardation or agitation , suicidal ideation ) was controlled for , prior insomnia remained a significant predictor of subsequent major depression . Complaints of 2 weeks or more of insomnia nearly every night might be a useful marker of subsequent onset of major depression Sixty participants with insomnia secondary to chronic pain were assigned r and omly to either a cognitive-behavioral therapy ( CBT ) or a self-monitoring/waiting-list control condition . The therapy consisted of a multicomponent 7-week group intervention aim ed at promoting good sleep habits , teaching relaxation skills , and changing negative thoughts about sleep . Treated participants were significantly more improved than control participants on self-report measures of sleep onset latency , wake time after sleep onset , sleep efficiency , and sleep quality , and they showed less motor activity in ambulatory recordings of nocturnal movement . At a 3-month follow-up assessment , treated participants showed good maintenance of most therapeutic gains . These results provide the 1st evidence from a r and omized controlled trial that CBT is an effective treatment for insomnia that is secondary to chronically painful medical conditions Fifty-four adults with primary insomnia were r and omly assigned to a self-help treatment ( cognitive-behavioral bibliotherapy [ BT ] ) , BT with weekly phone consultations , or a waiting-list control ( WL ) group . Treated participants were mailed 6 treatment booklets at the rate of 1 booklet per week ; 1/2 of them also received minimal professional guidance through a 15-min weekly phone consultation . The WL group members continued to monitor their sleep during this period . Participants in both treatment conditions improved significantly on the main outcome variables ( total wake time and sleep efficiency ) at posttreatment , whereas WL participants remained unchanged . The addition of weekly phone calls slightly enhanced improvements at posttreatment . However , both treatment conditions were comparable at follow-up . These results suggest that BT , with or without minimal professional guidance , is an effective approach for treating primary insomnia BACKGROUND Long-term use of hypnotics is not recommended because of risks of dependency and adverse effects on health . The usual clinical management of benzodiazepine dependency is gradual tapering , but when used alone this method is not highly effective in achieving long-term discontinuation . We compared the efficacy of tapering plus cognitive-behavioural therapy for insomnia with tapering alone in reducing the use of hypnotics by older adults with insomnia . METHODS People with chronic insomnia who had been taking a benzodiazepine every night for more than 3 months were recruited through media advertisements or were referred by their family doctors . They were r and omly assigned to undergo either cognitive-behavioural therapy plus gradual tapering of the drug ( combined treatment ) or gradual tapering only . The cognitive-behavioural therapy was provided by a psychologist in 8 weekly small-group sessions . The tapering was supervised by a physician , who met weekly with each participant over an 8-week period . The main outcome measure was benzodiazepine discontinuation , confirmed by blood screening performed at each of 3 measurement points ( immediately after completion of treatment and at 3- and 12-month follow-ups ) . RESULTS Of the 344 potential participants , 65 ( mean age 67.4 years ) met the inclusion criteria and entered the study . The 2 study groups ( 35 subjects in the combined treatment group and 30 in the tapering group ) were similar in terms of demographic characteristics , duration of insomnia and hypnotic dosage . Immediately after completion of treatment , a greater proportion of patients in the combined treatment group had withdrawn from benzodiazepine use completely ( 77 % [ 26/34 ] v. 38 % [ 11/29 ] ; odds ratio [ OR ] 5.3 , 95 % confidence interval [ CI ] 1.8 - 16.2 ; OR after adjustment for initial benzodiazepine daily dose 7.9 , 95 % CI 2.4 - 30.9 ) . At the 12-month follow-up , the favourable outcome persisted ( 70 % [ 23/33 ] v. 24 % [ 7/29 ] ; OR 7.2 , 95 % CI 2.4 - 23.7 ; adjusted OR 7.6 , 95 % CI 2.5 - 26.6 ) ; similar results were obtained at 3 months . INTERPRETATION A combination of cognitive-behavioural therapy and benzodiazepine tapering was superior to tapering alone in the management of patients with insomnia and chronic benzodiazepine use . The beneficial effects were sustained for up to 1 year . Applying this multidisciplinary approach in the community could help reduce benzodiazepine use by older people BACKGROUND Daytime fatigue , if not frank sleepiness , is a common symptom among patients with insomnia , one that is exacerbated during acute treatment with cognitive behavior therapy ( CBT ) . The present study was undertaken to assess whether modafinil could be used to reduce daytime fatigue , sleepiness , or both in patients with primary insomnia and whether the pharmacologic augmentation of wakefulness might produce improved sleep by itself or in combination with CBT . METHODS 30 subjects with primary insomnia were enrolled in this study and were r and omly assigned to 1 of 3 treatment conditions : ( 1 ) placebo plus CBT , ( 2 ) 100 mg modafinil plus CBT , or ( 3 ) 100 mg modafinil plus a contact control ( monitor-only condition ) . Subjects were continuously monitored with sleep diaries from study intake until study end ( 10 weeks ) and were evaluated on a weekly basis for changes in sleepiness . RESULTS The mean age of the group was 41.3 years ( SD , 13.4 ) , and 70.4 % of subjects were women . All 3 groups exhibited mean sleep latency and wake after sleep-onset times that were more than 30 minutes in duration . The mean pretreatment sleep profiles did not significantly differ . Modafinil , when administered alone , did not significantly affect the patients ' sleep profiles . A trend , however , was evident for improved sleep latency . Modafinil , as an adjunct to CBT , tended to ( 1 ) reduce daytime sleepiness as measured by the Epworth Sleepiness Scale and ( 2 ) enhance compliance with CBT . With respect to the latter , subjects in the modafinil plus CBT group more reliably adhered to the prescribed phase delay in bedtime than did the placebo plus CBT group . DISCUSSION These data suggest that modafinil may be used to diminish the negative side effects of CBT ( increased daytime sleepiness ) and may increase subject compliance with therapy . Whether enhanced daytime function mediates the change in adherence and whether reduced sleepiness and enhanced compliance translate to less patient attrition in the clinical setting remain to be evaluated This paper describes a study in which progressive relaxation , EMG frontalis biofeedback , and a biofeedback placebo manipulation were compared in the treatment of severe insomnia with 40 chronically sleep-disturbed adult patients . Progressive relaxation and EMG biofeedback led to significant reductions in both reported sleep-onset latency and depressive symptomatology . However , when compared individually with the biofeedback placebo group , neither progressive relaxation nor EMG biofeedback emerged as significantly more effective on the sleep-onset latency measure . The clinical improvement in the biofeedback placebo group suggests that expectancies related to the ability to relax may contribute to the therapeutic effectiveness of relaxation strategies , even with chronic , severely disturbed insomniacs . Improvement in sleep-onset latency was not significantly related to reductions in frontalis EMG activity either within or between groups , a finding which raises questions concerning the clinical role and importance of physiological relaxation in the treatment of sleep-onset disturbance Chronic insomnia is a very common clinical condition which may respond well to non-pharmacological treatment . Indeed , the literature supports the efficacy of cognitive behaviour therapy ( CBT ) . However , there has been no substantial study of clinical effectiveness . Since insomniacs typically present in general medical practice this is a crucial gap in the outcome research . This study , therefore , specifically investigated the clinical effectiveness of CBT delivered by Health Visitors ( primary care nurses ) trained as therapists . One hundred and thirty-nine insomniacs ( mean age 51 yr ) were r and omised to CBT or Self-Monitoring Control ( SMC ) in a controlled trial . CBT comprised six group sessions ( n=4 to 6 patients ) . After the controlled phase , SMC patients entered deferred treatment ( CBT-DEF ) , allowing both treatment replication and long-term outcome to be investigated for a sizeable , treated sample . Repeated measures ANOVAs demonstrated superiority of CBT over SMC in substantially reducing sleep latency and wakefulness during the night . CBT-DEF replicated similar effects and maintained improvement was observed in both groups one year later . Furthermore , total sleep increased significantly during follow-up and 84 % of patients initially using hypnotics remained drug-free . Results suggest that CBT administered by Health Visitors offers a clinical ly effective treatment for insomnia This study investigated the effects of an Internet-based intervention for insomnia . Participants who met criteria for insomnia ( N = 109 ) were r and omly assigned to either a cognitive-behavioral self-help treatment or a waiting list control condition . The 5-week intervention mainly consisted of sleep restriction , stimulus control , and cognitive restructuring . Sleep diary data were collected for 2 weeks at baseline and at posttreatment . The dropout rate was 24 % ( n = 28 ) . Results showed statistically significant improvements in the treatment group on many outcome measures , including total sleep time , total wake time in bed , and sleep efficiency . However , improvements were also found in the control group . Overall , between-groups effect sizes were low , with the exception of the Beliefs and Attitudes About Sleep Scale ( Cohen 's d = .81 ) OBJECTIVE This study evaluated the effectiveness of a supervised benzodiazepine taper , singly and combined with cognitive behavior therapy , for benzodiazepine discontinuation in older adults with chronic insomnia . METHOD Seventy-six older adult out patients ( 38 women , 38 men ; mean age of 62.5 years ) with chronic insomnia and prolonged use ( mean duration of 19.3 years ) of benzodiazepine medication for sleep were r and omly assigned for a 10-week intervention consisting of a supervised benzodiazepine withdrawal program ( N=25 ) , cognitive behavior therapy for insomnia ( N=24 ) , or supervised withdrawal plus cognitive behavior therapy ( N=27 ) . Follow-up assessment s were conducted at 3 and 12 months . The main outcome measures were benzodiazepine use , sleep parameters , and anxiety and depressive symptoms . RESULTS All three interventions produced significant reductions in both the quantity ( 90 % reduction ) and frequency ( 80 % reduction ) of benzodiazepine use , and 63 % of the patients were drug-free within an average of 7 weeks . More patients who received medication taper plus cognitive behavior therapy ( 85 % ) were benzodiazepine-free after the initial intervention , compared to those who received medication taper alone ( 48 % ) and cognitive behavior therapy alone ( 54 % ) . The patients in the two groups that received cognitive behavior therapy perceived greater subjective sleep improvements than those who received medication taper alone . Polysomnographic data showed an increase in the amount of time spent in stages 3 and 4 sleep and REM sleep and a decrease in total sleep time across all three conditions from baseline to posttreatment . Initial benzodiazepine reductions were well maintained up to the 12-month follow-up , and sleep improvements became more noticeable over this period . No significant withdrawal symptoms or adverse events were associated with benzodiazepine tapering . CONCLUSIONS A structured , time-limited intervention is effective in assisting chronic users of benzodiazepine medication to discontinue or reduce their use of medication . The addition of cognitive behavior therapy alleviates insomnia , but sleep improvements may become noticeable only after several months of benzodiazepine abstinence This study compared the effectiveness of progressive relaxation training with and without a supplementary relaxation recording , which the subjects played at home , and an attention placebo manipulation in the modification of severe insomnia in adult volunteers . The results indicated that the relaxation training procedures were significantly more effective than placebo and no-treatment controls in modifying several parameters of sleeping behavior , in reducing consumption of sleep-inducing medication , and in influencing a self-report anxiety measure . The supplementary relaxation tape did not increase the effectiveness of relaxation training conducted in the clinic , and there was no difference in the efficacy of the placebo and no-treatment conditions . Physiological data gathered during the last treatment session indicated few significant correlations between reductions in arousal associated with relaxation training and treatment outcome . Recent years have witnessed increasing interest in the treatment of insomnia from a behavioral framework . Case studies and uncontrolled group investigations suggesting the effectiveness of relaxation training techniques and stimulus control procedures ( Bootzin , 1972 ; Geer & Katkin , 1966 ; Jacobson , 1964 ; Kahn , Baker , & Weiss , 1968 ) have given rise to controlled studies . Thus far this research has indicated that relaxation training procedures are effective in modifying several parameters of sleeping behavior in volunteer insomniacs . However , the mechanism(s ) by which this training operates have not been clearly identified . One possibility is that this technique works because of its placebo value . Relaxation training would seem to have high face validity for the treatment of insomnia , and the impressive proprioceptive muscle feedback often associated with the technique may add to its credibility , Although a number of studies have attempted to investigate this issue ( Borkovec & Fowles , 1973 ; Borkovec , Kaloupek , & Slama , 197S ; Borkovec , Steinmark , & Nan , 1973 ; Haynes , Woodward , Moron , & A sample of physician-referred chronic insomniacs was r and omly allocated to either progressive relaxation , stimulus control , paradoxical intention , placebo or no treatment conditions . Treatment process and outcome were investigated in terms of mean and st and ard deviation ( night to night variability ) measures of sleep pattern and sleep quality . Only active treatments were associated with significant improvement , but the nature of treatment gains varied . In particular , stimulus control improved sleep pattern , whereas relaxation affected perception of sleep quality . All improvements were maintained at 17 month follow-up . Results are discussed with reference to previous research and guidelines are given for clinical practice |
797 | 29,355,907 | When compared to traditional learning , e-learning may make little or no difference in patient outcomes or health professionals ' behaviours , skills or knowledge .
Even if e-learning could be more successful than traditional learning in particular medical education setting s , general cl aims of it as inherently more effective than traditional learning may be misleading | BACKGROUND The use of e-learning , defined as any educational intervention mediated electronically via the Internet , has steadily increased among health professionals worldwide .
Several studies have attempted to measure the effects of e-learning in medical practice , which has often been associated with large positive effects when compared to no intervention and with small positive effects when compared with traditional learning ( without access to e-learning ) .
However , results are not conclusive .
OBJECTIVES To assess the effects of e-learning programmes versus traditional learning in licensed health professionals for improving patient outcomes or health professionals ' behaviours , skills and knowledge . | Objective To compare the effectiveness of traditional and online teaching methods for educating anesthesiology residents in the principles and practice of difficult airway management . Design Prospect i ve , r and omized , controlled trial . Setting University hospital . Participants Two r and omly selected groups , each containing 28 physicians enrolled from among residents in Anesthesiology and Intensive Care Medicine in Italy . Interventions Residents in Group 1 took a traditional 5-h course on the principles and practice of airway management , which included lectures , slide projection , and dummy demonstrations . The same material was presented to Group 2 in an exclusively online format , which could be individually accessed for a period of 36 h. In the online course , student-instructor interaction was provided through threaded discussion forums during three 30-min real-time question - and -answer sessions . Measurements and results Differences in baseline and post-course scores on written tests and practical skills tests were measured . Knowledge gains in Group 2 were slightly , but not significantly , greater compared with Group 1 both in written ( P=0.228 ) and practical skills ( P=0.376 ) tests . Semi-quantitative ratings of learner satisfaction were significantly higher in the online group ( P=0.014 ) . Almost all online students ( 93 % ) were logged in for at least 45 of the 90 min of real-time question - and -answer sessions . The four instructors spent an average of 144±10 min preparing answers and interacting with online students . Conclusions Online teaching formats may be a valid alternative for teaching residents the principles and practice of difficult airway management . Interaction with instructors seems to be an important element , but it may require substantial time commitments by instructors AIMS AND OBJECTIVES To detect problems when classifying pressure ulcers and to examine whether an e-learning program is able to increase the classification skills of qualified nurses and nursing students . BACKGROUND Both the distinction between pressure ulcer grade s and the differentiation between moisture lesions is difficult . Misclassification and incorrect identification of the lesions results in inadequate preventive and therapeutic measures . Education and training are important for spreading evidence -based insights about this topic . DESIGN Repeated measure design , consisting of one pretest and three posttests . METHODS The experimental intervention consisted of a one-hour session during which the participants independently went over an e-learning program . The control intervention consisted of a one-hour lecture . Both interventions had the same learning contents . A convenience sample of 212 qualified nurses and 214 final-year nursing students was r and omly assigned to an experimental- and a control group . RESULTS In the pretest , the classification skills were low . After the intervention , these skills improved significantly in both groups . The nursing students achieved better results when using the e-learning program . Among the qualified nurses , there was no difference between the learning methods . Although the classification skills decreased in the posttests , they did not drop under the level of the pretest . CONCLUSION The actual classification system does not provide the necessary information about the severity of a pressure ulcer . The differential diagnosis between a moisture lesion was complicated . The classification skills of the qualified nurses and nursing students increased by both learning methods . Repetition remains , however , necessary . RELEVANCE TO CLINICAL PRACTICE Both instruction methods are adequate to acquire the knowledge about the differences between moisture lesions and pressure ulcers . E-learning allows study ing in one 's own time and place , and could therefore be very suitable for repetition of the training . How to organise this training could be a subject for further research Background Exercise is an effective intervention for the prevention of falls ; however , some forms of exercises have been shown to be more effective than others . There is a need to identify effective and efficient methods for training health professionals in exercise prescription for falls prevention . Objective The objective of our study was to compare two approaches for training clinicians in prescribing exercise to prevent falls . Methods This study was a head-to-head r and omized trial design . Participants were physiotherapists , occupational therapists , nurses , and exercise physiologists working in Victoria , Australia . Participants r and omly assigned to one group received face-to-face traditional education using a 1-day seminar format with additional video and written support material . The other participants received Web-based delivery of the equivalent educational material over a 4-week period with remote tutor facilitation . Outcomes were measured across levels 1 to 3 of Kirkpatrick ’s hierarchy of educational outcomes , including attendance , adherence , satisfaction , knowledge , and self-reported change in practice . Results Of the 166 participants initially recruited , there was gradual attrition from r and omization to participation in the trial ( n = 67 Web-based , n = 68 face-to-face ) , to completion of the educational content ( n = 44 Web-based , n = 50 face-to-face ) , to completion of the posteducation examinations ( n = 43 Web-based , n = 49 face-to-face ) . Participant satisfaction was not significantly different between the intervention groups : mean ( SD ) satisfaction with content and relevance of course material was 25.73 ( 5.14 ) in the Web-based and 26.11 ( 5.41 ) in the face-to-face group ; linear regression P = .75 ; and mean ( SD ) satisfaction with course facilitation and support was 11.61 ( 2.00 ) in the Web-based and 12.08 ( 1.54 ) in the face-to-face group ; linear regression P = .25 . Knowledge test results were comparable between the Web-based and face-to-face groups : median ( interquartile range [ IQR ] ) for the Web-based group was 90.00 ( 70.89–90.67 ) and for the face-to-face group was 80.56 ( 70.67–90.00 ) ; rank sum P = .07 . The median ( IQR ) scores for the exercise assignment were also comparable : Web-based , 78.6 ( 68.5–85.1 ) , and face-to-face , 78.6 ( 70.8–86.9 ) ; rank sum P = .61 . No significant difference was identified in Kirkpatrick ’s hierarchy domain change in practice : mean ( SD ) Web-based , 21.75 ( 4.40 ) , and face-to-face , 21.88 ( 3.24 ) ; linear regression P = .89 . Conclusion Web-based and face-to-face approaches to the delivery of education to clinicians on the subject of exercise prescription for falls prevention produced equivalent results in all of the outcome domains . Practical considerations should arguably drive choice of delivery method , which may favor Web-based provision for its ability to overcome access issues for health professionals in regional and remote setting s. Trial Registration Australian New Zeal and Clinical Trials Registry number : ACTRN12610000135011 ; http://www.anzctr.org.au/ACTRN12610000135011.aspx ( Archived by WebCite at http://www.webcitation.org/63MicDjPV OBJECTIVES : We report the results of a r and omized clinical trial of a 3-hour , web-based , tobacco cessation education program , the Web-Based Respiratory Education About Tobacco and Health ( WeBREATHe ) program , for practicing pediatric respiratory therapists ( RTs ) , registered nurses ( RNs ) , and nurse practitioners ( NPs ) . METHODS : Two hundred fifteen RTs ( n = 40 ) , RNs ( n = 163 ) , and NPs ( n = 12 ) employed at the Children ’s Hospital of Philadelphia and the Children ’s Hospital , University of Colorado at Denver , participated in this study . All study activities were completed online . After consenting , participants were r and omly assigned to either the training ( intervention ) or delayed training ( control ) condition . The training condition consisted of a 3-hour continuing education unit course plus ongoing online re sources . Participants were assessed at baseline , 1 week , and 3 months after enrollment . RESULTS : Participants in the training condition were more likely to increase their tobacco cessation intervention behaviors than their delayed training counterparts ( F[1 , 213 ] = 32.03 , P < .001 ) . Training participants showed significantly greater levels of advise ( F[1 , 213 ] = 7.22 , P < .001 ) ; assess ( F[1 , 213 ] = 19.56 , P < .001 ) ; and particularly assist/arrange ( F[1213 ] = 35.52 , P < .001 ) . In addition , training condition participants rated the program highly on measures of consumer satisfaction . CONCLUSIONS : The WeBREATHe program is the first evidence -based education program in tobacco cessation design ed specifically for pediatric RTs , RNs , and NPs . Engagement in WeBREATHe increased participants ’ tobacco cessation-related behaviors Background The introduction of Web-based education and open universities has seen an increase in access to professional development within the health professional education marketplace . Economic efficiencies of Web-based education and traditional face-to-face educational approaches have not been compared under r and omized controlled trial conditions . Objective To compare costs and effects of Web-based and face-to-face short courses in falls prevention education for health professionals . Methods We design ed two short courses to improve the clinical performance of health professionals in exercise prescription for falls prevention . One was developed for delivery in face-to-face mode and the other for online learning . Data were collected on learning outcomes including participation , satisfaction , knowledge acquisition , and change in practice , and combined with costs , savings , and benefits , to enable a break-even analysis from the perspective of the provider , cost-effectiveness analysis from the perspective of the health service , and cost-benefit analysis from the perspective of the participant . Results Face-to-face and Web-based delivery modalities produced comparable outcomes for participation , satisfaction , knowledge acquisition , and change in practice . Break-even analysis identified the Web-based educational approach to be robustly superior to face-to-face education , requiring a lower number of enrollments for the program to reach its break-even point . Cost-effectiveness analyses from the perspective of the health service and cost-benefit analysis from the perspective of the participant favored face-to-face education , although the outcomes were contingent on the sensitivity analysis applied ( eg , the fee structure used ) . Conclusions The Web-based educational approach was clearly more efficient from the perspective of the education provider . In the presence of relatively equivocal results for comparisons from other stakeholder perspectives , it is likely that providers would prefer to deliver education via a Web-based medium . Trial Registration Australian New Zeal and Clinical Trials Registry ( ACTRN ) : 12610000135011 ; http://www.anzctr.org.au/trial_view.aspx?id=335135 ( Archived by WebCite at http://www.webcitation.org/668POww4L The end of the twentieth century and the beginning of the twenty-first century are marked by technology revolution and strategic changes in organizations . Strategies such as the e-learning , has been used for training human re sources . This study aim ed to compare the knowledge acquired among groups of nurses who used e-learning and those who undergone a traditional classroom training . The true-experimental design was used followed by a quantitative analysis . This study was performed at the Hospital and Maternity São Luiz . The study population was composed by 60 nurses , r and omly assigned to two groups , named A and B. Group A received the traditional classroom training and group B received the computer-assisted training . In the data collection , participants filled in a question naire before and after the training to evaluate their knowledge and to characterize the population . Results showed there was an equal acquisition of knowledge in both groups ; confirming the efficacy of both methods Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged OBJECTIVE The authors conducted a feasibility assessment of online training plus an online learning collaborative to support implementation of an evidence -based psychosocial treatment in a community mental health system . METHODS Two mental health centers were r and omly allocated to in-person training with local supervision , and three were assigned to online training plus an online learning collaborative supported by expert clinicians . Participants ( N=36 ) were clinicians interested in interpersonal and social rhythm therapy ( IPSRT ) , an evidence -based psychotherapy for bipolar disorder . After training , 136 patients reported monthly on the extent to which clinicians used 19 IPSRT techniques . RESULTS Clinicians from both training groups increased use of IPSRT techniques . Patients of clinicians receiving Internet-supported e-learning and of those receiving in-person training reported comparable clinician use of IPSRT techniques . CONCLUSIONS Internet-supported e-learning by community clinicians was found to be feasible and led to uptake of an evidence -based psychotherapy comparable to that by clinicians who received face-to-face training Introduction Insufficient skills in drug dose calculations increase the risk for medication errors . Even experienced nurses may struggle with such calculations . Learning flexibility and cost considerations make e-learning interesting as an alternative to classroom teaching . This study compared the learning outcome and risk of error after a course in drug dose calculations for nurses with the two methods . Methods In a r and omised controlled open study , nurses from hospitals and primary healthcare were r and omised to either e-learning or classroom teaching . Before and after a 2-day course , the nurses underwent a multiple choice test in drug dose calculations : 14 tasks with four alternative answers ( score 0–14 ) , and a statement regarding the certainty of each answer ( score 0–3 ) . High risk of error was being certain that incorrect answer was correct . The results are given as the mean ( SD ) . Results 16 men and 167 women participated in the study , aged 42.0 ( 9.5 ) years with a working experience of 12.3 ( 9.5 ) years . The number of correct answers after e-learning was 11.6 ( 2.0 ) and after classroom teaching 11.9 ( 2.0 ) ( p=0.18 , NS ) ; improvement were 0.5 ( 1.6 ) and 0.9 ( 2.2 ) , respectively ( p=0.07 , NS ) . Classroom learning was significantly superior to e-learning among participants with a pretest score below 9 . In support of e-learning was evaluation of specific value for the working situation . There was no difference in risk of error between groups after the course ( p=0.77 ) . Conclusions The study showed no differences in learning outcome or risk of error between e-learning and classroom teaching in drug dose calculations . The overall learning outcome was small . Weak precourse knowledge was associated with better outcome after classroom teaching PURPOSE To evaluate the efficacy of the e-learning course " Genetics of Epilepsies " and to assess the experiences of the participants and e-moderators with this new approach . METHODS Prospect i ve , controlled study with waiting group ( control group , n = 18 ) and e-learning group ( n = 20 ) . The control group got the same reference literature list as the e-learning group . Both groups were assessed twice : The e-learning group before and after the course ; the control group was assessed at the same times . PRIMARY OUTCOME MEASURE increase in knowledge about genetics of epilepsies using question naires based on items formulated by experts ( internal consistency , Cronbach 's alpha = 0.86 ) . Main hypothesis : greater increase of knowledge in the e-learning group compared to control group . SECONDARY OUTCOME MEASURES assessment of the educational course and learning environment by participants and by tutors/e-moderators . RESULTS Significant time x group interaction and group effect ( ANOVA , each p < 0.01 ) with regard to knowledge . At baseline , the groups did not differ with respect to knowledge about genetics of epilepsy . In contrast to the control group , the increase of knowledge in the e-learning group was highly significant ( p < 0.001 ) . The majority of the participants of the e-learning course was content with their personal learning process ( 75 % agree , 15 % strongly agree ) . Most of them reported a gain in competence in the treatment and counseling of people with epilepsy ( 38.9 % agree , 50 % strongly agree ) . All participants would recommend this course to others and all but one participant are interested in other e-learning courses . CONCLUSION The study indicates e-learning courses are an appropriate tool to improve knowledge of physicians in genetics of epilepsy CONTEXT Despite evidence that a variety of continuing medical education ( CME ) techniques can foster physician behavioral change , there have been no r and omized trials comparing performance outcomes for physicians participating in Internet-based CME with physicians participating in a live CME intervention using approaches documented to be effective . OBJECTIVE To determine if Internet-based CME can produce changes comparable to those produced via live , small-group , interactive CME with respect to physician knowledge and behaviors that have an impact on patient care . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted from August 2001 to July 2002 . Participants were 97 primary care physicians drawn from 21 practice sites in Houston , Tex , including 7 community health centers and 14 private group practice s. A control group of 18 physicians from these same sites received no intervention . INTERVENTIONS Physicians were r and omly assigned to an Internet-based CME intervention that could be completed in multiple sessions over 2 weeks , or to a single live , small-group , interactive CME workshop . Both incorporated similar multifaceted instructional approaches demonstrated to be effective in live setting s. Content was based on the National Institutes of Health National Cholesterol Education Program -- Adult Treatment Panel III guidelines . MAIN OUTCOME MEASURES Knowledge was assessed immediately before the intervention , immediately after the intervention , and 12 weeks later . The percentage of high-risk patients who had appropriate lipid panel screening and pharmacotherapeutic treatment according to guidelines was documented with chart audits conducted over a 5-month period before intervention and a 5-month period after intervention . RESULTS Both interventions produced similar and significant immediate and 12-week knowledge gains , representing large increases in percentage of items correct ( pretest to posttest : 31.0 % [ 95 % confidence interval { CI } , 27.0%-35.0 % ] ; pretest to 12 weeks : 36.4 % [ 95 % CI , 32.2%-40.6 % ] ; P<.001 for all comparisons ) . Chart audits revealed high baseline screening rates in all study groups ( > or = 93 % ) with no significant postintervention change . However , the Internet-based intervention was associated with a significant increase in the percentage of high-risk patients treated with pharmacotherapeutics according to guidelines ( preintervention , 85.3 % ; postintervention , 90.3 % ; P = .04 ) . CONCLUSIONS Appropriately design ed , evidence -based online CME can produce objective ly measured changes in behavior as well as sustained gains in knowledge that are comparable or superior to those realized from effective live activities IMPORTANCE Dermoscopy permits the detection of early-stage melanomas but is difficult to learn . It is important to develop effective teaching methods . Spaced education is a methodology within the field of adaptive learning that uses online tools to reinforce long-term retention . OBJECTIVES To determine whether a spaced education dermoscopy module improved dermoscopy skills in the continuing medical education setting and to evaluate participant satisfaction . DESIGN , SETTING , AND PARTICIPANTS We design ed a prospect i ve controlled study with 2 sequential cohorts of participants enrolled between September 2010 and September 2013 , in the continuing medical education dermoscopy program of the Claude Bernard-Lyon 1 University in Lyon , France . Participants enrolled in this program were either certified dermatologists or senior dermatology residents . The control group ( n = 95 ) comprised all participants enrolled during the 2 first years of the study ( 49 participants in the class of 2010 , 46 in the class of 2011 ) . The intervention group ( n = 96 ) comprised all participants enrolled during the third and fourth years of the study ( 46 in the class of 2012 ; 50 in the class of 2013 ) . INTERVENTIONS All participants attended a 3-day lecture followed by small-group tutorials 4 months later . Each participant also attended a day of consultation with a dermoscopy specialist . In addition , participants in the intervention group were enrolled in an e-learning spaced education dermoscopy program . MAIN OUTCOMES AND MEASURES The main outcome measure was mean participant scores at the posttest evaluation , which was conducted 4 months after course enrollment . RESULTS The intervention group had better results at the posttest , with a mean ( SD ) score ( out of a possible 160.0 points ) of 148.1 ( 5.8 ) ( n = 82 participants ) vs 145.7 ( 7.7 ) ( n = 90 participants ) in the control group ( P = .02 ) . Ninety-two percent of the participants ( 80 of 87 ) were extremely or very satisfied with the e-learning module . Participant engagement was high , with an average of 85 % of participants ( 80 of 94 ) " on track " at any given time of the year . CONCLUSIONS AND RELEVANCE Our study shows that , in the context of continuing medical education , a spaced education Internet dermoscopy module combined with in-class training increases participant performances in dermoscopy . It is easy to use and adaptable to professional working schedules BACKGROUND R and omised studies examining the effect on patients of training professionals in adherence to suicide guidelines are scarce . AIMS To assess whether patients benefited from the training of professionals in adherence to suicide guidelines . METHOD In total 45 psychiatric departments were r and omised ( Dutch trial register : NTR3092 ) . In the intervention condition , all staff in the departments were trained with an e-learning supported train-the-trainer programme . After the intervention , patients were assessed at admission and at 3-month follow-up . Primary outcome was change in suicide ideation , assessed with the Beck Scale for Suicide Ideation . RESULTS For the total group of 566 patients with a positive score on the Beck Scale for Suicide Ideation at baseline , intention-to-treat analysis showed no effects of the intervention on patient outcomes at 3-month follow-up . Patients who were suicidal with a DSM-IV diagnosis of depression ( n = 154 ) showed a significant decrease in suicide ideation when treated in the intervention group . Patients in the intervention group more often reported that suicidality was discussed during treatment . CONCLUSIONS Overall , no effect of our intervention on patients was found . However , we did find a beneficial effect of the training of professionals on patients with depression The purpose of the study was to assess the effectiveness of supplementing traditional classroom teaching with Web-based learning design when teaching intramuscular injection nursing skills . Four clusters of nursing students at a junior college in eastern Taiwan were r and omly assigned to experimental and control groups . A total of 147 students ( 80 in the experimental group , 67 in the control group ) completed the study . All participants received the same classroom lectures and skill demonstration . The experimental group interacted using a Web-based course and were able to view the content on dem and . The students and instructor interacted via a chatroom , the bulletin board , and e-mail . Participants in the experimental group had significantly higher scores on both intramuscular injection knowledge and skill learning . A Web-based design can be an effective supplementing learning tool for teaching nursing knowledge and skills RATIONALE AND OBJECTIVES The aim of this study was to describe the impact of a tailored Web-based educational program design ed to reduce excessive screening mammography recall . MATERIAL S AND METHODS Radiologists enrolled in one of four mammography registries in the United States were invited to take part and were r and omly assigned to receive the intervention or to serve as controls . The controls were offered the intervention at the end of the study , and data collection included an assessment of their clinical practice as well . The intervention provided each radiologist with individual audit data for his or her sensitivity , specificity , recall rate , positive predictive value , and cancer detection rate compared to national benchmarks and peer comparisons for the same measures ; profiled breast cancer risk in each radiologist 's respective patient population s to illustrate how low breast cancer risk is in population -based setting s ; and evaluated the possible impact of medical mal practice concerns on recall rates . Participants ' recall rates from actual practice were evaluated for three time periods : the 9 months before the intervention was delivered to the intervention group ( baseline period ) , the 9 months between the intervention and control groups ( T1 ) , and the 9 months after completion of the intervention by the controls ( T2 ) . Logistic regression models examining the probability that a mammogram was recalled included indication of intervention versus control and time period ( baseline , T1 , and T2 ) . Interactions between the groups and time period were also included to determine if the association between time period and the probability of a positive result differed across groups . RESULTS Thirty-one radiologists who completed the continuing medical education intervention were included in the adjusted model comparing radiologists in the intervention group ( n = 22 ) to radiologists who completed the intervention in the control group ( n = 9 ) . At T1 , the intervention group had 12 % higher odds of positive mammographic results compared to the controls , after controlling for baseline ( odds ratio , 1.12 ; 95 % confidence interval , 1.00 - 1.27 ; P = .0569 ) . At T2 , a similar association was found , but it was not statistically significant ( odds ratio , 1.10 ; 95 % confidence interval , 0.96 to 1.25 ) . No associations were found among radiologists in the control group when comparing those who completed the continuing medical education intervention ( n = 9 ) to those who did not ( n = 10 ) . In addition , no associations were found between time period and recall rate among radiologists who set realistic goals . CONCLUSIONS This study result ed in a null effect , which may indicate that a single 1-hour intervention is not adequate to change excessive recall among radiologists who undertook the intervention being tested Background Web-based learning is becoming an increasingly important instructional tool in nursing education . Multimedia advancements offer the potential for creating authentic nursing activities for developing nursing competency in clinical practice . Objective This study aims to describe the design , development , and evaluation of an interactive multimedia Web-based simulation for developing nurses ’ competencies in acute nursing care . Methods Authentic nursing activities were developed in a Web-based simulation using a variety of instructional strategies including animation video , multimedia instructional material , virtual patients , and online quizzes . A r and omized controlled study was conducted on 67 registered nurses who were recruited from the general ward units of an acute care tertiary hospital . Following a baseline evaluation of all participants ’ clinical performance in a simulated clinical setting , the experimental group received 3 hours of Web-based simulation and completed a survey to evaluate their perceptions of the program . All participants were re-tested for their clinical performances using a vali date d tool . Results The clinical performance posttest scores of the experimental group improved significantly ( P<.001 ) from the pretest scores after the Web-based simulation . In addition , compared to the control group , the experimental group had significantly higher clinical performance posttest scores ( P<.001 ) after controlling the pretest scores . The participants from the experimental group were satisfied with their learning experience and gave positive ratings for the quality of the Web-based simulation . Themes emerging from the comments about the most valuable aspects of the Web-based simulation include relevance to practice , instructional strategies , and fostering problem solving . Conclusions Engaging in authentic nursing activities using interactive multimedia Web-based simulation can enhance nurses ’ competencies in acute care . Web-based simulations provide a promising educational tool in institutions where large groups of nurses need to be trained in acute nursing care and accessibility to repetitive training is essential for achieving long-term retention of clinical competency Background The effects of various educational strategies have been examined in continuing medical education . Web-based learning has emerged as an alternative to ordinary classroom lessons . Objective To investigate whether an interactive Web-based course including personal guidance via email or cellular phone texting may be used to improve practice behavior of general practitioners in the management of atopic dermatitis . Methods General practitioners from all over Norway were eligible for this r and omized controlled educational trial . During a period of 6 months , doctors in the intervention group were offered the opportunity to participate in a Web-based course on the management of atopic dermatitis . This was combined with guidance via email or multimedia messaging service ( MMS ) through mobile phones from a dermatologist . In the control group there was no education or guidance . Main outcome measures were the duration of topical steroid treatment prescribed to patients with atopic dermatitis ( primary outcome ) , number of treatment modalities , and number of referred patients . Results We enrolled 46 physicians : 24 doctors were allocated to the intervention group and 22 doctors to the control group . They reported a total of 190 patient treatments . There were no statistically significant differences in the duration of topical steroid treatment or number of treatment modalities between the groups . The lack of effect on the primary outcome may be due to attrition as 54 % ( 13/24 ) of the participants did not complete the course . 42 % ( 10/24 ) of physicians sent at least one educational request via email or MMS . While 11 % ( 8/73 ) of treatment reports in the intervention group were referred to a health care specialist ( eg , dermatologist or pediatrician ) , 30 % ( 21/71 ) of treatment reports in the control group did so . This difference in the number of referrals was significant ( P = .03 ) . Conclusions A Web-based educational intervention aim ed at general practitioners combined with personal support can reduce the number of atopic dermatitis patient referrals to specialists CONTEXT A well-suited e-learning program might be a feasible strategy to maintain competence following a resuscitation course . AIM This study had 2 aims : ( 1 ) to examine the effect of an e-learning program as a booster of competence acquired from an Advanced Life Support ( ALS ) course . ( 2 ) To identify factors related to the use of the e-learning program . MATERIAL S AND METHODS The study contained two parts pertaining to the two aims . The first part was a prospect i ve single blinded r and omised controlled study on junior doctors . The intervention was the monthly use of an e-learning program during one year and effect was measured as ALS-competence , a composite of a knowledge and skills test . The second part was a telephone interview of the intervention group . An interview guide was constructed based on existing knowledge of e-learning . In order to identify factors explaining the use of e-learning a univariate correlation was used to select significant variables to be included in a multiple regression analysis . RESULTS Of the 134 invited to participate , 103 accepted the invitation . There were 79/103 ( 77 % ) participants , 40/51 in the intervention group and 39/52 in the control group . There was no difference between the groups with regards to ALS competence . Only ' social interaction ' was an individually significant factor influencing the use of the e-learning program . CONCLUSIONS This study did not demonstrate an effect of an e-learning program as a booster of competence acquired from an ALS course . The primary factor influencing the use of e-learning was the lack of social interaction BACKGROUND Knowledge of quality measures in endoscopy among trainees is unknown . OBJECTIVE To assess knowledge of endoscopy-related quality indicators among U.S. trainees and determine whether it improves with a Web-based intervention . DESIGN R and omized , controlled study . SETTING Multicenter . PARTICIPANTS This study involved trainees identified from the American Society for Gastrointestinal Endoscopy membership data base . INTERVENTION Participants were invited to complete an 18- question online test . Respondents were r and omized to receive a Web-based tutorial ( intervention ) or not . The test was readministered 6 weeks after r and omization to determine the intervention 's impact . MAIN OUTCOME MEASUREMENTS Baseline knowledge of endoscopy-related quality indicators and impact of the tutorial . RESULTS A total of 347 of 1220 trainees ( 28 % ) completed the test ; the mean percentage of correct responses was 55 % . For screening colonoscopy , 44 % knew the adenoma detection rate benchmark , 42 % identified the cecal intubation rate goal , and 74 % knew the recommended minimum withdrawal time . A total of 208 of 347 trainees ( 59 % ) completed the second test ; baseline scores were similar for the tutorial ( n = 106 ) and no tutorial ( n = 102 ) groups ( 56.4 % vs 56.9 % , respectively ) . Scores improved after intervention for the tutorial group ( 65 % , P = .003 ) but remained unchanged in the no tutorial group . On multivariate analysis , each additional year in training ( odds ratio [ OR ] 2.3 ; 95 % confidence interval [ CI ] , 1.5 - 3.4 ) , training at an academic institution ( OR 2.6 ; 95 % CI , 1.1 - 6.3 ) , and receiving the tutorial ( OR 3.2 ; 95 % CI , 1.7 - 5.9 ) were associated with scores in the upper tertile . LIMITATIONS Low response rate . CONCLUSION Knowledge of endoscopy-related quality performance measures is low among trainees but can improve with a Web-based tutorial . Gastroenterology training programs may need to incorporate a formal didactic curriculum to supplement practice -based learning of quality st and ards in endoscopy Background The implementation of new medical knowledge into general practice is a complex process . Blended learning may offer an effective and efficient educational intervention to reduce the knowledge-to- practice gap . The aim of this study was to compare knowledge acquisition about dementia management between a blended learning approach using online modules in addition to quality circles ( QCs ) and QCs alone . Methods In this cluster-r and omised trial with QCs as clusters and general practitioners ( GPs ) as participants , 389 GPs from 26 QCs in the western part of Germany were invited to participate . Data on the GPs ' knowledge were obtained at three points in time by means of a question naire survey . Primary outcome was the knowledge gain before and after the interventions . A subgroup analysis of the users of the online modules was performed . Results 166 GPs were available for analysis and filled out a knowledge test at least two times . A significant increase of knowledge was found in both groups that indicated positive learning effects of both approaches . However , there was no significant difference between the groups . A subgroup analysis of the GPs who self-reported that they had actually used the online modules showed that they had a significant increase in their knowledge scores . Conclusion A blended learning approach was not superior to a QCs approach for improving knowledge about dementia management . However , a subgroup of GPs who were motivated to actually use the online modules had a gain in knowledge . Trial registration Current Controlled Trials IS RCT N36550981 BACKGROUND Pressure ulcers ( PUs ) are a problem in health care . Staff competency is paramount to PU prevention . Education is essential to increase skills in pressure ulcer classification and risk assessment . Currently , no pressure ulcer learning programs are available in Norwegian . OBJECTIVES Develop and test an e-learning program for assessment of pressure ulcer risk and pressure ulcer classification . METHODS DESIGN , PARTICIPANTS AND SETTING Forty-four nurses working in acute care hospital wards or nursing homes participated and were assigned r and omly into two groups : an e-learning program group ( intervention ) and a traditional classroom lecture group ( control ) . Data was collected immediately before and after training , and again after three months . The study was conducted at one nursing home and two hospitals between May and December 2012 . ANALYSIS Accuracy of risk assessment ( five patient cases ) and pressure ulcer classification ( 40 photos [ normal skin , pressure ulcer categories I-IV ] split in two sets ) were measured by comparing nurse evaluations in each of the two groups to a pre-established st and ard based on ratings by experts in pressure ulcer classification and risk assessment . Inter-rater reliability was measured by exact percent agreement and multi-rater Fleiss kappa . A Mann-Whitney U test was used for continuous sum score variables . RESULTS An e-learning program did not improve Braden subscale scoring . For pressure ulcer classification , however , the intervention group scored significantly higher than the control group on several of the categories in post-test immediately after training . However , after three months there were no significant differences in classification skills between the groups . CONCLUSION An e-learning program appears to have a greater effect on the accuracy of pressure ulcer classification than classroom teaching in the short term . For proficiency in Braden scoring , no significant effect of educational methods on learning results was detected BACKGROUND E-learning continues to proliferate as a method to deliver continuing medical education . The effectiveness of e-learning has been widely studied , showing that it is as effective as traditional forms of education . However , most reports focus on whether the e-learning is effective , rather than discussing innovations to allow clinical educators to ask ' how ' and ' why ' it is effective , and to facilitate local reproduction . CONTEXT Previous work has set out a number of barriers to the introduction of e-learning interventions . Cost , the time to produce interventions , and the training requirements for educators and trainees have all been identified as barriers . We set out to design an e-learning intervention on paediatric prescribing that could address these issues using a low-fidelity approach , and report our methods so as to allow interested readers to use a similar approach . INNOVATION Using low-cost , readily accessible tools and applying appropriate educational theory , the intervention was produced in a short period of time . As part of a r and omised controlled trial , long-term retention of prescribing skills was demonstrated , with significantly higher prescribing skill scores in the e-learning group at 4 and 12 weeks ( p < 0.0001 ) . Feedback was universally positive , with Likert responses suggesting that it was useful , convenient and easy to use . IMPLICATION S A low-fidelity approach to design ing can successfully overcome many of the barriers to the introduction of e-learning . The design model described is simple and can be used by clinical teachers to support local development . Further research could investigate the experiences of these clinicians using this method of instructional design The Ottawa Ethics of Cluster Trials Consensus Group sets out 15 recommendations for the ethical design and conduct of cluster r and omized trials Patients with inflammatory rheumatisms , such as rheumatoid arthritis , are more prone to develop skin cancers than the general population , with an additional increased incidence when receiving TNF blockers . There is therefore a need that physicians treating patients affected with inflammatory rheumatisms with TNF blockers recognize malignant skin lesions , requiring an urgent referral to the dermatologist and a potential withdrawal or modification of the immunomodulatory treatment . We aim ed to demonstrate that an online training dedicated to skin tumors increase the abilities of rheumatologists to discriminate skin cancers from benign skin tumors . A nationwide r and omized web-based survey involving 141 French rheumatologists was conducted . The baseline evaluation included short cases with skin lesion pictures and multiple choice questions assessing basic knowledge on skin cancers . For each case , rheumatologists had to indicate the nature of skin lesion ( benign ; premalignant/malignant ) , their level of confidence in this diagnosis ( 10-points Likert scale ) , and the precise dermatological diagnosis among 5 propositions . Different scores were established . After r and omization , only one group had access to the online formation consisting in 4 e-learning modules on skin tumors , of 15 minutes each ( online training group ) . After reevaluation , the trained and the non-trained group ( control group ) were compared . The primary end-point was the number of adequate diagnoses of the nature of the skin lesions . The mean number of adequate diagnosis for the benign versus premalignant/malignant nature of the lesions was higher in the online training group ( 13.4 vs. 11.2 points ; p value < 0.0001 ) . While the other knowledge scores were also significantly higher , no statistical difference was observed on the level of self-confidence between the 2 groups . In conclusion , the online formation was effective to improve the rheumatologists ’ ability to diagnose skin cancer Pressure ulcers ( PrU ) are considered as one of the most challenging problems that Nursing professionals have to deal with in their daily practice . Nowadays , the education on PrUs is mainly based on traditional lecturing , seminars and face-to-face instruction , sometimes with the support of photographs of wounds being used as teaching material . This traditional educational methodology suffers from some important limitations , which could affect the efficacy of the learning process . This current study has been design ed to introduce information and communication technologies ( ICT ) in the education on PrU for undergraduate students , with the main objective of evaluating the advantages an disadvantages of using ICT , by comparing the learning results obtained from using an e-learning tool with those from a traditional teaching methodology . In order to meet this major objective , a web-based learning system named ePULab has been design ed and developed as an adaptive e-learning tool for the autonomous acquisition of knowledge on PrU evaluation . This innovative system has been vali date d by means of a r and omized controlled trial that compares its learning efficacy with that from a control group receiving a traditional face-to-face instruction . Students using ePULab gave significantly better ( p<0.01 ) learning acquisition scores ( from pre-test mean 8.27 ( SD 1.39 ) to post-test mean 15.83 ( SD 2.52 ) ) than those following traditional lecture-style classes ( from pre-test mean 8.23 ( SD 1.23 ) to post-test mean 11.6 ( SD 2.52 ) ) . In this article , the ePULab software is described in detail and the results from that experimental educational validation study are also presented and analyzed The objective of this study was to measure reports of workplace violence ( WPV ) after an online training program on WPV for health care workers . Recognition of the prevalence of WPV ( physical , emotional-verbal , and sexual ) suggests a great need for employers to provide training to all health care workers as a first-line effort to reduce or prevent WPV . A 3-hour online training program for WPV was offered to 43 workers attending an informational session . Volunteers included 22 participants design ated for training and 21 volunteers design ated to serve as control subjects . Pretraining WPV work area assessment s were completed by all participants and compared between training participants and control subjects . At 6 months , comparisons were made between 3 groups : Group A , those who completed the training ; Group B , control subjects ; and Group C , those who did not complete the training within the design ated period . Group C was defined as a separate group because some participants within this group were workers from the same work areas as were Group A participants . Comparisons of pre assessment s and post assessment s of WPV for Group A and assessment s of WPV across the three groups were made . Participants reported 200 WPV events over a 6-month period before training . Pretraining reports of WPV were statistically different between training participants and control subjects for total and emotional-verbal WPV events . At 6 months after the training , a reduction in sample size and reports of all types of WPV was noted across the three groups ( i.e. , those who completed the training , those who did not complete it , and control subjects ) . Owing to the small number of reported physical and sexual WPV events , only total and emotional-verbal WPV events were examined . No difference was noted between the three groups for total events ; however , emotional-verbal abuse was statistically significant between the groups . In addition , a statistically significant difference was noted among participants before and after the completion of the online training . Despite the reported prevalence of WPV , a significant number of health care workers did not make training a priority . Participants who were design ated for training and who subsequently completed it reported the most number of events before and after training . Proportionately per number of participants after training , fewer total WPV events were reported ; however , because of the attrition rate and group sample size , significance was not reached . Reports of emotional-verbal abuse remained high after training , which could suggest a heightened awareness of this type of WPV with a personal redefinition of WPV or a heightened staff and administration sensitivity to reporting . Although differences existed among training participants and control subjects before training , significance could not be achieved among the three groups owing to validity threats , including subject mortality , diffusion between groups , selection bias , and small sample size . However , the finding that training can make a difference is important and encourages replication of this study with a larger sample size and a larger setting . Finding high rates of emotional-verbal abuse across work areas and support for training benefits enhance the need for training programs with an increased focus on emotional-verbal WPV Background In an effort to ensure that all physicians have access to valid and reliable evidence on drug effectiveness , the Italian Drug Agency sponsored a free-access e-learning system , based on Clinical Evidence , called ECCE . Doctors have access to an electronic version and related clinical vignettes . Correct answers to the interactive vignettes provide Continuing Medical Education credits . The aims of this trial are to establish whether the e-learning program ( ECCE ) increases physicians ' basic knowledge about common clinical scenarios , and whether ECCE is superior to the passive diffusion of information through the printed version of Clinical Evidence . Design All Italian doctors naïve to ECCE will be r and omised to three groups . Group one will have access to ECCE for Clinical Evidence chapters and vignettes lot A and will provide control data for Clinical Evidence chapters and vignettes lot B ; group two vice versa ; group three will receive the concise printed version of Clinical Evidence . There are in fact two design s : a before and after pragmatic trial utilising a two by two incomplete block design ( group one versus group two ) and a classical design ( group one and two versus group three ) . The primary outcome will be the retention of Clinical Evidence contents assessed from the scores for clinical vignettes selected from ECCE at least six months after the intervention . To avoid test-retest effects , we will r and omly select vignettes out of lot A and lot B , avoiding repetitions . In order to preserve the comparability of lots , we will select vignettes with similar , optimal psychometric characteristics . Trial registration IS RCT Objective Due to the gap in suicide-specific intervention training for mental health students and professionals , e-learning is one solution to improving provider skills in the Veterans Affairs ( VA ) health system . This study focused on the development and evaluation of an equivalent e-learning alternative to the Collaborative Assessment and Management of Suicidality ( CAMS ) in-person training approach at a Veteran Health Affairs medical center . Methods The study used a multicenter , r and omized , cluster , and three group design . the development of e-CAMS was an iterative process and included pilot testing . Eligible and consenting mental health providers , who completed a CAMS pre-survey , were r and omized . Provider satisfaction was assessed using the st and ard VA evaluation of training consisting of 20 items . Two post training focus groups , divided by learning conditions , were conducted to assess practice adoption using a protocol focused on experiences with training and delivery of CAMS . Results A total of 215 providers in five sites were r and omized to three conditions : 69 to e-learning , 70 to in-person , 76 to the control . The providers were primarily female , Caucasian , midlife providers . Based on frequency scores of satisfaction items , both learning groups rated the trainings positively . In focus groups representing divided by learning conditions , participants described positive reactions to CAMS training and similar individual and institutional barriers to full implementation of CAMS . Conclusions This is the first evaluation study of a suicide-specific e-learning training within the VA . The e-CAMS appears equivalent to the in-person CAMS in terms of provider satisfaction with training and practice adoption , consistent with other comparisons of training deliveries across specialty areas . Additional evaluation of provider confidence and adoption and patient outcomes is in progress . The e-CAMS has the potential to provide ongoing training for VA and military mental health providers and serve as a tutorial for psychiatrists in preparation for specialty boards Abstract Background : The management of psychiatric in patients exhibiting severely disturbed and aggressive behaviour is an important educational topic . Well structured , IT-based educational programmes ( eLearning ) often ensure quality and may make training more affordable and accessible . Aims : The aim of this study was to explore the impact of an eLearning course for personnel on the rates and duration of seclusion and mechanical restraint among psychiatric in patients . Methods : In a cluster-r and omized intervention trial , the nursing personnel on 10 wards were r and omly assigned to eLearning ( intervention ) or training-as-usual ( control ) groups . The eLearning course comprised six modules with specific topics ( legal and ethical issues , behaviour-related factors , therapeutic relationship and self-awareness , teamwork and integrating knowledge with practice ) and specific learning methods . The rates ( incidents per 1000 occupied bed days ) and duration s of the coercion incidents were examined before and after the course . Results : A total of 1283 coercion incidents ( 1143 seclusions [ 89 % ] and 140 incidents involving the use of mechanical restraints [ 11 % ] ) were recorded on the study wards during the data collection period . On the intervention wards , there were no statistically significant changes in the rates of seclusion and mechanical restraint . However , the duration of incidents involving mechanical restraints shortened from 36.0 to 4.0 h ( median ) ( P < 0.001 ) . No statistically significant changes occurred on the control wards . Conclusions : After our eLearning course , the duration of incidents involving the use of mechanical restraints decreased . However , more studies are needed to ensure that the content of the course focuses on the most important factors associated with the seclusion-related elements . The eLearning course deserves further development and further studies . The duration of coercion incidents merits attention in future research eLearning may facilitate continuing vocational education , but data on the long-term effects of an eLearning course are lacking . The aim of this study was to explore the long-term impact of an eLearning course entitled ePsychNurse . Net on psychiatric nurses ' professional competence in practicing seclusion and restraint and on their job satisfaction and general self-efficacy at 9-month follow-up . In a r and omized controlled study , 12 wards were r and omly assigned to the ePsychNurse . Net ( intervention ) or training as usual ( control ) . Baseline and 9-month follow-up data on nurses ' knowledge of coercion-related legislation , physical restraint and seclusion , their attitudes towards physical restraint and seclusion , job satisfaction and general self-efficacy were analysed for 137 completers ( those who participated in the 9-month follow-up assessment ) . No between-group differences were found on any variable , with the exception of a change in attitude to seclusion in favour of the control group . The findings of the long-term effects did not differ from the immediate outcomes ( 3-month follow-up ) and the improved level of knowledge acquired and further consolidation of that knowledge did not take place in the 6-month period after the 3-month ePsychNurse . Net course . The ePsychNurse . Net should be further developed and its future modifications will require additional studies , probably with some new outcome measures CONTEXT Selective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected , but direct evidence of such bias is currently limited to case reports . OBJECTIVE To study empirically the extent and nature of outcome reporting bias in a cohort of r and omized trials . DESIGN Cohort study using protocol s and published reports of r and omized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg , Denmark , in 1994 - 1995 . The number and characteristics of reported and unreported trial outcomes were recorded from protocol s , journal articles , and a survey of trialists . An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta- analysis . Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias . Protocol s and published articles were also compared to identify discrepancies in primary outcomes . MAIN OUTCOME MEASURES Completeness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes ; consistency between primary outcomes defined in the most recent protocol s and those defined in published articles . RESULTS One hundred two trials with 122 published journal articles and 3736 outcomes were identified . Overall , 50 % of efficacy and 65 % of harm outcomes per trial were incompletely reported . Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy ( pooled odds ratio , 2.4 ; 95 % confidence interval [ CI ] , 1.4 - 4.0 ) and harm ( pooled odds ratio , 4.7 ; 95 % CI , 1.8 - 12.0 ) data . In comparing published articles with protocol s , 62 % of trials had at least 1 primary outcome that was changed , introduced , or omitted . Eighty-six percent of survey responders ( 42/49 ) denied the existence of unreported outcomes despite clear evidence to the contrary . CONCLUSIONS The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocol s. Published articles , as well as review s that incorporate them , may therefore be unreliable and overestimate the benefits of an intervention . To ensure transparency , planned trials should be registered and protocol s should be made publicly available prior to trial completion Background Information about web-based education outcomes in comparison with a face-to-face format can help research ers and tutors prepare and deliver future web-based or face-to-face courses more efficiently . The aim of this study was to compare the effectiveness of web-based and face-to-face continuing education methods in improving nurses ' knowledge about AIDS . Methods A quasi-experimental method was used with a pre-test and post-test design . In this study 140 nurses with BSc degrees were chosen through a r and om sampling method and divided into a web-based and a face-to-face group by r and om allocation . For the former group the intervention consisted of a web-based course on AIDS ; the latter received a 3-hour lecture course on the same subject . At the beginning and end of the course in both groups , the nurses ' knowledge was measured by a question naire . Pre- and post-test scores were compared within and between the groups . Results The results show that there was no significant difference between the groups in either the pre-test ( t(138 ) = -1.7 , p = 0.096 ) nor the post-test ( t(138 ) = -1.4 , p = 0.163 ) scores in the knowledge test . However , there was a significant difference in the pre-test and post-test scores within each group ( web-based , t(69 ) = 26 , p < .001 ; face-to-face , t(69 ) = 24.3 , p < .001 ) . Conclusion The web-based method seems to be as effective as the face-to-face method in the continuing education of nurses . Therefore , the web-based method is recommended , as complementary to the face-to-face method , for design ing and delivering some topics of continuing education programs for nurses Background and Aims Examinations today are often computerized and the primary motivation and curriculum is often based on the examinations . This study aims to test if competition widgets in e-learning quiz modules improve post-test and follow-up test results and self-evaluation . The secondary aim is to evaluate improvements during the training period comparing test- results and number of tests taken . Methods Two groups were r and omly assigned to either a quiz-module with competition widgets or a module without . Pre- , post- and follow up test- results were recorded . Time used within the modules was measured and students reported time study ing . Students were able to choose questions from former examinations in the quiz-module . Results Students from the competing group were significantly better at both post- and follow-up-test and had a significantly better overall learning efficiency than those from the non-competing group . They were also significantly better at guessing their post-test results . Conclusion Quiz modules with competition widgets motivate students to become more active during the module and stimulate better total efficiency . They also generate improved self-awareness regarding post-test- results The use of the Internet makes it possible to bring together learners and teachers from rural areas and academic centers and to deliver well-accepted educational material s quickly and effectively . The objective of this study was to determine feasibility and the effectiveness of a problem-based small-group learning ( PBSGL ) intervention conducted via the Internet in a r and omized controlled trial . A group of 23 family physicians from rural Northern Ontario practice s and across Canada were r and omly assigned to a study group ( n = 11 ) and a control group ( n = 12 ) . The study group spent two months discussing the topic of depression in the elderly with the help of a facilitator and two geriatric psychiatrists . The control group was given similar educational re sources via the Internet but without the benefit of the small-group interaction . Outcome measures included qualitative feedback from the learners and teachers as well as a Multiple Choice Questions ( MCQ ) test before and after the study . The study provided important insight into the feasibility , keys to success , utility of Internet-assisted education from an education and evaluation perspective . Although the MCQ testing used revealed no significant differences between the study group and the control group , the usefulness of the measure is considered within the context of the educational approach . It is unclear whether this method of continuing medical education ( CME ) represents an effective way to conduct such activities To examine the effectiveness of a physiotherapy‐specific , web‐based e‐learning platform , “ RAP‐el , ” in best‐ practice management of rheumatoid arthritis ( RA ) using a single‐blind , r and omized controlled trial ( RCT ) and prospect i ve cohort study Objective Medication errors are common , with junior doctors accounting for the majority in acute healthcare . Paediatrics is uniquely challenging , but the evidence base to guide prescribing education is limited . The authors set out to develop a short , educationally sound , low cost e-learning re source for paediatric prescribing to improve junior doctors ' prescribing skills and to evaluate its effectiveness . Design A non-blinded r and omised controlled trial . Setting North Western Deanery Foundation School , UK . Participants 162 volunteer foundation ( junior ) doctors r and omised into control ( 86 ) and intervention ( 76 ) groups . Interventions On study entry , participants were assessed on prescribing skill , prescribing habits and confidence . The intervention group completed the e-learning course design ed for the study , which took 1–2 h. At 1 and 3 months after the intervention , both groups were assessed on similar prescribing assessment s , habits and confidence . Main outcome measures Total score ( expressed as a percentage ) on prescribing assessment s , confidence and satisfaction scores . Results There were no preintervention differences in prescribing assessment s ( 67 % vs 67 % , p=0.56 ) . Postintervention , the e-learning group scored significantly higher than the control group ( 63 % vs 79 % , p<0.0001 ) . At 3 months , the e-learning group still scored significantly higher ( 69 % vs 79 % , p<0.0001 ) , with improved confidence scores ( p<0.0001 ) . Conclusions This short e-learning re source significantly improved the paediatric prescribing skills of junior doctors . Outcomes were maintained at 3 months , suggesting the utility of low cost , low fidelity , educationally sound e-learning interventions . However , the direct impact on patient outcomes following this intervention has yet to be determined Background Within a clinical context e-learning is comparable to traditional approaches of continuing medical education ( CME ) . However , the occupational health context differs and until now the effect of postgraduate e-learning among occupational physicians ( OPs ) has not been evaluated . Aim To evaluate the effect of e-learning on knowledge on mental health issues as compared to lecture-based learning in a CME programme for OPs . Methods Within the context of a postgraduate meeting for 74 OPs , a r and omized controlled trial was conducted . Test assessment s of knowledge were made before and immediately after an educational session with either e-learning or lecture-based learning . Results In both groups , a significant gain in knowledge on mental health care was found ( P < 0.05 ) . However , there was no significant difference between the two educational approaches . Conclusion The effect of e-learning on OPs ' mental health care knowledge is comparable to a lecture-based approach . Therefore , e-learning can be beneficial for the CME of OPs PURPOSE Spaced education is a novel form of online education that harnesses the 2 psychology research findings of spacing and testing effects . Spaced education is delivered by daily emails containing clinical ly relevant multiple choice questions . To take advantage of the spacing effect the questions are repeated at fixed intervals for a fixed number of repetitions . An adaptive spaced education system was developed to customize spacing intervals and the number of repetitions based on learner knowledge level . To determine whether this system improves learning efficiency I performed a r and omized trial to compare the learning efficiency of adaptive vs nonadaptive spaced education systems among surgery students at 2 medical schools . MATERIAL S AND METHODS A total of 62 year 3 students were r and omized to identical course content in adaptive or nonadaptive spaced education formats . The course consisted of 40 vali date d , spaced education items on the 4 urology topics benign prostatic hyperplasia , erectile dysfunction , prostate cancer and prostate specific antigen screening . The nonadaptive cohort received daily emails containing 2 questions with a linear review of the material 20 days after initial presentation . The adaptive cohort received daily emails via an adaptive algorithm that limited the repetition of mastered content . Each cohort completed a vali date d end of course test . RESULTS The adaptive cohort answered significantly fewer spaced education items than the nonadaptive cohort ( p = 0.001 ) but achieved comparable end of course test scores ( p = 0.37 ) . The adaptive algorithm increased learning efficiency by 38 % . CONCLUSIONS Adaptive spaced education boosts learning efficiency Background Using information technology for medication management is an opportunity to help physicians to improve the quality of their documentation and communication and ultimately to improve patient care and patient safety . Physician education is necessary to take full advantage of information technology systems . In this trial , we seek to determine the effectiveness of an intensive educational intervention compared with the st and ard approach in improving information technology – mediated medication management and in reducing potential adverse drug events in the outpatient clinic . Methods / Design We are conducting a multicenter , cluster r and omized controlled trial . The participants are specialists and residents working in the outpatient clinic of internal medicine , cardiology , pulmonology , geriatrics , gastroenterology and rheumatology . The intensive educational intervention is composed of a small-group session and e-learning . The primary outcome is discrepancies between registered medication ( by physicians ) and actually used medication ( by patients ) . The key secondary outcomes are potential adverse events caused by missed drug – drug interactions . The primary and key secondary endpoints are being assessed shortly after the educational intervention is completed . Sample size will be calculated to ensure sufficient power . A sample size of 40 physicians per group and 20 patients per physician will ensure a power of > 90 % , which means we will need a total of 80 physicians and 1,600 patients . Discussion We performed an exploratory trial wherein we tested the recruitment process , e-learning , time schedule , and methods for data collection , data management and data analysis . Accordingly , we refined the processes and content : the recruitment strategy was intensified , extra measures were taken to facilitate smooth conductance of the e-learning and parts were made optional . First versions of the procedures for data collection were determined . Data entry and analysis was further st and ardized by using the G-st and ard data base in the telephone question naire . Trial registration IS RCT N registry : IS RCT N50890124 . Registered 10 June 2013 INTRODUCTION Emergency nurses deal with increasing complexity of patients . In 2003 there were over 14 million ED visits in Canada . The Canadian Triage and Acuity Scale ( CTAS ) is a 5-level system used by ED triage nurses to classify patients . There is a need for st and ardized training for all triage systems . In an effort to improve access to CTAS training , a 6-week Web-based CTAS workshop was developed . We determined the impact of Web learning on the accuracy of the triage skills of registered nurses ( RNs ) . METHODS An experimental method was used in which 132 RNs were r and omized to an intervention group ( n = 65 ) or control group ( n = 67 ) . All RNs received exactly the same content and learning activities . The experimental group differed from the control group in 3 ways : a m and atory tutorial , awarding of marks for online discussion , and completion of a workplace project . Data were collected using st and ard instruments , chart audit , and interviews . RESULTS The Web course provided a st and ardized and effective educational experience that enhanced emergency nurses ' triage accuracy . The m and atory online tutorial , online discussion , and workplace project increased the RNs ' preparation for online learning , and these educational methods were successful in transferring triage learning to practice . DISCUSSION Web learning can help professionals maintain competency and support professional practice . Further research is needed to provide evidence for best practice s in E-learning for RNs . The accuracy of the RN 's triage assessment impacts patient health , hospital accreditation , and funding Summary Background High-volume prescribing of antibiotics in primary care is a major driver of antibiotic resistance . Education of physicians and patients can lower prescribing levels , but it frequently relies on highly trained staff . We assessed whether internet-based training methods could alter prescribing practice s in multiple health-care systems . Methods After a baseline audit in October to December , 2010 , primary -care practice s in six European countries were cluster r and omised to usual care , training in the use of a C-reactive protein ( CRP ) test at point of care , in enhanced communication skills , or in both CRP and enhanced communication . Patients were recruited from February to May , 2011 . This trial is registered , number IS RCT N99871214 . Results The baseline audit , done in 259 practice s , provided data for 6771 patients with lower-respiratory-tract infections ( 3742 [ 55·3 % ] ) and upper-respiratory-tract infections ( 1416 [ 20·9 % ] ) , of whom 5355 ( 79·1 % ) were prescribed antibiotics . After r and omisation , 246 practice s were included and 4264 patients were recruited . The antibiotic prescribing rate was lower with CRP training than without ( 33 % vs 48 % , adjusted risk ratio 0·54 , 95 % CI 0·42–0·69 ) and with enhanced-communication training than without ( 36 % vs 45 % , 0·69 , 0·54–0·87 ) . The combined intervention was associated with the greatest reduction in prescribing rate ( CRP risk ratio 0·53 , 95 % CI 0·36–0·74 , p<0·0001 ; enhanced communication 0·68 , 0·50–0·89 , p=0·003 ; combined 0·38 , 0·25–0·55 , p<0·0001 ) . Interpretation Internet training achieved important reductions in antibiotic prescribing for respiratory-tract infections across language and cultural boundaries . Funding European Commission Framework Programme 6 , National Institute for Health Research , Research Foundation Fl and ers Medical professionals are increasingly expected to deliver genetic services in daily patient care . However , genetics education is considered to be suboptimal and in urgent need of revision and innovation . We design ed a Genetics e-learning Continuing Professional Development ( CPD ) module aim ed at improving general practitioners ’ ( GPs ’ ) knowledge about oncogenetics , and we conducted a r and omized controlled trial to evaluate the outcomes at the first two levels of the Kirkpatrick framework ( satisfaction , learning and behavior ) . Between September 2011 and March 2012 , a parallel-group , pre- and post-retention ( 6-month follow-up ) controlled group intervention trial was conducted , with repeated measurements using vali date d question naires . Eighty Dutch GP volunteers were r and omly assigned to the intervention or the control group . Satisfaction with the module was high , with the three item ’s scores in the range 4.1–4.3 ( 5-point scale ) and a global score of 7.9 ( 10-point scale ) . Knowledge gains post test and at retention test were 0.055 ( P<0.05 ) and 0.079 ( P<0.01 ) , respectively , with moderate effect sizes ( 0.27 and 0.31 , respectively ) . The participants appreciated applicability in daily practice of knowledge aspects ( item scores 3.3–3.8 , five-point scale ) , but scores on self-reported identification of disease , referral to a specialist and knowledge about the possibilities/ limitations of genetic testing were near neutral ( 2.7–2.8 , five-point scale ) . The Genetics e-learning CPD module proved to be a feasible , satisfactory and clinical ly applicable method to improve oncogenetics knowledge . The educational effects can inform further development of online genetics modules aim ed at improving physicians ’ genetics knowledge and could potentially be relevant internationally and across a wider range of potential audiences BACKGROUND Evidence -based guidelines are seen as an important instrument to transfer scientifically generated knowledge into daily clinical practice and to ensure high st and ards of clinical care . Despite wide promulgation , clinical guidelines so far have a limited impact on individual professional learning and on changing daily medical practice . OBJECTIVES Our aims were ( i ) to study a potential knowledge increase among German GPs after implementation of web- and evidence -based guidelines and ( ii ) to identify and analyse potential barriers to individual professional learning with computerized guidelines . METHODS A prospect i ve , r and omized controlled trial was conducted including 72 GPs ( 21 % female , 79 % male ) . The intervention group ( n = 38 ) had access to clinical guidelines via the Internet or CD-ROM , the control group had not ( n = 34 ) . Both groups received a st and ardized two-part question naire . An increase of knowledge was measured with 25 multiple choice questions related to four different medical topics . In addition , reasons for using or not using computerized guidelines were analysed after access to guidelines was open to all participating physicians . RESULTS There was no significant knowledge increase in the intervention group ( P = 0.69 ) . Twenty-two ( 58 % ) GPs of the intervention group had used the guidelines . Unspecified curiosity ( 76 % ) and a specific medical question ( 38 % ) were predominant motives for usage among physicians who had used the guidelines . Among ' non-users ' , 78 % stated ' lack of time ' as the main reason for not using guidelines . CONCLUSION An efficient knowledge transfer through computerized guidelines was not achieved . Usage , individual learning and potential implementation depend on adequate incentives and pragmatic aspects of clinical practice : easy and quick access Background Obstructive sleep apnea ( OSA ) and hypertension are well-known cardiovascular risk factors . Their control could reduce the burden of heart disease across population s. Several drugs are used to control hypertension , but the only consistently effective treatment of OSA is continuous positive airway pressure . The identification of a drug capable of improving OSA and hypertension simultaneously would provide a novel approach in the treatment of both diseases . Methods / Design This is a r and omized double-blind clinical trial , comparing the use of chlorthalidone with amiloride versus amlodipine as a first drug option in patients older than 40 years of age with stage I hypertension ( 140 to 159/90 to 99 mmHg ) and moderate OSA ( 15 to 30 apneas/hour of sleep ) . The primary outcomes are the variation of the number of apneas per hour and blood pressure measured by ambulatory blood pressure monitoring . The secondary outcomes are adverse events , somnolence scale ( Epworth ) , ventilatory parameters and C reactive protein levels . The follow-up will last 8 weeks . There will be 29 participants per group . The project has been approved by the ethics committee of our institution . Discussion The role of fluid retention in OSA has been known for several decades . The use of diuretics are well established in treating hypertension but have never been appropriately tested for sleep apnea . As well as testing the efficacy of these drugs , this study will help to underst and the mechanisms that link hypertension and sleep apnea and their treatment . Trial registration Clinical Trials.gov : Background Type 2 diabetes is one of the fastest growing chronic diseases internationally . The health complications associated with type 2 diabetes can be prevented , delayed , or improved via early diagnosis and effective management . This research aims to examine the impact of a primarily web-based educational intervention on the diabetes care provided by general practitioners ( GPs ) in rural areas , and subsequent patient outcomes . A population -level approach to outcome assessment is used , via whole-town de-identified pathology records . Methods / design The study uses a cluster r and omised controlled trial with rural communities as the unit of analysis . Towns from four Australian states were selected and matched on factors including rurality , population size , proportion of the population who were Indigenous Australians , and socio-economic status . Eleven pairs of towns from two states were suitable for the trial , and one town from each pair was r and omised to the experimental group . GPs in the towns allocated to the experimental group are offered an intervention package comprising education on best practice diabetes care via an on-line active learning module , a moderated discussion forum , access to targeted and specialist advice through an on-line request form , and town-based performance feedback on diabetes monitoring and outcomes . The package is offered via repeated direct mail . Discussion The benefits of the outcomes of the trial are described along with the challenges and limitations associated with the methodology .Trial registration Australian New Zeal and Clinical Trials Registry : BACKGROUND Traditional continuing medical education ( CME ) has not been successful in improving physicians ' practice . This project evaluated the use of e-mail to deliver evidence -based moderated case discussion s to family physicians . METHODS In a r and omized controlled trial , 58 southwestern Ontario physicians were recruited and r and omly assigned to receive two evidence -based cases ( type 2 diabetes , prevention ) or were put on a waiting list to receive the same . On-line discussion s took place about each case . Data were collected using two knowledge question naires , charts audits , and st and ardized patient visits for each of the two cases . RESULTS The two groups were similar except for rural/urban and solo versus group practice . The latter was related to outcomes , and analyses were controlled for this variable . The intervention group showed statistically significant improvements compared to the control group for knowledge and chart-audit scores for one of the two cases . CONCLUSIONS Using a r and omized control design , this e-mail CME method demonstrated mixed effectiveness Trial Design Best practice s for training mid-level practitioners ( MLPs ) to improve global health-services are not well-characterized . Two hypotheses were : 1 ) Integrated Management of Infectious Disease ( IMID ) training would improve clinical competence as tested with a single arm , pre-post design , and 2 ) on-site support ( OSS ) would yield additional improvements as tested with a cluster-r and omized trial . Methods Thirty-six Ug and an health facilities ( r and omized 1∶1 to parallel OSS and control arms ) enrolled two MLPs each . All MLPs participated in IMID ( 3-week core course , two 1-week boost sessions , distance learning ) . After the 3-week course , OSS-arm trainees participated in monthly OSS . Twelve written case scenarios tested clinical competencies in HIV/AIDS , tuberculosis , malaria , and other infectious diseases . Each participant completed different r and omly-assigned blocks of four scenarios before IMID ( t0 ) , after 3-week course ( t1 ) , and after second boost course ( t2 , 24 weeks after t1 ) . Scoring guides were harmonized with IMID content and Ug and an national policy . Score analyses used a linear mixed-effects model . The primary outcome measure was longitudinal change in scenario scores . Results Scores were available for 856 scenarios . Mean correct scores at t0 , t1 , and t2 were 39.3 % , 49.1 % , and 49.6 % , respectively . Mean score increases ( 95 % CI , p-value ) for t0–t1 ( pre-post period ) and t1–t2 ( parallel-arm period ) were 12.1 ( ( 9.6 , 14.6 ) , p<0.001 ) and −0.6 ( ( −3.1 , + 1.9 ) , p = 0.647 ) percent for OSS arm and 7.5 ( ( 5.0 , 10.0 ) , p<0.001 ) and 1.6 ( ( −1.0 , + 4.1 ) , p = 0.225 ) for control arm . The estimated mean difference in t1 to t2 score change , comparing arm A ( participated in OSS ) vs. arm B was −2.2 ( ( −5.8 , + 1.4 ) , p = 0.237 ) . From t0–t2 , mean scores increased for all 12 scenarios . Conclusions Clinical competence increased significantly after a 3-week core course ; improvement persisted for 24 weeks . No additional impact of OSS was observed . Data on clinical practice , facility-level performance and health outcomes will complete assessment of overall impact of IMID and OSS . Trial Registration Clinical Trials.gov Objective The development and evaluation of a computer‐assisted teaching programme of cardiotocog‐raphy and acid‐base balance With the increasing role of transoesophageal echocardiography in clinical fields other than cardiac surgery , we decided to assess the efficacy of multi‐modular echocardiography learning in echo‐naïve anaesthetic trainees . Twenty‐eight trainees undertook a pre‐test to ascertain basic echocardiography knowledge , following which the study subjects were r and omly assigned to two groups : learning via traditional methods such as review of guidelines and other literature ( non‐internet group ) ; and learning via an internet‐based echocardiography re source ( internet group ) . After this , subjects in both groups underwent simulation‐based echocardiography training . More tests were then conducted after a review of the respective educational re sources and simulation sessions . Mean ( SD ) scores of subjects in the non‐internet group were 28 (10)% , 44 (10)% and 63 (5)% in the pre‐test , post‐intervention test and post‐simulation test , respectively , whereas those in the internet group scored 29 (8)% , 59 (10)% , ( p = 0.001 ) and 72 (8)% , p = 0.005 , respectively . The use of internet‐ and simulation‐based learning methods led to a significant improvement in knowledge of transoesophageal echocardiography by anaesthetic trainees . The impact of simulation‐based training was greater in the group who did not use the internet‐based re source . We conclude that internet‐ and simulation‐based learning methods both improve transoesophageal echocardiography knowledge in echo‐naïve anaesthetic trainees A r and omized controlled study assessed a self-paced , online educational course addressing the complex nursing care of hospitalized patients on basal – bolus insulin . Interactive quizzes and scenarios were used to reinforce learning . Knowledge in the intervention group increased significantly and was retained 3-months postintervention . Nursing professional development educators will find this article useful regarding methods for annual competency evaluation and for increasing staff ’s knowledge as part of a system approach for safely caring for patients with diabetes BACKGROUND Previous interventions targeting primary care practitioners with the aim of increasing preventive care delivery have demonstrated limited effectiveness . The primary aim of this study was to assess the effectiveness of a computerized continuing medical education program to increase rates of three screening behaviors ( cholesterol , blood pressure , and cervical screening ) and to identify three risk behaviors ( smoking , alcohol consumption , benzodiazepine use ) in general practice . METHODS Nineteen general practitioners were r and omly allocated to intervention or control conditions . Those given the intervention received a computerized feedback system . The intervention was delivered using a touch-screen computer located in the surgery waiting area . The preventive behaviors of interest were patient smoking , alcohol use , benzodiazepine use , and blood pressure , cholesterol and cervical screening using the Papanicolou test . Differences in performance by group in each of the outcomes was measured at baseline and 3-month follow-up . Logistic regression analyses with generalized estimating equations were conducted as the main analyses . RESULT At 3-month follow-up , statistically significant differences were evident in the following outcome measures : accurate classification of benzodiazepine users ( z = 2.8540 , P < 0.05 ) ; accurate classification of non-benzodiazepine users ( z = 2.7339 , P < 0.05 ) ; accurate classification of hazardous or harmful alcohol drinkers ( z = 2.3079 , P < 0.02 ) ; blood pressure screening ( z = 3.4136 , P < 0.001 ) ; and cholesterol screening ( z = 6.6313 , P < 0.001 ) . CONCLUSION A computerized system of performance-specific feedback was effective at increasing some preventive care services in general practice BACKGROUND In light of widespread undertreatment for glucocorticoid-induced osteoporosis ( GIOP ) , we design ed a group r and omized controlled trial to increase bone mineral density ( BMD ) testing and osteoporosis medication prescribing among patients receiving long-term glucocorticoid therapy . METHODS Using administrative data bases of a large US health plan , we identified physicians who prescribed long-term glucocorticoid therapy to at least 3 patients . One hundred fifty-three participating physicians were r and omized to receive a 3-module Web-based GIOP intervention or control course . Intervention modules focused on GIOP management and incorporated case-based continuing medical education and personalized audit and feedback of GIOP management compared with that of the top 10 % of study physicians . In the year following the intervention , we compared rates of BMD testing and osteoporosis medication prescribing between intervention and control physicians . RESULTS Following the intervention , intent-to-treat analyses showed that 78 intervention physicians ( 472 patients ) vs 75 control physicians ( 477 patients ) had similar rates of BMD testing ( 19 % vs 21 % , P = .48 ; rate difference , -2 % ; 95 % confidence interval [ CI ] , -8 % to 4 % ) and osteoporosis medication prescribing ( 32 % vs 29 % , P = .34 ; rate difference , 3 % ; 95 % CI , -3 % to 9 % ) . Among 45 physicians completing all modules ( 343 patients ) , intervention physicians had numerically but not significantly higher rates of BMD testing ( 26 % vs 16 % , P = .04 ; rate difference , 10 % ; 95 % CI , 1%-20 % ) and bisphosphonate prescribing ( 24 % vs 17 % , P = .09 ; rate difference , 7 % ; 95 % CI , -1 % to 16 % ) or met a combined end point of BMD testing or osteoporosis medication prescribing ( 54 % vs 44 % , P = .07 ; rate difference , 10 % ; 95 % CI , -1 % to 21 % ) compared with control physicians . CONCLUSIONS In the main analysis , a Web-based intervention incorporating performance audit and feedback and case-based continuing medical education had no significant effect on the quality of osteoporosis care . However , dose-response trends showed that physicians with greater exposure to the intervention had higher rates of GIOP management . New cost-effective modalities are needed to improve the quality of osteoporosis care Objectives Child care centers have recently become targets for overweight prevention efforts directed at young children . Child Care Health Consultants ( CCHCs ) , who provide consultation to these centers , receive little training on the basic nutrition and physical activity principles important for the promotion of child healthy weight . Traditional approaches , such as in-person training , are limited in their ability to disseminate health information to a geographically diverse population of health professionals . The purpose of this study was to determine if web-based training is as effective as in-person training . Methods A r and omized controlled trial was conducted between August 2005 and June 2006 with 50 CCHCs . Web-based and in-person trained CCHCs were compared to each other and to controls . The main outcome of this study was performance on a test of nutrition knowledge related to childhood overweight measured by a 28-item multiple choice test administered pre- and post-training . Results Results from the ANCOVA model suggest that web trained CCHCs performed similarly to in-person trained CCHCs on the knowledge test ( P < .0001 ) . Additionally , both training groups improved significantly compared to controls ( P < .0001 for each group ) . Conclusions This study found no significant differences in post-training knowledge between in-person and web trained Child Care Health Consultants . Scores on the post-training knowledge test were within 0.5 points for the in-person and web trained groups . These results demonstrate that web-based instruction is as effective as in-person training on improving basic nutrition and physical activity knowledge for promoting healthy weight in preschool children Background and objective : Every member of healthcare personnel should be able to perform basic life support including defibrillation ( CPR‐D ) . The biggest cost of implementation is training and these costs need to be reduced . The purpose of this r and omized study was to evaluate the applicability of distance learning as a method to teach CPR‐D. Methods : Nurses ( n = 56 ) working in a geriatric hospital were r and omized into three groups . The first group was given the Internet‐based CPR‐D course and the second was given a traditional , small‐group CPR‐D course . A third group without specific training in CPR‐D served as a control group . An objective structured clinical examination ( OSCE ) was performed 2 weeks after the courses with a manikin patient having a cardiac arrest . Results : The median score of all participants was 31/49 ( range 21–38 ) . The reliability of the checklist was adequate ( Cronbach alpha 0.77 ) . Nurses receiving traditional CPR‐D performed better than those receiving the Internet‐based course ( median score 34 vs. 28 , P < 0.05 ) and the control group ( median score 34 vs. 26 , P < 0.0001 ) . Nurses receiving Internet‐based course performed similarly as the control group ( median score 28 vs. 26 , ns ) . Conclusions : Distance learning can not substitute for traditional small‐group learning Delirium is a significant problem for older hospitalized people and is associated with poor outcomes . It is poorly recognized and evidence suggests that a major reason is lack of education . Nurses , who are educated about delirium , can play a significant role in improving delirium recognition . This study evaluated the impact of a delirium specific educational website . A cluster r and omized controlled trial , with a pretest/post-test time series design , was conducted to measure delirium knowledge ( DK ) and delirium recognition ( DR ) over three time-points . Statistically significant differences were found between the intervention and non-intervention group . The intervention groups ' DK scores were higher and the change over time results were statistically significant [ T3 and T1 ( t=3.78 p=<0.001 ) and T2 and T1 baseline ( t=5.83 p=<0.001 ) ] . Statistically significant improvements were also seen for DR when comparing T2 and T1 results ( t=2.56 p=0.011 ) between both groups but not for changes in DR scores between T3 and T1 ( t=1.80 p=0.074 ) . Participants rated the website highly on the visual , functional and content elements . This study supports the concept that web-based delirium learning is an effective and satisfying method of information delivery for registered nurses . Future research is required to investigate clinical outcomes as a result of this web-based education Objective : To assess the efficacy of a “ spaced-education ” game as a method of continuing medical education ( CME ) among physicians across the globe . Background : The efficacy of educational games for the CME has yet to be established . We created a novel online educational game by incorporating game mechanics into “ spaced education ” ( SE ) , an evidence -based method of online CME . Methods : This 34-week r and omized trial enrolled practicing urologists across the globe . The SE game consisted of 40 vali date d multiple-choice questions and explanations on urology clinical guidelines . Enrollees were r and omized to 2 cohorts : cohort A physicians were sent 2 questions via an automated e-mail system every 2 days , and cohort B physicians were sent 4 questions every 4 days . Adaptive game mechanics re-sent the questions in 12 or 24 days if answered incorrectly and correctly , respectively . Questions expired if not answered on time ( appointment dynamic ) . Physicians retired questions by answering each correctly twice-in-a-row ( progression dynamic ) . Competition was fostered by posting relative performance among physicians . Main outcome measures were baseline scores ( percentage of questions answered correctly upon initial presentation ) and completion scores ( percentage of questions retired ) . Results : A total of 1470 physicians from 63 countries enrolled . Median baseline score was 48 % ( interquartile range [ IQR ] 17 ) and , in multivariate analyses , was found to vary significantly by region ( Cohen dmax = 0.31 , P = 0.001 ) and age ( dmax = 0.41 , P < 0.001 ) . Median completion score was 98 % ( IQR 25 ) and varied significantly by age ( dmax = 0.21 , P < 0.001 ) and American Board of Urology certification ( d = 0.10 , P = 0.033 ) but not by region ( multivariate analyses ) . Question clustering reduced physicians ' performance ( d = 0.43 , P < 0.001 ) . Seventy-six percent of enrollees ( 1111/1470 ) requested to participate in future SE games . Conclusions : An online SE game can substantially improve guidlines knowledge and is a well-accepted method of global CME delivery Internet-based lectures are a popular means of disseminating medical knowledge , but the impact of osteoporosis lectures on physician knowledge and patient care is unknown . We design ed an Internet-based lecture discussing the prevalence of , screening guidelines for , risk factors for , and physical signs of osteoporosis . Immediately before and after viewing the lecture , 6 physician participants completed question naires to gauge change in knowledge . From each participant 's clinic , we r and omly selected and review ed 10 charts of new female patients at least 60 yr old , half before and half after the lecture . Charts were blindly scored to determine physician attention to screening guidelines for , risk factors for , and signs of osteoporosis . Physician knowledge increased significantly after the lecture , with mean pretest and posttest scores of 63 % and 99 % , respectively ( p=0.03 ) . However , physician attention to patient risk factors for and signs of osteoporosis did not change after lecture " attendance . " Surprisingly , no patients who met age-specific screening guidelines ( age > or = 65 yr and no prior dual energy X-ray absorptiometry [ DXA ] ) were referred for DXA , either before or after study participation . We conclude that physician knowledge can increase after a single online osteoporosis lecture , but patient care is not altered . Further research is needed to discern optimal osteoporosis educational encounters that enhance patient care STUDY OBJECTIVE Training physicians in new skills through classroom-based teaching has inherent cost and time constraints . We seek to evaluate whether Web-based didactics result in similar knowledge improvement and retention of basic ultrasonographic principles and the Extended Focused Assessment with Sonography for Trauma ( EFAST ) compared with the traditional method . METHODS Physicians from 2 German emergency departments were r and omized into a classroom group with traditional lectures and a Web group who watched narrated lectures online . All participants completed a pre- and posttest and a second posttest 8 weeks later . Both groups underwent h and s-on training after the first posttest . A control group completed the 2 initial tests without didactic intervention . RESULTS Fifty-five subjects participated in the study . Both the classroom and Web group showed significant improvement in pre- and posttest 1 scores ( 75.9 % versus 93.9 % and 77.8 % versus 92.5 % ; P<.001 for both ) , with similar knowledge retention after 8 weeks ( 88.6 % and 88.9 % ; P=.87 ) . No statistically significant difference in mean test scores could be found between the 2 groups at each point : -1.9 % ( 95 % confidence interval [ CI ] -5.2 % to 1.4 % ) for the pretest , 1.4 % ( 95 % CI -0.6 % to 3.4 % ) for posttest 1 , and -0.3 % ( 95 % CI -3.9 % to 3.3 % ) for posttest 2 . The control group showed no learning effect without intervention ( 83.3 % versus 82.8 % , ; P=.88 ) . CONCLUSION Web-based learning provides the potential to teach physicians with greater flexibility than classroom instruction . Our data suggest that Web-based ultrasonography and EFAST didactics are comparable to traditional classroom lectures and result in similar knowledge retention BACKGROUND Primary care physicians ( PCPs ) have a major responsibility in the management of palliative patients . Online palliative care ( PC ) education has not been shown to have a clinical impact on patients that is equal or different to traditional training . OBJECTIVE This study tested the clinical effectiveness of online PC education of physicians through impact on symptom control , quality of life ( QOL ) , caregiver satisfaction , and knowledge-attitude of physicians at 18 months of the intervention . METHODS We conducted a r and omized clinical trial . Subjects were 169 physicians r and omly assigned to receive the online model or traditional training . Consecutive patients with advanced cancer requiring PC were included . Physicians and patients completed the Palliative Care Outcome Scale ( POS ) , and patients the Brief Pain Inventory ( BPI ) and the Rotterdam Symptom Checklist ( RSCL ) twice , 7 to 10 days apart . Caregivers completed the SERVQUAL . Physicians ' level of knowledge-attitude was measured at 18 months . RESULTS Sixty-seven physicians enrolled 117 patients . The intervention group had reduced scores for pain , symptoms , and family anxiety . The global RSCL scale showed a difference between groups . There was no significant difference in the question naires used . Caregiver satisfaction was comparable between groups . Physicians in the intervention group significantly increased their knowledge without any differences in attitude . Online training was completed by 86.6 % in the intervention group , whereas 13.4 % in the control group accessed traditional training . CONCLUSIONS Participation in an online PC education program by PCPs improved patient scores for some symptoms and family anxiety on the POS and also showed improved global QOL . Significant differences were found in physicians ' knowledge at short and long term BACKGROUND Cardiovascular risk reduction in ambulatory patients who survive myocardial infa rct ion ( MI ) is effective but underused . We sought to evaluate a provider-directed , Internet-delivered intervention to improve cardiovascular management for post-MI out patients . METHODS The Department of Veterans Affairs ( VA ) MI-Plus study was a cluster-r and omized trial involving 168 community-based primary care clinics and 847 providers in 26 states , the Virgin Isl and s , and Puerto Rico , from January 1 , 2002 , through December 31 , 2008 , with the clinic as the r and omization unit . We collected administrative data for 15,847 post-MI patients and medical record data for 10,452 of these . A multicomponent , Internet-delivered intervention included quarterly educational modules , practice guidelines , monthly literature summaries , and automated e-mail reminders delivered to providers for 27 months . Main outcome measures included percentage of patients who achieved each of 7 clinical indicators , a composite score of the 7 clinical indicators , and mean low-density lipoprotein cholesterol and hemoglobin A(1c ) levels . RESULTS Clinics had a median of 3 providers ( interquartile range , 2 - 6 ) , with a median of 50.0 % of providers ( 33.3%-66.7 % ) participating in the study . Patients in intervention clinics had greater improvements ( from 70.0 % to 85.5 % ) in the percentages prescribed β-blockers than patients in control clinics ( 71.9 % to 84.0 % ; adjusted improvement gain for intervention vs control , 2.6 % ; 95 % CI , 0.1%-4.1 % ) . We found nonsignificant differences in improvements favoring patients in intervention clinics for 5 of 6 remaining clinical indicators and levels of low-density lipoprotein cholesterol and hemoglobin A(1c ) . CONCLUSION A longitudinal , Internet-delivered intervention improved only 1 of 7 clinical indicators of cardiovascular management in ambulatory post-MI patients BACKGROUND E-learning is a flexible strategy to improve nurses ' knowledge of case management , but there are method ological limitations in previous research into the effectiveness of such programs . PURPOSE To describe the development and effectiveness of an evidence -integrated e-learning program in case management continuing education for Taiwanese psychiatric nurses . DESIGN Multiple methods were adopted to develop the program and a r and omised controlled trial with repeated measures was employed to evaluate it . METHODS The e-learning program was developed in four stages : ( 1 ) systematic review of literature ; ( 2 ) needs assessment through a national survey and focus group ; ( 3 ) development of learning material s ; and ( 4 ) pilot test . Following program development , psychiatric nurses were recruited and r and omly allocated into an experimental or comparison group . The experimental group participated in an e-learning continuing education program . The case management knowledge index with sufficient reliability and validity and a satisfaction survey were used to determine the outcomes . A generalised estimating equation was used to assess the difference between the 2 groups before , after , and at 3 months follow-up . RESULTS The learning material comprised 5 simulated learning modules , self- assessment questions , learning cases , sharing experiences , and learning re sources . A total of 200 participants completed the 3 measurements . Knowledge scores in the experimental group significantly exceeded those in the comparison group after the program and at the 3-month follow-up . Participants reported positive learning perceptions . CONCLUSION The program provides an evidence -based educational re source for nursing continuing education in case management Education on the care of aggressive and disturbed patients is fragmentary . eLearning could ensure the quality of such education , but data on its impact on professional competence in psychiatry are lacking . The aim of this study was to explore the impact of ePsychNurse . Net , an eLearning course , on psychiatric nurses ' professional competence in seclusion and restraint and on their job satisfaction and general self-efficacy . In a r and omized controlled study , 12 wards were r and omly assigned to ePsychNurse . Net ( intervention ) or education as usual ( control ) . Baseline and 3-month follow-up data on nurses ' knowledge of coercion-related legislation , physical restraint and seclusion , their attitudes towards physical restraint and seclusion , job satisfaction and general self-efficacy were analysed for 158 completers . Knowledge ( primary outcome ) of coercion-related legislation improved in the intervention group , while knowledge of physical restraint improved and knowledge of seclusion remained unchanged in both groups . General self-efficacy improved in the intervention group also attitude to seclusion in the control group . In between-group comparison , attitudes to seclusion ( one of secondary outcomes ) favoured the control group . Although the ePsychNurse . Net demonstrated only slight advantages over conventional learning , it may be worth further development with , e.g. flexible time schedule and individualized content OBJECTIVES To determine whether a Web-based educational intervention improves emergency physicians ' knowledge about bioterrorism and to survey physicians ' knowledge and sources of information on bioterrorism . METHODS Prospect i ve r and omized controlled trial using pre- and postintervention testing in hospitals . Participants were general and pediatric emergency medicine attending physicians , fellows , and fourth-year emergency medicine residents . All participants completed a pretest and attended a lecture on bioterrorism . Participants were then r and omized to the Web intervention group that received continuous access to a bioterrorism educational Web site with weekly exposure to case scenarios of diseases due to biological agents , or the control group . Participants were retested after one and six months and surveyed to identify their sources of information and assess their knowledge . RESULTS Sixty-three physicians completed the pretest . There was no difference in mean + /- st and ard deviation ( SD ) pretest scores between Web intervention ( 45 % + /- 10 % ) and control ( 44 % + /- 10 % ) groups ( mean difference : 1.9 % ; 95 % confidence interval [ CI ] = -6.7 % to 2.9 % ) . There was no significant difference between pre- and posttest scores among groups at one month ( Web intervention 48 % + /- 10 % vs. control 45 % + /- 10 % ; mean difference : 3.3 % ; 95 % CI = -8.5 % to 2.0 % ) and six months ( Web intervention 51 % + /- 8 % vs. control 47 % + /- 9 % ; mean difference : 3.8 % ; 95 % CI = -8.8 % to 1.2 % ) . More than 60 % of physicians cited media reports as their primary source of information on bioterrorism and believed that their knowledge of bioterrorism was limited after one month . CONCLUSIONS Providing physicians information on bioterrorism through simulated cases and continuous access to an educational Web site does not increase knowledge of bioterrorism . Physicians are more likely to use media reports for their primary source of information RATIONALE AND OBJECTIVES To examine whether an intervention strategy consisting of a tailored web-based intervention , which provides individualized audit data with peer comparisons and other data that can affect recall , can assist radiologists in setting goals for reducing unnecessary recall . MATERIAL S AND METHODS In a multisite r and omized controlled study , we used a tailored web-based intervention to assess radiologists ' ability to set goals to improve interpretive performance . The intervention provided peer comparison audit data , profiled breast cancer risk in each radiologist 's respective patient population s , and evaluated the possible impact of medical mal practice concerns . We calculated the percentage of radiologists who would consider changing their recall rates , and examined the specific goals they set to reduce recall rates . We describe characteristics of radiologists who developed realistic goals to reduce their recall rates , and their reactions to the importance of patient risk factors and medical mal practice concerns . RESULTS Forty-one of 46 radiologists ( 89.1 % ) who started the intervention completed it . Thirty-one ( 72.1 % ) indicated they would like to change their recall rates and 30 ( 69.8 % ) entered a text response about changing their rates . Sixteen of the 30 ( 53.3 % ) radiologists who included a text response set realistic goals that would likely result in reducing unnecessary recall . The actual recall rates of those who set realistic goals were not statistically different from those who did not ( 13.8 % vs. 15.1 % , respectively ) . The majority of selected goals involved re- review ing cases initially interpreted as Breast Imaging Reporting and Data System category 0 . More than half of radiologists who commented on the influence of patient risk ( 56.3 % ) indicated that radiologists planned to pay more attention to risk factors , and 100 % of participants commented on concerns radiologists have about mal practice with the primary concern ( 37.5 % ) being fear of lawsuits . CONCLUSIONS Interventions design ed to reduce unnecessary recall can succeed in assisting radiologists to develop goals that may ultimately reduce unnecessary recall BACKGROUND Advanced Cardiac Life Support ( ACLS ) is a series of team-based , sequential and time constrained interventions , requiring effective communication and coordination of activities that are performed by the care provider team on a patient undergoing cardiac arrest or respiratory failure . The state-of-the-art ACLS training is conducted in a face-to-face environment under expert supervision and suffers from several drawbacks including conflicting care provider schedules and high cost of training equipment . OBJECTIVE The major objective of the study is to describe , including the design , implementation , and evaluation of a novel approach of delivering ACLS training to care providers using the proposed virtual reality simulator that can overcome the challenges and drawbacks imposed by the traditional face-to-face training method . METHODS We compare the efficacy and performance outcomes associated with traditional ACLS training with the proposed novel approach of using a virtual reality ( VR ) based ACLS training simulator . One hundred and forty-eight ( 148 ) ACLS certified clinicians , translating into 26 care provider teams , were enrolled for this study . Each team was r and omly assigned to one of the three treatment groups : control ( traditional ACLS training ) , persuasive ( VR ACLS training with comprehensive feedback components ) , or minimally persuasive ( VR ACLS training with limited feedback components ) . The teams were tested across two different ACLS procedures that vary in the degree of task complexity : ventricular fibrillation or tachycardia ( VFib/VTach ) and pulseless electric activity ( PEA ) . RESULTS The difference in performance between control and persuasive groups was not statistically significant ( P=.37 for PEA and P=.1 for VFib/VTach ) . However , the difference in performance between control and minimally persuasive groups was significant ( P=.05 for PEA and P=.02 for VFib/VTach ) . The pre-post comparison of performances of the groups showed that control ( P=.017 for PEA , P=.01 for VFib/VTach ) and persuasive ( P=.02 for PEA , P=.048 for VFib/VTach ) groups improved their performances significantly , whereas minimally persuasive group did not ( P=.45 for PEA , P=.46 for VFib/VTach ) . Results also suggest that the benefit of persuasiveness is constrained by the potentially interruptive nature of these features . CONCLUSIONS Our results indicate that the VR-based ACLS training with proper feedback components can provide a learning experience similar to face-to-face training , and therefore could serve as a more easily accessed supplementary training tool to the traditional ACLS training . Our findings also suggest that the degree of persuasive features in VR environments have to be design ed considering the interruptive nature of the feedback elements PURPOSE The purpose of this study was to test the effectiveness of an online problem-based learning ( e-PBL ) program that offers multimedia scenarios to develop sexual health care competencies . METHOD A pretest – posttest control group design was used with two r and omized groups in one Korean tertiary hospital . The sample included 32 RNs who cared for oncology patients . The intervention group completed an e-PBL cycle consisting of eight tutorials . RESULTS Nurses in the intervention group scored significantly higher on knowledge than did those in the control group . The intervention group exhibited no significant differences in attitude and practice s following the intervention . CONCLUSION The results show the potential of e-PBL to enhance traditional PBL by offering multimedia scenarios in an interactive and flexible learning environment Web-based learning provides educational opportunities for students who are independent and self-directed . While the complexities of educational outcomes of web-based learning have not yet been completely documented , further studies are required using rigorous research design techniques to study the outcomes of web-based learning as compared to traditional face-to-face learning . The purpose s of this study were to : ( 1 ) assess the learner outcomes of web-based learning as compared to face-to-face learning group , and ( 2 ) explore methods that maximize the use of web-based learning for continuing nursing education . A r and omized controlled trial of web-based learning in comparison to face-to-face lectures for registered nurses or midwives was conducted . One hundred and one nurses and midwives were eligible to participate and 93 were r and omized , 45 for the web-based learning and 48 for the face-to face group . Thirty-seven ( 82.2 % ) completed the web-based learning and 33 ( 68.8 % ) the face-to-face program . There was no difference in the post-test scores between the web-based learning group ( mean=76.2 ) and the face-to-face learning group ( mean=79.4 ) ( t=0.66 , df=68 , p=0.51 ) . There were three distinct advantages to the web-based group , even though both group demonstrated the same learning outcomes . First the dropout rate was lower in the web-based program . Second the flexibility of web-based learning was reported by several participants . Finally , web-based learning was attractive to an affordable for a wide age range of the nurses PURPOSE This study analyzed the effects of a blended learning program on medication administration by new nurses using a non-equivalent groups design . METHOD A medication education program using blended learning ( including e-learning ) was administered to 26 new nurses , while face-to-face instruction in the classroom was given to 24 new nurses . The following dependent variables were compared : degree of knowledge of medication , self-efficacy of medication administration , medication-administration ability , and satisfaction with the learning program . RESULTS The experimental , blended learning group showed a significantly higher level of knowledge of medication and satisfaction with the comprehensiveness of their medication learning , but the self-efficacy of medication administration , medication-administration ability , and other items related to their learning satisfaction did not differ significantly from that in the control group . CONCLUSION These results suggest that blended learning integrating e-learning and face-to-face instruction in the classroom is useful for enhancing medication knowledge . An e-learning program can reduce the lecturing time and cost of repeated topics such as medication , suggesting that it can be an effective component in nurse education programs BACKGROUND Low Chlamydia trachomatis screening rates create an opportunity to test innovative continuing medical education ( CME ) programs . Few studies of Internet-based physician learning have been evaluated with objective data on practice patterns . DESIGN This r and omized controlled trial tested a multicomponent Internet CME ( mCME ) intervention for increasing chlamydia screening of at-risk women aged 16 to 26 years . SETTING Eligible physician offices had > or = 20 patients at risk for chlamydia as defined by the Health Plan Employer Data and Information Set ( HEDIS ) , had at least one primary care physician ( internal medicine , family medicine/general practice , pediatrics ) with Internet access , and participated in the study managed care organization . The 191 r and omized primary care offices represented 20 states . INTERVENTION The intervention , available from February to December 2001 , consisted of four case-based learning modules , was tailored in real time to each physician based on theory of behavior change , and included office-level feedback of chlamydia screening rates . MAIN OUTCOME MEASURE HEDIS chlamydia screening rates for the pre-intervention ( 2000 ) and post-intervention ( 2002 ) periods . RESULTS Pre-intervention screening rates for the intervention and comparison offices were 18.9 % and 16.2 % ( p = 0.135 ) . Post-intervention screening rates for the intervention and comparison offices were 15.5 % and 12.4 % , respectively ( p = 0.044 , adjusting for baseline performance ) . CONCLUSIONS The substantial decline in chlamydia screening rates observed in the comparison offices was significantly attenuated for the intervention offices . The mCME favorably influenced chlamydia screening by primary care physicians The purpose of this study was to evaluate the potential for online continuing medical education ( CME ) seminars to improve quality of care . Primary care physicians ( 113 ) participated in a r and omized controlled trial to evaluate an online CME series . Physicians were r and omized to view either a seminar about type 2 diabetes or a seminar about systolic heart failure . Following the seminar , physicians were presented with 4 clinical vignettes and asked to describe what tests , treatments , counseling , or referrals they would recommend . Physicians who viewed the seminars were significantly more likely to recommend guideline -consistent care to patients in the vignettes . For example , physicians who viewed the diabetes seminar were significantly more likely to order an eye exam for diabetes patients ( 63 % ) compared with physicians in the control group ( 27 % ) . For some guidelines there were no group differences . These results provide early evidence of the effectiveness of online CME programs to improve physician clinical practice . ( Am J Med Qual 2008;23:475 - 483 Introduction : Chronic kidney disease ( CKD ) patients are multimorbid elderly at high risk of drug‐related problems . A Web‐based training program was developed based on a list of significant drug‐related problems in CKD patients requiring a pharmaceutical intervention . The objectives were to evaluate the impact of the program on community pharmacists ' knowledge and skills and their satisfaction with the training . Methods : Pharmacists were r and omized to the training program or the control group . Training comprised a 60‐minute Web‐based interactive session supported by a clinical guide . Pharmacists completed a question naire on knowledge ( 10 multiple‐choice questions ) and skills ( 2 clinical vignettes ) at baseline and a second time within 1 month . Trained pharmacists completed a written satisfaction question naire . Semidirected telephone interviews were conducted with 8 trained pharmacists . Changes in knowledge and skills scores were compared between the groups . Results : Seventy pharmacists ( training : 52 ; control : 18 ) were recruited ; the majority were women with < 15 years ' experience . Compared with the control group , an adjusted incremental increase in the knowledge score ( 22 % ; 95 % confidence interval [ CI ] : 16%‐27 % ) and skills score ( 24 % ; 95 % CI : 16%‐33 % ) was observed in the training group . Most pharmacists ( 87%‐100 % ) rated each aspect of the program “ excellent ” or “ very good . ” Additional training and adding a discussion forum were suggested to complement the program . Discussion : Pharmacists like the Web‐based continuing education program . Over a short time span , the program improved their knowledge and skills . Its impact on their clinical practice s and quality of medication use in CKD patients remains to be assessed Purpose Herbs and dietary supplements are widely used , and there is an urgent need to educate health professionals about their risks and benefits . The Internet provides an innovative way of educating busy health professionals . This study assessed the impact of an Internet-based curriculum on health professionals ' knowledge , confidence , and clinical practice s related to herbs and dietary supplements . Method The study was a r and omized crossover trial involving physicians , pharmacists , advanced practice nurses , and dietitians . Participants were invited by e-mail and r and omly assigned to immediate intervention versus waiting-list groups ( n = 537 ) . The curriculum lasted ten weeks and consisted of 20 case-based modules , each involving one multiple-choice or true-or-false question and its answer , links to reliable Internet sources of additional information , and a moderated listserv discussion group . Participants were surveyed about their knowledge , confidence , and communication related to herbs and dietary supplements on enrollment , after the immediate intervention group had completed the curriculum , and after the waiting-list group completed the curriculum . Results Baseline scores for knowledge , confidence , and communication were similar in the two groups . At the first follow-up , there was greater improvement in scores for all three areas in the immediate intervention group than in the waiting-list group ( improvement for knowledge , 3.0 versus 1.4 ; confidence , 2.6 versus 0.6 ; communication , 0.21 versus −0.1 , p < .01 for all comparisons ) . After all participants had received the curriculum , scores for both groups were significantly better than at baseline and similar to one another . Conclusion Internet-based education about herbs and dietary supplements for diverse health professionals is feasible and results in significant and sustained improvements in knowledge , confidence , and communication practice Purpose To compare the educational effectiveness of two virtual patient (VP)-based e-learning strategies , versus no training , in improving physicians ’ substance abuse management knowledge , attitudes , self-reported behaviors , and decision making . Method The 2011–2012 study was a posttest-only , three-arm , r and omized controlled trial in 90 resident and 30 faculty physicians from five adult medicine primary care training programs . The intervention was one of two 2-hour VP-based e-learning programs , design ed by national experts to teach structured screening , brief interventions , referral , and treatment skills . One used traditional problem solving with feedback ( unworked example ) , and the other incorporated an expert demonstration first , followed by problem solving with feedback ( worked example ) . The main outcome measure was performance on the Physicians ’ Competence in Substance Abuse Test ( P-CSAT , maximum score = 315 ) , a self-administered , previously vali date d measure of physicians ’ competence in managing substance abuse . The survey was completed at the outset of the study and two months later . Results Overall P-CSAT scores were virtually identical ( 202–211 , P > .05 ) between both intervention groups and the no-training control group at both times . Average faculty P-CSAT scores ( 221.9 , 224.6 ) were significantly higher ( P < .01 ) than resident scores ( 203.7 , 202.5 ) at both times . Conclusions This study did not provide evidence that a brief , worked example , VP-based e-learning program or a traditional , unworked , VP-based e-learning program was superior to no training in improving physicians ’ substance abuse management skills . The study did provide additional evidence that the P-CSAT distinguishes between physicians who should possess different levels of substance abuse management skills Background Mammography is considered the best imaging technique for breast cancer screening , and the radiographer plays an important role in its performance . Therefore , continuing education is critical to improving the performance of these professionals and thus providing better health care services . Objective Our goal was to develop an e-learning course on breast imaging for radiographers , assessing its efficacy , effectiveness , and user satisfaction . Methods A stratified r and omized controlled trial was performed with radiographers and radiology students who already had mammography training , using pre- and post-knowledge tests , and satisfaction question naires . The primary outcome was the improvement in test results ( percentage of correct answers ) , using intention-to-treat and per- protocol analysis . Results A total of 54 participants were assigned to the intervention ( 20 students plus 34 radiographers ) with 53 controls ( 19 + 34 ) . The intervention was completed by 40 participants ( 11 + 29 ) , with 4 ( 2 + 2 ) discontinued interventions , and 10 ( 7 + 3 ) lost to follow-up . Differences in the primary outcome were found between intervention and control : 21 versus 4 percentage points ( pp ) , P<.001 . Stratified analysis showed effect in radiographers ( 23 pp vs 4 pp ; P=.004 ) but was unclear in students ( 18 pp vs 5 pp ; P=.098 ) . Nonetheless , differences in students ’ posttest results were found ( 88 % vs 63 % ; P=.003 ) , which were absent in pretest ( 63 % vs 63 % ; P=.106 ) . The per- protocol analysis showed a higher effect ( 26 pp vs 2 pp ; P<.001 ) , both in students ( 25 pp vs 3 pp ; P=.004 ) and radiographers ( 27 pp vs 2 pp ; P<.001 ) . Overall , 85 % were satisfied with the course , and 88 % considered it successful . Conclusions This e-learning course is effective , especially for radiographers , which highlights the need for continuing education Background The diagnosis of displacement in scaphoid fractures is notorious for poor interobserver reliability . Questions / purpose sWe tested whether training can improve interobserver reliability and sensitivity , specificity , and accuracy for the diagnosis of scaphoid fracture displacement on radiographs and CT scans . Methods Sixty-four orthopaedic surgeons rated a set of radiographs and CT scans of 10 displaced and 10 nondisplaced scaphoid fractures for the presence of displacement , using a web-based rating application . Before rating , observers were r and omized to a training group ( 34 observers ) and a nontraining group ( 30 observers ) . The training group received an online training module before the rating session , and the nontraining group did not . Interobserver reliability for training and nontraining was assessed by Siegel ’s multirater kappa and the Z-test was used to test for significance . Results There was a small , but significant difference in the interobserver reliability for displacement ratings in favor of the training group compared with the nontraining group . Ratings of radiographs and CT scans combined result ed in moderate agreement for both groups . The average sensitivity , specificity , and accuracy of diagnosing displacement of scaphoid fractures were , respectively , 83 % , 85 % , and 84 % for the nontraining group and 87 % , 86 % , and 87 % for the training group . Assuming a 5 % prevalence of fracture displacement , the positive predictive value was 0.23 in the nontraining group and 0.25 in the training group . The negative predictive value was 0.99 in both groups . Conclusions Our results suggest training can improve interobserver reliability and sensitivity , specificity and accuracy for the diagnosis of scaphoid fracture displacement , but the improvements are slight . These findings are encouraging for future research regarding interobserver variation and how to reduce it further & NA ; The aim of this study was to describe registered nurses ' experiences with an e-learning education program ( ELEP ) conducted at a 776-bed teaching medical center in Taipei . The study was completed in three stages : planning , implementation , and evaluation . Nurses who were registered were r and omly assigned either to the ELEP or traditional in-classroom program ( TICP ) . Data were analyzed using descriptive and inferential statistics . Forty-two nurses participated ( 22 in the ELEP and 20 in the TICP ) . Scores for participants were all > 70 points ( out of 100 ) for both programs . Of the five courses , only teaching and learning and communication showed significant statistical difference between the two groups ( p = .001 ) . Nearly all participants ( 97.6 % ) felt satisfied with their program ( both ELEP and TICP ) . All nurses passed the nursing care skill tests . Findings should help guide efforts to popularize e-learning education in Taiwan and help create alternative learning methods for future continuing nursing education programs Summary BACKGROUND Increased clinical dem and s and decreased available time accentuate the need for efficient learning in postgraduate medical training . Adapting Web-based learning ( WBL ) to learners ’ prior knowledge may improve efficiency . OBJECTIVE We hypothesized that time spent learning would be shorter and test scores not adversely affected for residents who used a WBL intervention that adapted to prior knowledge . DESIGN R and omized , crossover trial . SETTING Academic internal medicine residency program continuity clinic . PARTICIPANTS 122 internal medicine residents . INTERVENTIONS Four WBL modules on ambulatory medicine were developed in st and ard and adaptive formats . The adaptive format allowed learners who correctly answered case-based questions to skip the corresponding content . MEASUREMENTS and Main Results The measurements were knowledge posttest , time spent on modules , and format preference . One hundred twenty-two residents completed at least 1 module , and 111 completed all 4 . Knowledge scores were similar between the adaptive format ( mean ± st and ard error of the mean , 76.2 ± 0.9 ) and st and ard ( 77.2 ± 0.9 , 95 % confidence interval [ CI ] for difference −3.0 to 1.0 , P = .34 ) . However , time spent was lower for the adaptive format ( 29.3 minutes [ CI 26.0 to 33.0 ] per module ) than for the st and ard ( 35.6 [ 31.6 to 40.3 ] ) , an 18 % decrease in time ( CI 9 to 26 % , P = .0003 ) . Seventy-two of 96 respondents ( 75 % ) preferred the adaptive format . CONCLUSIONS Adapting WBL to learners ’ prior knowledge can reduce learning time without adversely affecting knowledge scores , suggesting greater learning efficiency . In an era where reduced duty hours and growing clinical dem and s on trainees and faculty limit the time available for learning , such efficiencies will be increasingly important . For clinical trial registration , see http://www . clinical trials.gov NCT00466453 ( http://www . clinical trials.gov/ct/show/NCT00466453?order=1 ) OBJECTIVE Determine whether lectures by national experts and a publicly available online program with similar educational objectives can improve knowledge , attitudes , and beliefs ( KAB ) important to chronic pain management . DESIGN A pretest-posttest r and omized design with two active educational interventions in two different physician groups and a third physician group that received live education on a different topic to control for outside influences , including retesting effects , on our evaluation . PARTICIPANTS A total of 136 community-based primary care physicians met eligibility criteria . All physicians attended the educational program to which they were assigned . Ninety-five physicians ( 70 % ) provided complete data for evaluation . MEASUREMENTS Physician responses to a st and ardized 50-item pain management KAB survey before , immediately after , and 3 months following the interventions . RESULTS The study groups and the 41 physicians not providing outcomes information were similar with respect to age , sex , race , percent engaged in primary care , and number of patients seen per week . Physician survey scores improved immediately following both pain education programs ( live : 138.0 - ->150.6 , P < 0.001 ; online : 143.6 - ->150.4 , P = 0.007 ) , but did not change appreciably in the control group ( 139.2 - ->142.5 , P > 0.05 ) . Findings persisted at 3 months . Satisfaction measures were high ( 4.00 - 4.72 on 1 - 5 scale ) and not significantly different ( P = 0.072 - 0.893 ) between groups . CONCLUSIONS When used under similar conditions , national speakers and a publicly available online CME program were associated with improved pain management KAB in physicians . The benefits lasted for 3 months . These findings support the continued use of these pain education strategies OBJECTIVE The evaluation and training of raters who conduct efficacy evaluations in clinical trials is an important method ological variable that is often overlooked . Few rater training programs focus on teaching and assessing applied clinical skills , and even fewer have been empirically examined for efficacy . The goal of this study was to develop a comprehensive , st and ardized , interactive rater training program using new technologies , and to compare the relative effectiveness of this approach to " traditional " rater training in a multi-center clinical trial . METHOD 12 sites from a 22 site multi-center study were r and omly selected to participate ( 6=traditional , 6=enriched ) . Traditional training consisted of an overview of scoring conventions , watching and scoring videotapes with discussion , and observation of interviews in small groups with feedback . Enriched training consisted of an interactive web tutorial , and live , remote observation of trainees conducting interviews with real or st and ardized patients , via video- or teleconference . Outcome measures included a didactic exam on conceptual knowledge and blinded ratings of trainee 's audiotaped interviews . RESULTS A significant difference was found between enriched and traditional training on pre-to-post training improvement on didactic knowledge , t(27)=4.2 , p<0.0001 . Enriched trainees clinical skills also improved significantly more than traditional trainees , t(56)=2.1 , p=0.035 . All trainees found the applied training helpful , and wanted similar web tutorials with other scales . CONCLUSIONS Results support the efficacy of enriched rater training in improving both conceptual knowledge and applied skills . Remote technologies enhance training efforts , and make training accessible and cost-effective . Future rater training efforts should be subject to empirical evaluation , and include training on applied skills Objective To evaluate the effectiveness of an electronic learning ( e-learning ) programme on the performance of nurses in the recognition of child abuse in a simulated case in the Emergency Department ( ED ) . Design Blinded , r and omised controlled trial using pre- and postintervention design . Setting The ED of a University Medical Center in the Netherl and s. Participants 38 ED nurses were included , 25 nurses were analysed . Intervention Half of the participants followed a 2-h e-learning programme focused on the recognition of child abuse , the others acted as a control group . Main outcome measurements Individual performance during a case-simulated parent interview to detect child abuse and self-reported self-efficacy for the detection of child abuse . Performance on the simulation was scored by an expert panel using a st and ardised assessment form which was design ed to score quantity and quality of the questions posed by the nurse ( minimum score 0 ; maximum score 114 ) . Results During post-test , nurses in the intervention group performed significantly better during the simulation than the control group , ( 89 vs 71 , 95 % CI 2.9 to 33.3 ) , and reported higher self-efficacy ( 502 vs 447 , 95 % CI −25.4 to 134.7 ) . Performance in detecting child abuse correlated positively with the self-efficacy score ( Spearman correlation 0.387 , p value 0.056 ) . Comparing post- and pretest results separately for the intervention and the control group showed a significant increase in performance in the intervention group . Conclusion E-learning improved the performance in case simulations and the self-efficacy of the nurses in the ED in the detection of child abuse . Wider implementation of the e-learning programme to improve the first step in the detection of child abuse is recommended . Trial registration Protocol registration system of clinical trials.gov : OBJECTIVE This study was design ed to investigate the efficacy of a web-based mental disorder stigma education program for mental health professionals . METHODS The sample consisted of 205 individuals who were either residents or specialists in psychiatry . Participants were contacted through a national web-based e-mail group that consisted of professionals in psychiatry , who were r and omly assigned to experimental and control groups . The experimental group received an informative e-mail which contained a general account of " stigma " before they were asked to respond to an Internet-based question naire which was design ed to predict their stigmatizing attitudes towards individuals with mental disorders . Control subjects , on the other h and , were asked to respond to the same Internet-based question naire without having been given the aforementioned informative e-mail . RESULTS The experimental group , compared to the control group , demonstrated a lesser stigmatizing attitude towards individuals with mental illness , as measured by the Internet-based survey which utilized the " social distance " concepts of stigma . CONCLUSIONS These data suggest that such " anti-stigma " campaigns using the potential of the Internet might be an effective tool in the fight against the stigmatization of persons with mental illness Objectives . To assess provider acceptability of a distance learning program for pediatric asthma and pilot test its effects on physician knowledge , attitudes and treatment practice s. Design . R and omized controlled trial . Setting . Louisville and the surrounding central Kentucky region . Participants . Twenty-four pediatricians in clinical practice . Interventions . A distance learning program for pediatric asthma consisting of Web- or CD-ROM – based multimedia learning modules and two teleconference calls . Outcome Measures . Learner satisfaction and change in physician asthma knowledge , attitudes , and treatment behavior at 1 to 4 months ( short term ) and 6 to 8 months ( long term ) . Results . Pediatricians had graduated from medical school a mean of 11.6 years before baseline ( SD ±8.9 ) ; 56 % were female . On all learner satisfaction items , the average score was a 4.0 or greater on a 5-point scale , indicating a favorable response from the participants . Participants in the education group reported increased familiarity with asthma guideline for prescribing daily-inhaled corticosteroids compared to control physicians ( p = .03 ) at short-term follow-up . Participants also expressed increased confidence in selecting a medicine for patients requiring a low-dose inhaled steroid ( p = .03 ) . However , these differences were not seen at long-term follow-up . Compared to the control group , there was no significant increase in the proportion of patients receiving inhaled steroids for persistent asthma at short- or long-term follow-up . Conclusions . Pediatricians utilizing an asthma distance learning program expressed a high degree of learner satisfaction . The program was associated with a temporary increase in familiarity and confidence in implementing components of the asthma guidelines OBJECTIVES /HYPOTHESIS To compare the pass rate of residents performing the Particle Repositioning Maneuver ( PRM ) after one of three interventions : 1 ) small group PRM instruction ( SG ) ; 2 ) st and ard classroom instruction ( CI ) ; and 3 ) Web-based learning module ( WM ) . We hypothesize that our Web-based learning module is more effective than CI and as effective as SG . STUDY DESIGN Prospect i ve r and omized control trial . METHODS The study population includes all family medicine residents at the University of Western Ontario . On day 0 , all subjects were tested . Residents were then r and omized to one of three intervention groups : 1 ) SG , 2 ) CI , or 3 ) WM . On day 7 , the residents were again tested . Observers were blinded to the intervention type . Testing ( day 0 and day 7 ) was performed using the DizzyFIX ( Clearwater Clinical Ltd. , London , Ontario , Canada ) , a pass/fail test , and evaluation by a trained observer ( correct or incorrect ) . RESULTS There were no statistically significant differences in pass rates between the three groups before the interventions ( DizzyFIX : P = .2096 , observer : P = .3710 ) . After the interventions , DizzyFIX testing pass rates were 50.0 % SG , 60.0 % CI and 100.0 % WM ( P = .3564 ) . Observer testing pass rates were 85.7 % SG , 28.6 % CI , and 83.3 % WM ( P = .0431 ) . CONCLUSIONS This study demonstrated that our Web-based learning module for the PRM is comparable to small-group clinical instruction , and superior to st and ard classroom instruction for teaching the PRM when evaluated by a trained observer BACKGROUND R and omized studies examining the effect of training of mental health professionals in suicide prevention guidelines are scarce . We assessed whether professionals benefited from an e-learning supported Train-the-Trainer programme aim ed at the application of the Dutch multidisciplinary suicide prevention guideline . METHODS 45 psychiatric departments from all over the Netherl and s were clustered in pairs and r and omized . In the experimental condition , all of the staff of psychiatric departments was trained by peers with an e-learning supported Train-the-Trainer programme . Guideline adherence of individual professionals was measured by means of the response to on-line video fragments . Multilevel analyses were used to establish whether variation between conditions was due to differences between individual professionals or departments . RESULTS Multilevel analysis showed that the intervention result ed in an improvement of individual professionals . At the 3 month follow-up , professionals who received the intervention showed greater guideline adherence , improved self-perceived knowledge and improved confidence as providers of care than professionals who were only exposed to traditional guideline dissemination . Subgroup analyses showed that improved guideline adherence was found among nurses but not among psychiatrists and psychologists . No significant effect of the intervention on team performance was found . LIMITATIONS The ICT environment in departments was often technically inadequate when displaying the video clips clip of the survey . This may have caused considerable drop-out and possibly introduced selection bias , as professionals who were strongly affiliated to the theme of the study might have been more likely to finish the study . CONCLUSIONS Our results support the idea that an e-learning supported Train-the-Trainer programme is an effective strategy for implementing clinical guidelines and improving care for suicidal patients . TRIAL REGISTRATION Netherl and s Trial Register ( NTR3092 www.trialregister.nl ) BACKGROUND AND OBJECTIVES Primary care physicians ( PCPs ) are uniquely positioned to detect melanoma . Effective educational interventions targeted at PCPs may improve early melanoma detection . A previous in-person Basic Skin Cancer Triage ( BSCT ) 2-hour course demonstrated significant short-term improvement in provider practice s , attitudes , ability , confidence , and knowledge . We conducted a r and omized trial to test the efficacy of the BSCT course implemented as a web-based learning program , compared to a similar ( control ) web-based course on weight assessment . METHODS We recruited a sample of 57 PCPs and 3,341 of their patients from four geographically diverse centers . Skin cancer control activities by PCPs were assessed by physician survey and by chart review and patient telephone interview about their recent visit to their PCP at baseline and at 1 - -2 months and 12 months after course completion . RESULTS Some effect of intervention on skin cancer parameters was self-reported by physicians ; this was not confirmed by patient survey or chart-extracted data . Rates of skin cancer control practice s by PCPs were low across both groups before and after intervention . The positive changes in physician-reported behaviors ( total body skin examination [ TBSE ] ) , intentions ( discuss skin cancer detection ) , confidence ( performing TBSE ) , office practice s , and knowledge ( 58 % skin versus 49 % control ) were neither matched by differences in practice reported by their patients , nor persisted in a longer term follow-up , hence may be attributable to physician recall bias due to the experience of the course or desire to please study investigators and were less dramatic as compared to our previously reported in-person BSCT intervention . Thus this approach by itself appears unlikely to result in improved PCP h and ling of skin cancer issues . CONCLUSIONS Given previous success with our in-person course , the features required to make WBL a more effective tool for medical education must be further explored Purpose To investigate the association between physician participants ' levels of engagement in a Web-based educational intervention and their patients ' baseline diabetes measures . Method The authors conducted a r and omized trial of online CME activities design ed to improve diabetes care provided by family , general , and internal medicine physicians in rural areas of 11 southeastern states between September 2006 and July 2008 . Using incidence rate ratios derived from negative binomial models , the relationship between physicians ' engagement with the study Web site and baseline proportion of their patients having controlled diabetes ( hemoglobin A1c ≤7 % ) was explored . Results One hundred thirty-three participants ( intervention = 64 ; control = 69 ) provided information for 1,637 patients with diabetes . In the intervention group , physicians in practice s in the worst quartiles of A1c control were least engaged with the study Web site in nearly all dimensions . Total number of pages viewed decreased as quartile of A1c control worsened ( 137 , 73 , 68 , 57 ; P = .007 ) ; similarly , for a given 10 % increase in proportion of patients with controlled A1c , participants viewed 1.13 times more pages ( 95 % CI : 1.02–1.26 , P = .02 ) . In the control group , engagement was neither correlated with A1c control nor different across quartiles of A1c control . Conclusions Engagement in Web-based interventions is measurable and has important implication s for research and education . Because physicians of patients with the greatest need for improvement in A1c control may not use online educational re sources as intensely as others , other strategies may be necessary to engage these physicians in professional development activities PURPOSE Radiation oncologists are faced with the challenge of irradiating tumors to a curative dose while limiting toxicity to healthy surrounding tissues . This can be achieved only with superior knowledge of radiologic anatomy and treatment planning . Educational re sources design ed to meet these specific needs are lacking . A web-based interactive module design ed to improve residents ' knowledge and application of key anatomy concepts pertinent to radiotherapy treatment planning was developed , and its effectiveness was assessed . METHODS AND MATERIAL S The module , based on gynecologic malignancies , was developed in collaboration with a multidisciplinary team of subject matter experts . Subsequently , a multi-centre r and omized controlled study was conducted to test the module 's effectiveness . Thirty-six radiation oncology residents participated in the study ; 1920 were granted access to the module ( intervention group ) , and 17 in the control group relied on traditional methods to acquire their knowledge . Pretests and posttests were administered to all participants . Statistical analysis was carried out using paired t test , analysis of variance , and post hoc tests . RESULTS The r and omized control study revealed that the intervention group 's pretest and posttest mean scores were 35 % and 52 % , respectively , and those of the control group were 37 % and 42 % , respectively . The mean improvement in test scores was 17 % ( p < 0.05 ) for the intervention group and 5 % ( p = not significant ) for the control group . Retrospective pretest and posttest surveys showed a statistically significant change on all measured module objectives . CONCLUSIONS The use of an interactive e-learning teaching module for radiation oncology is an effective method to improve the radiologic anatomy knowledge and treatment planning skills of radiation oncology residents Introduction : Opioid misuse is common among patients with chronic nonmalignant pain . There is a pressing need for physicians to increase their confidence and competence in managing these patients . Methods : A r and omized controlled trial of family physicians ( N = 88 ) attending 1 of 4 continuing medical education events helped to determine the effectiveness of e‐mail case discussion s in changing physician behavior . Before r and om assignment , participants completed a pretest and attended a 3‐hour didactic session on prescribing opioids and benzodiazepines . The intervention group participated in 10 weeks of e‐mail case discussion s , with design ated participants responding to questions on cases . An addictions physician facilitated the discussion . Several months after the e‐mail discussion , participants took part in a mock telephone consultation ; a blinded research er posing as a medical colleague asked for advice about 2 cases involving opioid and benzodiazepine prescribing . Using a checklist , the research er recorded the questions asked and advice given by the physician . Results : On post‐testing , both groups expressed greater optimism about treatment outcomes and were more likely to report using a treatment contract and providing advice about sleep hygiene . There were no significant differences between pretesting and post‐testing between the groups on the survey . During the telephone consultation , the intervention group asked significantly more questions and offered more advice than the control group ( odds ratio for question items , 1.27 [ p = .03 ] ; advice items , 1.33 [ p = .01 ) . Discussion : Facilitated by electronic mail and a medical expert , case discussion is an effective means of improving physician performance . Telephone consultation holds promise as a method for evaluating physicians ' assessment and management skills OBJECTIVE To determine the efficacy of an Internet-based skin cancer triage intervention for physicians . METHODS Physicians were r and omly assigned to an intervention group or a control group . The 14 outcome measures included diagnosis and evaluation planning for malignant melanoma , basal cell carcinoma , and squamous cell carcinoma . RESULTS Forty-six physicians ( 27 of 39 in the intervention group ) completed the program . The intervention group scored significantly higher than did the control group in nine of 14 outcome measures ; this improvement was maintained for five of the nine outcomes . CONCLUSION The Internet intervention improved physicians ' skin cancer diagnosis and evaluation planning test performances This study evaluated the efficacy of methods of training community mental health providers ( N=132 ) in dialectical behavior therapy ( DBT ) distress tolerance skills , including ( a ) Linehan 's ( 1993a ) Skills Training Manual for Borderline Personality Disorder ( Manual ) , ( b ) a multimedia e-Learning course covering the same content ( e-DBT ) , and ( c ) a placebo control e-Learning course ( e-Control ) . Participants were r and omized to a condition , and the training took place in a highly structured and controlled learning environment . Assessment s were completed at baseline , post-training , and 2 , 7 , 11 , and 15 weeks following training . The results indicate that one or both of the active DBT conditions outperformed the control condition on all outcomes except motivation to learn and use the treatment . While clinicians preferred e-DBT over the Manual and found it more helpful and engaging , the active DBT conditions generally did not differ on the primary outcomes of knowledge and self-efficacy , with the exception that e-DBT significantly outperformed the Manual on knowledge at the 15-week follow-up . E-DBT also produced the highest rate of applying and teaching the newly learned skills in clinical practice . Overall , results from this study support the efficacy of e-Learning in disseminating knowledge of empirically supported treatments to clinicians , while also indicating that treatment manuals can be effective training tools OBJECTIVE To assess the strength of causal inferences reported in r and omized and nonr and omized evaluations of quality improvement ( QI ) interventions in relation to the study design and the direction of results for the primary outcomes . STUDY DESIGN AND SETTING We search ed 11 journals for QI intervention studies that aim ed to change clinician behavior . Statements that addressed the causal inference between intervention and outcomes were extracted and were rated by 34 research ers for the strength of causality . RESULTS We found 38 r and omized controlled trials ( RCTs ) and 35 non- RCTs , and extracted 68 quotes from the abstract s and 139 from the main text . A significant interaction was found between study design and direction of results for the abstract quotes ( P=0.022 ) . The ratings for non- RCTs were higher when the results were mixed , but for RCTs , they were higher if the results were positive or no effect , although none of the differences were statistically significant at alpha=0.05 after adjusting for multiple comparisons . For the main text quotes , the causality rating was higher by 0.43 for RCTs than for non- RCTs after adjusting for the direction of results ( P<0.001 ) . CONCLUSION Authors might have overstated the strength of causal inference in the abstract s of non- RCTs , but appeared to report causality appropriately in the main text OBJECTIVE To determine the effectiveness of a provider-based education and implementation intervention for improving diabetes control . DESIGN Cluster-r and omized trial with baseline and follow-up cross sections of diabetes patients in each participating physician 's practice . SETTING Eleven US Southeastern states , 2006 - 08 . PARTICIPANTS Two hundred and five rural primary care physicians . INTERVENTION Multi-component interactive intervention including Web-based continuing medical education , performance feedback and quality improvement tools . Primary Outcome Measures ' Acceptable control ' [ hemoglobin A1c ≤9 % , blood pressure ( BP ) < 140/90 mmHg , low-density lipoprotein cholesterol ( LDL ) < 130 mg/dl ] and ' optimal control ' ( A1c < 7 % , BP < 130/80 mmHg , LDL < 100 mg/dl ) . RESULTS Of 364 physicians attempting to register , 205 were r and omized to the intervention ( n= 102 ) or control arms ( n= 103 ) . Baseline and follow-up data were provided by 95 physicians ( 2127 patients ) . The proportion of patients with A1c ≤9 % was similar at baseline and follow-up in both the control [ adjusted odds ratio ( AOR ) : 0.94 ; 95 % confidence interval ( CI ) : 0.61 , 1.47 ] and intervention arms [ AOR : 1.16 ( 95 % CI : 0.80 , 1.69 ) ] ; BP < 140/90 mmHg and LDL < 130 mg/dl were also similar at both measurement points ( P= 0.66 , P= 0.46 ; respectively ) . We observed no significant effect on diabetes control attributable to the intervention for any of the primary outcome measures . Intervention physicians engaged with the Website over a median of 64.7 weeks [ interquartile range ( IQR ) : 45.4 - 81.8 ) for a median total of 37 min ( IQR : 16 - 66 ) . CONCLUSIONS A wide-reach , low-intensity , Web-based interactive multi-component intervention did not improve control of glucose , BP or lipids for patients with diabetes of physicians practicing in the rural Southeastern US AIM To evaluate the effect of an educational intervention among primary care physicians on several indicators of good clinical practice in diabetes care . METHODS Two groups of physicians were r and omly assigned to the intervention or control group ( IG and CG ) . Every physician r and omly selected two sample s of patients from all type 2 diabetic patients aged 40 years and above and diagnosed more than a year ago . Baseline and final information were collected cross-sectionally 12 months apart , in two independent sample s of 30 patients per physician . The educational intervention comprised : distribution of educational material s and physicians ' specific bench-marking information , an on-line course and three on-site educational workshops on diabetes . External observers collected information directly from the physicians and from the medical records of the patients on personal and family history of disease and on the evolution and treatment of their disease . Baseline information was collected retrospectively in the control group . RESULTS Intervention group comprised 53 physicians who included a total of 3018 patients in the baseline and final evaluations . CG comprised 50 physicians who included 2868 patients in the same evaluations . Measurement of micro-albuminuria in the last 12 months ( OR = 1.6 , 95 % CI : 1.1 - 2.4 ) and foot examination in the last year ( OR = 2.0 , 95 % CI : 1.1 - 3.6 ) were the indicators for which greater improvement was found in the IG . No other indicator considered showed statistically significant improvement between groups . CONCLUSIONS The identification of indicators with very low level of compliance and the implementation of a simple intervention in physicians to correct them is effective in improving the quality of care of diabetic patients Background : Spaced education ( SE ) is a novel , evidence ‐based form of online learning . We investigated whether an SE program following a face‐to‐face continuing medical education ( CME ) course could enhance the course 's impact on providers ' clinical behaviors . Methods : This r and omized controlled trial was conducted from March 2009 to April 2010 , immediately following the Current Clinical Issues in Primary Care ( Pri‐Med ) CME conference in Houston , Texas . Enrolled providers were r and omized to receive the SE program immediately after the live CME event or 18 weeks later ( wait‐list controls ) . The SE program consisted of 40 vali date d questions and explanations covering 4 clinical topics . The repetition intervals were adapted to each provider based on his or her performance ( 8‐ and 16‐day intervals for incorrect and correct answers , respectively ) . Questions were retired when answered correctly twice in a row . At week 18 , a behavior change survey instrument was administered simultaneously to providers in both cohorts . Results : Seventy‐four percent of participants ( 181/246 ) completed the SE program . Of these , 97 % ( 176/181 ) su bmi tted the behavior change survey . Across all 4 clinical topics , providers who received SE reported significantly greater change in their global clinical behaviors as a result of the CME program ( p‐values .013 to < .001 ; effect size 0.7 ) . Ninety‐seven percent ( 175/179 ) requested to participate in future SE supplements to live CME courses . Eighty‐six percent ( 156/179 ) agreed or strongly agreed that the SE program enhanced the impact of the live CME conference . Discussion : Online spaced education following a live CME course can significantly increase the impact of a face‐to‐face course on providers ' self‐reported global clinical behaviors OBJECTIVES Web-based learning has several potential advantages over lectures , such as anytime-anywhere access , rich multimedia , and nonlinear navigation . While known to be an effective method for learning facts , few studies have examined the effectiveness of Web-based formats for learning procedural skills . The authors sought to determine whether a Web-based tutorial is at least as effective as a didactic lecture for learning ultrasound-guided vascular access ( UGVA ) . METHODS Participating staff emergency physicians ( EPs ) and junior emergency medicine ( EM ) residents with no UGVA experience completed a precourse test and were r and omized to either a Web-based or a didactic group . The Web-based group was instructed to use an online tutorial and the didactic group attended a lecture . Participants then practice d on simulators and live models without any further instruction . Following a rest period , participants completed a four-station objective structured clinical examination ( OSCE ) , a written examination , and a postcourse question naire . Examination results were compared using a noninferiority data analysis with a 10 % margin of difference . RESULTS Twenty-one residents and EPs participated in the study . There were no significant differences in mean OSCE scores ( absolute difference = -2.8 % ; 95 % confidence interval [ CI ] = -9.3 % to 3.8 % ) or written test scores ( absolute difference = -1.4 % ; 95 % CI = -7.8 % to 5.0 % ) between the Web group and the didactic group . Both groups demonstrated similar improvements in written test scores ( 26.1 % vs. 25.8 % ; p = 0.95 ) . Ninety-one percent ( 10/11 ) of the Web group and 80 % ( 8/10 ) of the didactic group participants found the teaching format to be effective ( p = 0.59 ) . CONCLUSIONS Our Web-based tutorial was at least as effective as a traditional didactic lecture for teaching the knowledge and skills essential for UGVA . Participants expressed high satisfaction with this teaching technology . Web-based teaching may be a useful alternative to didactic teaching for learning procedural skills Objective To evaluate the effectiveness and costs of a multifaceted flexible educational programme aim ed at reducing antibiotic dispensing at the practice level in primary care . Design R and omised controlled trial with general practice s as the unit of r and omisation and analysis . Clinicians and research ers were blinded to group allocation until after r and omisation . Setting 68 general practice s with about 480 000 patients in Wales , United Kingdom . Participants 34 practice s were r and omised to receive the educational programme and 34 practice s to be controls . 139 clinicians from the intervention practice s and 124 from control practice s had agreed to participate before r and omisation . Practice level data covering all the clinicians in the 68 practice s were analysed . Interventions Intervention practice s followed the Stemming the Tide of Antibiotic Resistance ( STAR ) educational programme , which included a practice based seminar reflecting on the practice s ’ own dispensing and resistance data , online educational elements , and practising consulting skills in routine care . Control practice s provided usual care . Main outcome measures Total numbers of oral antibiotic items dispensed for all causes per 1000 practice patients in the year after the intervention , adjusted for the previous year ’s dispensing . Secondary outcomes included reconsultations , admissions to hospital for selected causes , and costs . Results The rate of oral antibiotic dispensing ( items per 1000 registered patients ) decreased by 14.1 in the intervention group but increased by 12.1 in the control group , a net difference of 26.1 . After adjustment for baseline dispensing rate , this amounted to a 4.2 % ( 95 % confidence interval 0.6 % to 7.7 % ) reduction in total oral antibiotic dispensing for the year in the intervention group relative to the control group ( P=0.02 ) . Reductions were found for all classes of antibiotics other than penicillinase-resistant penicillins but were largest and significant individually for phenoxymethylpenicillins ( penicillin V ) ( 7.3 % , 0.4 % to 13.7 % ) and macrolides ( 7.7 % , 1.1 % to 13.8 % ) . There were no significant differences between intervention and control practice s in the number of admissions to hospital or in reconsultations for a respiratory tract infection within seven days of an index consultation . The mean cost of the programme was £ 2923 ( € 3491 , $ 4572 ) per practice ( SD £ 1187 ) . There was a 5.5 % reduction in the cost of dispensed antibiotics in the intervention group compared with the control group ( −0.4 % to 11.4 % ) , equivalent to a reduction of about £ 830 a year for an average intervention practice . Conclusion The STAR educational programme led to reductions in all cause oral antibiotic dispensing over the subsequent year with no significant change in admissions to hospital , reconsultations , or costs . Trial registration IS RCT No 63355948 AIMS The aim of the study was to evaluate the effect of an e-learning educational program meant to foster the quality of drug prescription in hospitalized elderly patients . METHODS Twenty geriatric and internal medicine wards were r and omized to intervention ( e-learning educational program ) or control ( basic geriatric pharmacology notions ) . Logistic regression analysis was used in order to assess the effect of the intervention on the use of potentially inappropriate medication ( PIM , primary outcome ) at hospital discharge . Secondary outcomes were a reduced prevalence of at least one potential drug-drug interaction ( DDI ) and potentially severe DDI at discharge . Mortality rate and incidence of re-hospitalizations were other secondary outcomes assessed at the 12-month follow-up . RESULTS A total of 697 patients ( 347 in the intervention and 350 in the control arms ) were enrolled . No difference in the prevalence of PIM at discharge was found between arms ( OR 1.29 95%CI 0.87 - 1.91 ) . We also found no decrease in the prevalence of DDI ( OR 0.67 95%CI 0.34 - 1.28 ) and potentially severe DDI ( OR 0.86 95%CI 0.63 - 1.15 ) at discharge , nor in mortality rates and incidence of re-hospitalization at 12-month follow-up . CONCLUSIONS This e-learning educational program had no clear effect on the quality of drug prescription and clinical outcomes in hospitalized elderly patients . Given the high prevalence of PIMs and potential DDIs recorded in the frame of this study , other approaches should be developed in order to improve the quality of drug prescription in this population BACKGROUND AND PURPOSE An e-Learning programme appeared useful for providing training and information regarding a multi-centre image guided radiotherapy trial . The aim of this study is to demonstrate the utility of this e-Learning programme . MATERIAL S AND METHODS Modules were created on relevant pelvic anatomy , Cone Beam CT soft tissue recognition and trial details . Radiation therapist participants ' knowledge and confidence were evaluated before , at the end of , and after at least 6 weeks of e-Learning ( long term ) . RESULTS One hundred and eighty-five participants were recruited from 12 centres , with 118 in the first , and 67 in the second cohort . One hundred and forty-six participants had two tests ( pre and post e-Learning ) and 39 of these had three tests ( pre , post , and long term ) . There was an increase confidence after completion of modules ( p<0.001 ) . The first cohort pre scores increased from 67 ± 11 to 79 ± 8 ( p<0.001 ) post . The long term same question score was 73 ± 14 ( p=0.025 , comparing to pre-test ) , and different questions ' score was 77 ± 13 ( p=0.014 ) . In the second cohort , pre-test scores were 64 ± 10 , post-test same question score 78 ± 9 ( p<0.001 ) and different questions ' score 81 ± 11 ( p<0.001 ) . CONCLUSIONS e-Learning for a multi-centre clinical trial was feasible and improved confidence and knowledge BACKGROUND Each year , more than 1.5 million health care professionals receive advanced life support ( ALS ) training . OBJECTIVE To determine whether a blended approach to ALS training that includes electronic learning ( e-learning ) produces outcomes similar to those of conventional , instructor-led ALS training . DESIGN Open-label , noninferiority , r and omized trial . R and omization , stratified by site , was generated by Sealed Envelope ( Sealed Envelope , London , United Kingdom ) . ( International St and ardized R and omized Controlled Trial Number Register : ISCRTN86380392 ) SETTING 31 ALS centers in the United Kingdom and Australia . PARTICIPANTS 3732 health care professionals recruited between December 2008 and October 2010 . INTERVENTION A 1-day course supplemented with e-learning versus a conventional 2-day course . MEASUREMENTS The primary outcome was performance in a cardiac arrest simulation test at the end of the course . Secondary outcomes comprised knowledge- and skill-based assessment s , repeated assessment after remediation training , and re source use . RESULTS 440 of the 1843 participants r and omly assigned to the blended course and 444 of the 1889 participants r and omly assigned to conventional training did not attend the courses . Performance in the cardiac arrest simulation test after course attendance was lower in the electronic advanced life support ( e-ALS ) group compared with the conventional advanced life support ( c-ALS ) group ; 1033 persons ( 74.5 % ) in the e-ALS group and 1146 persons ( 80.2 % ) in the c-ALS group passed ( mean difference , -5.7 % [ 95 % CI , -8.8 % to -2.7 % ] ) . Knowledge- and skill-based assessment s were similar between groups , as was the final pass rate after remedial teaching , which was 94.2 % in the e-ALS group and 96.7 % in the c-ALS group ( mean difference , -2.6 % [ CI , -4.1 % to 1.2 % ] ) . Faculty , catering , and facility costs were $ 438 per participant for electronic ALS training and $ 935 for conventional ALS training . LIMITATIONS Many professionals ( 24 % ) did not attend the courses . The effect on patient outcomes was not evaluated . CONCLUSION Compared with conventional ALS training , an approach that included e-learning led to a slightly lower pass rate for cardiac arrest simulation tests , similar scores on a knowledge test , and reduced costs . PRIMARY FUNDING SOURCE National Institute of Health Research and Resuscitation Council ( UK ) |
798 | 12,499,451 | There is more evidence for the effectiveness of programmes based on providing personal support than environmental management to reduce stressors . | The effectiveness of current approaches to workplace stress management for nurses was assessed through a systematic review . | This study aim ed at exploring nurses ' views of the characteristics of severely demented patients , the difficulties these characteristics produced and the emotional reactions they evoked during the provision of care . Also , it aim ed at exploring any changes in these aspects during a year of regular systematic clinical supervision combined with the implementation of individualized care at an experimental ward ( EW ) ( n = 19 ) and at a control ward ( CW ) ( n = 19 ) . Data were collected by means of the Strain in Nursing Care scale , assessing the presence of certain characteristics in the patients , and how difficult each characteristic can be to h and le . The Emotional Reactions in Nursing Care scale was also used , assessing 18 pairs of emotions . The analysis showed that agitation , not being responsive and unruly behaviour were the most common features while emptiness and agony turned out to be the most difficult problems to h and le in the provision of care . Feelings of defeat and dissociation were reported to be almost as common as feelings of control and association . The EW nurses saw the patients as significantly more responsive , and victims of nihilation to a lesser degree and also patients ' willfulness and emptiness was significantly easier to h and le during the year of intervention . There were no significant changes on the CW . The mean values improved significantly in several aspects on the EW in comparison to the CW ; patients seen as victims of nihilation , easier to h and le agony , obediency , willfulness , evaluation and improved feelings of devotion and beneficence in the nurses . Thus the intervention seemed to improve the nurse-patient relationship and to decrease the experience of strain in the nurses The purpose of the study was to examine the effectiveness of assertiveness training in improving self-perceived levels of stress and assertiveness among nurses in Taiwan , Republic of China . The two-group experimental design was conducted in a 2,000-bed veteran general hospital . A sample of 60 volunteer Chinese-speaking nurses participated in the study . Subjects were r and omly assigned to one of two treatments : assertiveness training ( AT ) or alternate treatment control ( ATC ) , which served as a control and contained up date d knowledge of new computer technology for in patient setting s. Subjects in each group participated in six 2-hour workshops in the same two-week period . All subjects were pre- , post- , and follow-up posttested for stress and assertiveness with the Perceived Stress Scale ( PSS ) and Rathus Assertiveness Schedule ( RAS ) , respectively . Results revealed the following : ( 1 ) subjects in both groups of pretest were clearly subassertive and under considerable stress ; ( 2 ) by the end of training , the AT group scored significantly higher on the rating of assertiveness than those in the ATC group , and had successfully maintained their improvement by the 4-week follow-up ; and ( 3 ) by the end of training , the AT group reported significantly lower levels of stress than the ATC group as indicated on the PSS , and successfully maintained their improvements at the 4-week follow-up . Overall , the results indicate clear support for the effectiveness of assertiveness training for treating subassertive behaviors and stress in a population of professional nurses in Taiwan The usefulness of psychological training programs ( P.T.P. ) in health care setting s devoted to cancer care is beginning to be recognised but their content , form and effectiveness need further investigation . Seventy-two oncology nurses were r and omly assigned to a 24-h P.T.P. or to a waiting list period . Attitudes were assessed by a semantic differential question naire , occupational stress was assessed by the Nursing Stress Scale and communication skills were assessed by st and ardised videotaped role-playing exercises . These were used to compare trained ( T.S. ) and control subjects ( C.S. ) . The results show a significant training effect on attitudes ( P = 0.05 ) , especially on those related to self concept ( P = 0.004 ) , and on the level of occupational stress related to inadequate preparation ( P = 0.02 ) . Limited changes were found regarding post-training communication skills . T.S. were significantly more in control of the interview than C.S. ( P = 0.02 ) . The results indicate that 24-h P.T.P. assessed here are effective . The data also demonstrate the need to consoli date the skills acquired by regular post-training sessions The aim of this study was to study creativity and innovative climate , tedium and burnout among the nurses on two wards during 1 year of systematic clinic supervision combined with the implementation of individualized care on an experimental ward ( EW ) for severely demented patients , as compared with a similar control ward ( CW ) . EW nurses had systematic clinic supervision and each patient had his/her nursing care carefully planned , documented and evaluated . The intervention was evaluated by means of the Creative Climate Question naire , Burnout Measure and the Maslach Burnout Inventory . Creativity and innovative climate improved significantly among the EW nurses ( n = 19 ) in eight out of 10 factors during the year of intervention while there was no change on the control ward ( n = 20 ) . Tedium and burnout decreased significantly among the EW nurses while no change was seen in this respect among the CW nurses . It seems reasonable to assume that systematic clinical supervision and individualized planned care decreases the negative outcome of stress caused by the psychological burden imposed by nursing care . It also increases nurses ' creativity , which , in turn , may benefit patient care . The findings of this study point to the necessity for a support system that focuses on the work itself , i.e. the nursing care . Individualized planned care and systematic clinical supervision may offer this kind of support This study was set up to test the effectiveness of primary nursing on the burnout level of psychiatric nurses . It was expected that , under certain conditions , such as a primary nursing care delivery with an adequate feedback system , the burnout level would decrease . In a quasi-experimental research design , a cohort of 161 psychiatric nurses was followed for 2.5 years . Results showed that although the burnout level did not change as a result of primary nursing , psychiatric nurses and the practical nurses seemed able to work according to the principles of primary nursing . Strong indications were found that the job turnover decreased as a result of the introduction of primary nursing . Because two main problems were encountered in this study , a high drop-out due to job turnover among nurses and the imitation of the intervention by the control group , several additional analyses were performed The purpose of this study was to test the effectiveness of relaxation training , which was based on the cognitive-behavioral model and specifically focused on helping Chinese registered nurses employed in large teaching hospitals to reduce their work stress in Taiwan , Republic of China . The study design was a pretest-posttest control design with two posttest points . The 137 subjects were selected r and omly from three first-ranked teaching hospitals . Twenty-three subjects in the experimental group and 23 in the control group from each hospital participated in the study . The treatment of the experimental group consisted of two sessions of relaxation training based on Smith 's ( 1988 ) cognitive behavioral model of relaxation at weeks 1 and 2 , with a follow-up session in the fifth week . The control group had the same sequence of sessions with a presentation by the research er on theory analysis in nursing . The mean scores on the Nurse Stress Checklist ( NSC ) and the Chinese General Health Question naire ( CGHQ ) differed significantly between the experimental and control group in posttest 2 at week 5 . These results supported the hypotheses that the relaxation training decreased the Chinese nurses ' self-reported work stress as measured by NSC and increased the Chinese nurses ' self-reported psychophysiologic health as measured by CGHQ . The significant difference on means of the CGHQ in posttest 1 at week 2 showed that the self-reported psychophysiologic health level responded to the relaxation training earlier than to the self-reported work stress level . In the relaxation treatment , duration of practice was an important factor of the effectiveness of the treatment on the dependent variable of NSC . It is suggested that even brief teaching of relaxation techniques may reduce work stress levels and promote a sense of psychophysiologic health in Chinese nurses who are employed in large teaching hospitals in Taiwan |
799 | 28,658,668 | In summary , miR-20b , 21 , 106b , 125a , 137 , 141 , 145 , 146a , 196a , 196b , 206 , 214 , 218 , 451 , 486 - 5p and 506 demonstrate significantly prognostic value .
Among them , miR-20b , 125a , 137 , 141 , 146a , 196a , 206 , 218 , 486 - 5p and 506 are strong biomarkers of prognosis in GC | BACKGROUND Previous articles have reported that expression levels of microRNAs ( miRNAs ) are associated with survival time of patients with gastric cancer ( GC ) .
A systematic review and meta- analysis was performed to study the outcome of it . | Purpose To investigate the potential c and i date microRNA ( miRNA ) biomarkers for the clinical diagnosis , classification , and prognosis of gastric cancer ( GC ) . Methods We use bioinformatics overlapping subclasses analysis to find the tumor grade and lymphatic metastasis-related GC specific miRNAs from the Cancer Genome Atlas ( TCGA ) data base . Then , we further investigated these GC specific miRNAs distributions in different GC clinical features and their correlations overall survival on the basis of GC patients ’ information and their related RNA sequencing profile from TCGA . Finally , we r and omly selected some of key miRNAs use qRT-PCR to confirm the reliability and validity . Results 22 GC specific key miRNAs were identified ( Fold-change > 2 , P < 0.05 ) , 11 of them were discriminatively expressed with tumor size , grade , TNM stage and lymphatic metastasis ( P < 0.05 ) . In addition , nine miRNAs ( miR-196b-5p , miR-135b-5p , miR-183 - 5p , miR-182 - 5p , miR-133a-3p , miR-486 - 5p , miR-144 - 5p , miR-129 - 5p and miR-145 - 5p ) were found to be significantly associated with overall survival ( log-rank P < 0.05 ) . Finally , four key miRNAs ( miR-183 - 5p , miR-486 - 5p , miR-30c-2 - 3p and miR-133a-3p ) were r and omly selected to validation and their expression levels in 53 newly diagnosed GC patients by qRT-PCR . Results showed that the fold-changes between TCGA and qRT-PCR were 100 % in agreement . We also found miR-183 - 5p and miR-486 - 5p were significantly correlated with tumor TNM stage ( P < 0.05 ) , and miR-30c-2 - 3p and miR-133a-3p were associated with tumor differentiation degree and lymph-node metastasis ( P < 0.05 ) . These verified miRNAs clinical ly relevant , and the bioinformatics analysis results were almost the same . Conclusion These key miRNAs may functions as potential c and i date biomarkers for the clinical diagnosis , classification and prognosis for GC Background MicroRNAs are aberrantly expressed and correlate with tumourigenesis and the progression of solid tumours . The miR-200 family determines the epithelial phenotype of cancer cells and regulates invasiveness and migration . Thus , we hypothesised that the quantitative detection of the miR-200 family as epithelial-specific microRNAs in the blood could be a useful clinical biomarker for gastric cancer ( GC ) . Methods We initially vali date d the expression levels of miR-200a , 200b , 200c and 141 in GC cell lines ( n = 2 ) and blood from healthy controls ( n = 19 ) using real-time quantitative reverse transcription PCR ( qRT-PCR ) . The microarray expression profiles of the miR-200 family in 160 paired sample s of non-tumour gastric mucosae and GC were downloaded through ArrayExpress and analysed . MiR-200c was selected for clinical validation . The qRT-PCR prospect i ve assessment of miR-200c was performed using 67 blood sample s ( 52 stage I-IV GC patients and 15 controls ) ; the area under the receiver operating characteristic curve ( AUC-ROC ) was estimated . The Kaplan-Meier and Breslow-Wilcoxon tests were used to assess the correlation of miR-200c with overall and progression-free survival ( OS and PFS ) . Multivariate analyses were performed using the Cox model . Results The miR-200c blood expression levels in GC patients were significantly higher than in normal controls ( p = 0.018 ) . The AUC-ROC was 0.715 ( p = 0.012 ) . The sensitivity , specificity and accuracy rates of 65.4 % , 100 % and 73.1 % , respectively , were observed . The levels of miR-200c in the blood above the cutoff defined by the ROC curve was found in 17.6 % of stage I-II GC patients , 20.6 % of stage III patients and 67.7 % of stage IV patients ( p < 0.001 ) . The miR-200c expression levels were not associated with clinical or pathological characteristics or recent surgical procedures . There was a correlation ( p = 0.016 ) with the number of lymph node metastases and the increased expression levels of miR-200c in blood were significantly associated with a poor OS ( median OS , 9 vs 24 months ; p = 0.016 ) and PFS ( median PFS , 4 vs 11 months ; p = 0.044 ) . Multivariate analyses confirmed that the upregulation of miR-200c in the blood was associated with OS ( HR = 2.24 ; p = 0.028 ) and PFS ( HR = 2.27 ; p = 0.028 ) , independent of clinical covariates . Conclusions These data suggest that increased miR-200c levels are detected in the blood of gastric cancer patients . MiR-200c has the potential to be a predictor of progression and survival The occurrence of lymph node metastases ( LNM ) after endoscopic submucosal dissection ( ESD ) in patients with gastric cancer ( GC ) leads to poor prognosis . However , few biomarkers are available to predict LNM in GC patients . Thus , we measured expression of 6 cancer-related miRNAs using real-time RT-PCR in 102 GC sample s that were r and omized into a training set and a testing set ( each , 51 cases ) . Using logistic regression , we identified 4-miRNA ( miR-27b , miR-128 , miR-100 and miR-214 ) signatures for predicting LNM in GC patients . Patients with high-risk scores for the 4-miRNA signature tended to have higher LNM than those with low-risk scores . Meanwhile , the ROC curve of the 4-miRNA signature was better for predicting LNM in GC patients . In addition , Cox regression analysis indicated that a 2-miRNA signature ( miR-27b and miR-214 ) or a miR-214/N stage signature was predictive of survival for GC patients . This work describes a previously unrecognized 4-miRNA signature involved in LNM and a 2-miRNA signature or miR-214/N stage signature related to GC patients ’ survival |
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